Doxorubicin

Identification

Summary

Doxorubicin is a medication used to treat various cancers, including AIDS-associated Kaposi's Sarcoma and metastatic cancers.

Brand Names

Adriamycin, Doxil, Myocet

Generic Name

Doxorubicin

DrugBank Accession Number

DB00997

Background

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius along side with daunorubicin, another cytotoxic agent, in 1970.^3,39,31 Although they both have aglyconic and sugar moieties, doxorubicin's side chain terminates with a primary alcohol group compared to the methyl group of daunorubicin.³⁹ Although its detailed molecular mechanisms have yet to be understood, doxorubicin is generally thought to exert its effect through DNA intercalation, which eventually leads to DNA damage and the generation of reactive oxygen species.³¹ Thanks to its efficacy and broad effect, doxorubicin was approved by the FDA in 1974 to treat a variety of cancer, including but not limited to breast, lung, gastric, ovarian, thyroid, non-Hodgkin’s and Hodgkin’s lymphoma, multiple myeloma, sarcoma, and pediatric cancers.^1,31,42 However, one of the major side effects of doxorubicin is cardiotoxicity, which excludes patients with poor heart function and requires treatment termination once the maximally tolerated cumulative dose is reached.⁴⁰

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 543.5193
Monoisotopic: 543.174060775
Chemical Formula: C₂₇H₂₉NO₁₁

Synonyms

(1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
(8S-cis)-10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione
14-hydroxydaunomycin
14-hydroxydaunorubicine
Doxorubicin
Doxorubicin nanoparticles
Doxorubicina
Doxorubicine
Doxorubicinum
Hydroxydaunorubicin
MTC-DOX
MTC-DOX for Injection

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

Doxorubicin is indicated for the treatment of neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin and non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor, metastatic neuroblastoma, metastatic soft tissue and bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma.⁴² Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.⁴² For the liposomal formulation, doxorubicin is indicated for the treatment of ovarian cancer that has progressed or recurred after platinum-based chemotherapy, AIDS-Related Kaposi's Sarcoma after the failure of prior systemic chemotherapy or intolerance to such therapy, and multiple myeloma in combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy.⁴¹

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Patient Characteristics	Dose Form
Treatment of	Aids-related kaposi's sarcoma		••••••••••••	•••••••• •••••••• •••••••••• •••• •••••••••• ••••• •••• •••• •• ••••• •• •••••••	••••••••••• •••••••••
Treatment of	Aids-related kaposi's sarcoma		••••••••••••	••••••• •• •• ••••• ••• ••••• •••••••• •••••••• •••••••••• •• ••••••••••• •• ••••• •••••••	••••••••••• •••••••••• •••••••••• ••••••••••• •••••••••
Treatment of	Acute lymphoblastic leukemia (all)		••••••••••••		•••••••••• •••••••••• ••••••• •••••••••••• ••• ••••••••
Treatment of	Acute myeloid leukemia		••••••••••••		•••••••••• •••••••••• ••••••• •••••••••••• ••• ••••••••
Used in combination to treat	Advanced endometrial cancer	Regimen in combination with: Cisplatin (DB00515)	••• •••••

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Doxorubicin is a cytotoxic, cell-cycle non-specific anthracycline antibiotic.^2,37 It is generally thought to exert its antitumor effect by destabilizing DNA structures through intercalation, thus introducing DNA strand breakages and damages.^34,35,37 Not only does it alter the transcriptomes of the cells, failure in repairing DNA structures can also initiate the apoptotic pathways.^37,38 Additionally, doxorubicin intercalation can also interfere with vital enzyme activity, such as topoisomerase II, DNA polymerase, and RNA polymerase, leading to cell cycle arrests.³⁷ Finally, doxorubicin can also generate cytotoxic reactive oxygen species to exert cellular damages.²⁹

Mechanism of action

Generally, doxorubicin is thought to exert its antineoplastic activity through 2 primary mechanisms: intercalation into DNA and disrupt topoisomerase-mediated repairs and free radicals-mediated cellular damages.³¹

Doxorubicin can intercalate into DNA through the anthraquinone ring, which stabilizes the complex by forming hydrogen bonds with DNA bases.³³ Intercalation of doxorubicin can introduce torsional stress into the polynucleotide structure, thus destabilizing nucleosome structures and leading to nucleosome eviction and replacement.^34,35 Additionally, the doxorubicin-DNA complex can interfere with topoisomerase II enzyme activity by preventing relegation of topoisomerase-mediated DNA breaks, thus inhibiting replication and transcription and inducing apoptosis.^36,37

Moreover, doxorubicin can be metabolized by microsomal NADPH-cytochrome P-450 reductase into a semiquinone radical, which can be reoxidized in the presence of oxygen to form oxygen radicals.^7,29 Reactive oxygen species have been known to cause cellular damage through various mechanisms, including lipid peroxidation and membrane damage, DNA damage, oxidative stress, and apoptosis.³² Although free radicals generated from this pathway can be deactivated by catalase and superoxide dismutase, tumor and myocardial cells tend to lack these enzymes, thus explaining doxorubicin's effectiveness against cancer cells and tendency to cause cardiotoxicity.^7,29,6

Target	Actions	Organism
ADNA topoisomerase 2-alpha	inhibitor	Humans
ADNA	intercalation	Humans
UNucleolar and coiled-body phosphoprotein 1	Not Available	Humans
ADNA topoisomerase 1	inhibitor	Humans
ADNA topoisomerase 2-beta	inhibitor	Humans

Absorption

Following a 10 mg/m² administration of liposomal doxorubicin in patients with AIDS-related Kaposi's Sarcoma, the C_max and AUC values were calculated to be 4.12 ± 0.215 μg/mL and 277 ± 32.9 μg/mL•h respectively.⁴¹

Volume of distribution

The steady-state distribution volume of doxorubicin ranges from 809 L/m² to 1214 L/m².⁴²

Protein binding

The binding of doxorubicin and its major metabolite, doxorubicinol, to plasma proteins is 75% and is independent of plasma concentration of doxorubicin up to 1.1 µg/mL. Doxorubicin does not cross the blood-brain barrier.⁴² Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined.⁴¹

Metabolism

Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged.⁶

The two-electron reduction is the major metabolic pathway of doxorubicin.⁶ In this pathway, doxorubicin is reduced to doxorubicinol, a secondary alcohol, by various enzymes, including Alcohol dehydrogenase [NADP(+)], Carbonyl reductase NADPH 1, Carbonyl reductase NADPH 3, and Aldo-keto reductase family 1 member C3.^{19,20,6,21,22}

The one-electron reduction is facilitated by several oxidoreductase, both cytosolic and mitochondrial, to form a doxirubicin-semiquinone radical.⁷ These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases.^{23,24,25,26,27,28} This semiquinone metabolite can be re-oxidized to doxorubicin, although with the concurrent formation of reactive oxygen species (ROS) and hydrogen peroxide.²⁹ It is the ROS generating through this pathway that contributes most to the doxorubicin-related adverse effects, particularly cardiotoxicity, rather than through doxorubicin semiquinone formation.³⁰

Deglycosidation is a minor metabolic pathway, since it only accounts for 1 to 2% of doxorubicin metabolism.^6,15 Under the catalysis of cytoplasmic NADPH quinone dehydrogenase, xanthine oxidase, NADPH-cytochrome P450 reductase, doxorubicin can either be reduced to doxorubicin deoxyaglycone or hydrolyzed to doxorubicin hydroxyaglycone.^16,17,18

Hover over products below to view reaction partners

Doxorubicin

Route of elimination

Approximately 40% of the dose appears in the bile in 5 days, while only 5% to 12% of the drug and its metabolites appear in the urine during the same time period. In urine, <3% of the dose was recovered as doxorubicinol over 7 days.⁴²

Half-life

The terminal half-life of doxorubicin ranges from 20 hours to 48 hours.⁴² The distribution half-life of doxorubicin is approximately 5 minutes.⁴² For the liposomal formulation, the first-phase and second-phase half-lives were calculated to be 4.7 ± 1.1 and 52.3 ± 5.6 hours respectively for a 10 mg/m² of doxorubicin in patients with AIDS-Related Kaposi’s Sarcoma.⁴¹

Clearance

The plasma clearance of doxorubicin ranges from 324 mL/min/m2 to 809 mL/min/m² by metabolism and biliary excretion.⁴² Sexual differences in doxorubicin were also observed, with men having a higher clearance compared to women (1088 mL/min/m² versus 433 mL/min/m²).⁴² Following the administration of doses ranging from 10 mg/m2 to 75 mg/m² of doxorubicin hydrochloride, the plasma clearance was estimated to be 1540 mL/min/m² in children greater than 2 years of age and 813 mL/min/m² in infants younger than 2 years of age.⁴²

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

Doxorubicin hydrochloride treatment can increase the risk of secondary malignancies based on postmarketing reports. Doxorubicin hydrochloride was mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay.⁴²

Doxorubicin hydrochloride decreased fertility in female rats at doses of 0.05 and 0.2 mg/kg/day (approximately 0.005 and 0.02 times the recommended human dose, based on body surface area).⁴² In females of reproductive potential, Doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment.⁴²

A single intravenous dose of 0.1 mg/kg doxorubicin hydrochloride (approximately 0.01 times the recommended human dose based on body surface area) was toxic to male reproductive organs in animal studies, producing testicular atrophy, diffuse degeneration of the seminiferous tubules, and oligospermia/hypospermia in rats. Doxorubicin hydrochloride induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice.⁴²

Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection/for Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection/for Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2. Advise pregnant women of the potential risk to a fetus.⁴²

Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride. Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary.⁴²

Pathways

Pathway	Category
Doxorubicin Metabolism Pathway	Drug metabolism

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Retinoic acid receptor gamma	---	(C;C) / (C;T)	C>T	ADR Directly Studied	Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.	Details
Solute carrier family 28 member 3	---	(A;A) / (A;G)	G > A	ADR Directly Studied	Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.	Details
UDP-glucuronosyltransferase 1-6	UGT1A6*4	(T;T) / (G;T)	G > T	ADR Directly Studied	Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.	Details

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Integrate drug-drug interactions in your software
Abametapir	The serum concentration of Doxorubicin can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Doxorubicin can be increased when combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Doxorubicin.
Abiraterone	The serum concentration of Doxorubicin can be increased when it is combined with Abiraterone.

Food Interactions

Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of doxorubicin.
Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of doxorubicin.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Doxorubicin citrate	AJQ2ZNG2WL	111266-55-8	INEKNBHAPBIAFK-RUELKSSGSA-N
Doxorubicin hydrochloride	82F2G7BL4E	25316-40-9	MWWSFMDVAYGXBV-RUELKSSGSA-N

International/Other Brands

Adriablastina (Pfizer) / Adriblastin (Actavis)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Adriamycin PFS	Solution	2 mg / mL	Intravenous; Intravesical	Pfizer Canada Ulc	1995-12-31	Not applicable
Adriamycin Rdf	Powder, for solution	10 mg / vial	Intravenous	Pfizer Canada Ulc	1996-12-31	2006-08-02
Adriamycin Rdf	Powder, for solution	150 mg / vial	Intravenous	Pfizer Canada Ulc	1996-12-31	2006-08-02
Adriamycin Rdf	Powder, for solution	50 mg / vial	Intravenous	Pfizer Canada Ulc	1995-12-31	2006-08-02
Adriamycin Rdf Inj 10mg/vial	Powder, for solution	10 mg / vial	Intravenous	Carlo Erba Farmitalia Spa	1976-12-31	1996-09-10

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Adriamycin	Injection, solution	2 mg/1mL	Intravenous	Hikma Pharmaceuticals USA Inc.	1996-05-01	Not applicable
Adriamycin	Injection, powder, lyophilized, for solution	2 mg/1mL	Intravenous	Hikma Pharmaceuticals USA Inc.	2018-01-19	Not applicable
Adriamycin	Injection, solution	2 mg/1mL	Intravenous	Hikma Pharmaceuticals USA Inc.	1996-05-01	Not applicable
Adriamycin	Injection, powder, lyophilized, for solution	2 mg/1mL	Intravenous	Bedford Pharmaceuticals	1996-05-01	2014-06-30
Adriamycin	Injection, solution	2 mg/1mL	Intravenous	Bedford Pharmaceuticals	1996-05-01	2014-06-30

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Doxorubicin Hydrochloride	Doxorubicin hydrochloride (2 mg/1mL)	Injection, powder, lyophilized, for solution	Intra-arterial; Intravenous; Intravesical	Hospira, Inc.	2016-04-18	2017-12-31
doxorubicin hydrochloride, Liposomal	Doxorubicin hydrochloride (2 mg/1mL)	Injection, suspension, liposomal	Intravenous	Baxter Healthcare Corporation	2023-12-19	Not applicable
Lipodox	Doxorubicin hydrochloride (2 mg/1mL)	Injectable, liposomal	Intravenous	Sun Pharmaceutical Industries, Inc.	2012-02-09	2015-05-29
Lipodox 50	Doxorubicin hydrochloride (2 mg/1mL)	Injectable, liposomal	Intravenous	Sun Pharmaceutical Industries, Inc.	2012-02-09	2015-05-29

Chemical Identifiers

UNII: 80168379AG
CAS number: 23214-92-8
InChI Key: AOJJSUZBOXZQNB-TZSSRYMLSA-N
InChI: InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
IUPAC Name: (8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
SMILES: COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O

References

Synthesis Reference

Gian P. Vicario, Sergio Penco, Federico Arcamone, "Daunorubicin and doxorubicin labelled with .sup.14 C at the 14-position and processes for their preparation." U.S. Patent US4211864, issued March, 1976.

US4211864

General References

Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. [Article]
Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA: Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. [Article]
Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101-10. [Article]
Di Marco A, Gaetani M, Scarpinato B: Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969 Feb;53(1):33-7. [Article]
Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR: Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. J Bacteriol. 1999 Jan;181(1):305-18. [Article]
Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72. [Article]
Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8. [Article]
Quereux G, Marques S, Nguyen JM, Bedane C, D'incan M, Dereure O, Puzenat E, Claudy A, Martin L, Joly P, Delaunay M, Beylot-Barry M, Vabres P, Celerier P, Sasolas B, Grange F, Khammari A, Dreno B: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sezary syndrome. Arch Dermatol. 2008 Jun;144(6):727-33. doi: 10.1001/archderm.144.6.727. [Article]
Ansell SM, Kyle RA, Reeder CB, Fonseca R, Mikhael JR, Morice WG, Bergsagel PL, Buadi FK, Colgan JP, Dingli D, Dispenzieri A, Greipp PR, Habermann TM, Hayman SR, Inwards DJ, Johnston PB, Kumar SK, Lacy MQ, Lust JA, Markovic SN, Micallef IN, Nowakowski GS, Porrata LF, Roy V, Russell SJ, Short KE, Stewart AK, Thompson CA, Witzig TE, Zeldenrust SR, Dalton RJ, Rajkumar SV, Gertz MA: Diagnosis and management of Waldenstrom macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines. Mayo Clin Proc. 2010 Sep;85(9):824-33. doi: 10.4065/mcp.2010.0304. Epub 2010 Aug 11. [Article]
Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC Jr, Creasman W, Yordan E: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer. 1985 Apr 15;55(8):1648-53. doi: 10.1002/1097-0142(19850415)55:8<1648::aid-cncr2820550806>3.0.co;2-7. [Article]
Liu W, Yang M, Ping L, Xie Y, Wang X, Zhu J, Song Y: Chemotherapy with a Pegylated Liposomal Doxorubicin-Containing Regimen in Newly Diagnosed Hodgkin Lymphoma Patients. Cardiovasc Toxicol. 2021 Jan;21(1):12-16. doi: 10.1007/s12012-020-09589-z. Epub 2020 Jul 18. [Article]
Yokoi K, Matsuguma H, Nakahara R, Kondo T, Kamiyama Y, Mori K, Miyazawa N: Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol. 2007 Jan;2(1):73-8. doi: 10.1097/JTO.0b013e31802bafc8. [Article]
Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N: Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. doi: 10.1001/jamaoncol.2019.0001. [Article]
Escobar PF, Markman M, Zanotti K, Webster K, Belinson J: Phase 2 trial of pegylated liposomal doxorubicin in advanced endometrial cancer. J Cancer Res Clin Oncol. 2003 Nov;129(11):651-4. doi: 10.1007/s00432-003-0497-8. Epub 2003 Sep 23. [Article]
Licata S, Saponiero A, Mordente A, Minotti G: Doxorubicin metabolism and toxicity in human myocardium: role of cytoplasmic deglycosidation and carbonyl reduction. Chem Res Toxicol. 2000 May;13(5):414-20. doi: 10.1021/tx000013q. [Article]
Lin SR, Lin CS, Chen CC, Tseng FJ, Wu TJ, Weng L, Weng CF: Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells. Mol Cell Biochem. 2020 Dec;475(1-2):119-126. doi: 10.1007/s11010-020-03864-x. Epub 2020 Aug 4. [Article]
Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [Article]
Gutierrez PL, Gee MV, Bachur NR: Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75. [Article]
Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]
Mordente A, Minotti G, Martorana GE, Silvestrini A, Giardina B, Meucci E: Anthracycline secondary alcohol metabolite formation in human or rabbit heart: biochemical aspects and pharmacologic implications. Biochem Pharmacol. 2003 Sep 15;66(6):989-98. doi: 10.1016/s0006-2952(03)00442-8. [Article]
Bains OS, Karkling MJ, Lubieniecka JM, Grigliatti TA, Reid RE, Riggs KW: Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. J Pharmacol Exp Ther. 2010 Mar;332(3):755-63. doi: 10.1124/jpet.109.160614. Epub 2009 Dec 9. [Article]
Novotna R, Wsol V, Xiong G, Maser E: Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6. doi: 10.1016/j.toxlet.2008.06.858. Epub 2008 Jun 21. [Article]
Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]
Gustafson DL, Swanson JD, Pritsos CA: Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. Cancer Commun. 1991 Sep;3(9):299-304. doi: 10.3727/095535491820873038. [Article]
Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]
Minotti G, Recalcati S, Mordente A, Liberi G, Calafiore AM, Mancuso C, Preziosi P, Cairo G: The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium. FASEB J. 1998 May;12(7):541-52. doi: 10.1096/fasebj.12.7.541. [Article]
Miyamoto Y, Koh YH, Park YS, Fujiwara N, Sakiyama H, Misonou Y, Ookawara T, Suzuki K, Honke K, Taniguchi N: Oxidative stress caused by inactivation of glutathione peroxidase and adaptive responses. Biol Chem. 2003 Apr;384(4):567-74. doi: 10.1515/BC.2003.064. [Article]
Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, Altman RB: Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 2011 Jul;21(7):440-6. doi: 10.1097/FPC.0b013e32833ffb56. [Article]
Doroshow JH: Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4514-8. doi: 10.1073/pnas.83.12.4514. [Article]
Chaires JB, Satyanarayana S, Suh D, Fokt I, Przewloka T, Priebe W: Parsing the free energy of anthracycline antibiotic binding to DNA. Biochemistry. 1996 Feb 20;35(7):2047-53. doi: 10.1021/bi952812r. [Article]
Yang F, Kemp CJ, Henikoff S: Doxorubicin enhances nucleosome turnover around promoters. Curr Biol. 2013 May 6;23(9):782-7. doi: 10.1016/j.cub.2013.03.043. Epub 2013 Apr 18. [Article]
Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, Neefjes J: Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun. 2013;4:1908. doi: 10.1038/ncomms2921. [Article]
Jawad B, Poudel L, Podgornik R, Steinmetz NF, Ching WY: Molecular mechanism and binding free energy of doxorubicin intercalation in DNA. Phys Chem Chem Phys. 2019 Feb 13;21(7):3877-3893. doi: 10.1039/c8cp06776g. [Article]
Tacar O, Sriamornsak P, Dass CR: Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2013 Feb;65(2):157-70. doi: 10.1111/j.2042-7158.2012.01567.x. Epub 2012 Aug 2. [Article]
Stamm P, Kirmes I, Palmer A, Molitor M, Kvandova M, Kalinovic S, Mihalikova D, Reid G, Wenzel P, Munzel T, Daiber A, Jansen T: Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function. Life Sci. 2021 Nov 1;284:119879. doi: 10.1016/j.lfs.2021.119879. Epub 2021 Aug 11. [Article]
Carvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, Moreira PI: Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16(25):3267-85. doi: 10.2174/092986709788803312. Epub 2009 Sep 1. [Article]
van der Zanden SY, Qiao X, Neefjes J: New insights into the activities and toxicities of the old anticancer drug doxorubicin. FEBS J. 2021 Nov;288(21):6095-6111. doi: 10.1111/febs.15583. Epub 2020 Oct 19. [Article]
FDA Approved Drug Products: DOXIL (doxorubicin hydrochloride) liposome injection, for intravenous use [Link]
FDA Approved Drug Products: DOXORUBICIN HYDROCHLORIDE injection, for intravenous use [Link]
EMA Approved Drug Products: Celdoxome (Doxorubicin hydrochloride) pegylated liposomal for intravenous use [Link]
Doxorubicin Hydrochloride Pfizer MSDS [Link]
Doxorubicin Hydrochloride Cayman Chemical MSDS [Link]
FDA Approved Drug Products: DOXORUBICIN HYDROCHLORIDE injection, powder, lyophilized, for solution [Link]
FDA Approved Drug Products: DOXORUBICIN HYDROCHLORIDE injection, suspension, liposomal [Link]

External Links

Human Metabolome Database: HMDB0015132
KEGG Drug: D03899
KEGG Compound: C01661
PubChem Compound: 31703
PubChem Substance: 46507641
ChemSpider: 29400
BindingDB: 32022
RxNav: 3639
ChEBI: 28748
ChEMBL: CHEMBL53463
ZINC: ZINC000003918087
Therapeutic Targets Database: DNC000163
PharmGKB: PA449412
PDBe Ligand: DM2
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Doxorubicin

PDB Entries

151d / 1d12 / 1da9 / 1i1e / 1p20 / 2dr6 / 4dx7 / 4zvm / 5mra / 5om7 …

show 3 more

FDA label

Download (105 KB)

MSDS

Download (74.1 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Safety and Efficacy	1
4	Completed	Health Services Research	Breast Cancer	1
4	Completed	Other	Breast Cancer / Obesity	1
4	Completed	Other	Hepatocellular Carcinoma	1
4	Completed	Prevention	Carcinoma of Urinary Bladder, Superficial	1

Pharmacoeconomics

Manufacturers

Ortho biotech products lp
Pharmacia and upjohn co
App pharmaceuticals llc
Bedford laboratories div ben venue laboratories inc
Pharmachemie bv
Teva parenteral medicines inc
Bristol myers squibb co

Packagers

Alza Corp.
APP Pharmaceuticals
APPD
Baxter International Inc.
Bedford Labs
Ben Venue Laboratories Inc.
Bristol-Myers Squibb Co.
Centocor Ortho Biotech Inc.
Mead Johnson and Co.
Pfizer Inc.
Pharmachemie BV
Pharmacia Inc.
Schering-Plough Inc.
Sopherion Therapeutics LLC
Teva Pharmaceutical Industries Ltd.

Dosage Forms

Form	Route	Strength
Injection, solution	Parenteral	50 MG
Injection, powder, lyophilized, for solution	Intravenous	2 mg/1mL
Injection, powder, for solution	Intravenous
Injection	Intravenous	2 mg/ml
Powder, for solution	Intravenous	10 mg / vial
Injection	Parenteral	10 mg
Injection	Parenteral	200 mg
Injection	Parenteral	50 mg
Injection, powder, for solution	Parenteral	50 mg
Injection, powder, for solution		10 MG/5ML
Injection, powder, for solution		50 MG
Injection, solution	Intravenous; Parenteral	10 MG/5ML
Injection, solution	Intravenous; Parenteral	200 MG/100ML
Injection, solution	Intravenous; Parenteral	50 MG/25ML
Injection	Parenteral	2 mg
Solution	Intravenous	10.0 mg
Injection	Intravenous
Injection, solution	Intravenous	2 MG/ML
Solution	Parenteral	10 mg
Solution	Parenteral	200 mg
Solution	Parenteral	50 mg
Injection, powder, lyophilized, for solution		10 mg
Injection, powder, lyophilized, for solution		50 mg
Solution	Parenteral	2 MG/ML
Suspension	Intravenous	2 mg / mL
Injectable, liposomal; injection; solution	Intravenous	2 mg/ml
Injection	Intravenous	2.00 mg/ml
Solution	Intravenous	2 mg/ml
Injectable, liposomal	Intravenous	2 MG/ML
Injection, powder, lyophilized, for solution	Parenteral	10 mg
Injection, solution	Intravenous; Intravesical	2 mg/ml
Injection, powder, lyophilized, for solution	Intravenous	10 mg
Injection, powder, lyophilized, for solution	Intravenous	50 mg
Injectable, liposomal	Intravenous	2 mg/1mL
Injection, suspension, liposomal	Intravenous	2 mg/1mL
Injection, suspension, liposomal	Intravitreal	2 mg/1mL
Injection, solution	Parenteral	10 MG
Injection, solution	Parenteral	150 MG
Solution	Intravenous; Intravesical	2 mg/ml
Suspension	Intravenous	2.000 mg
Injection, solution, concentrate	Intravenous	2 mg/ml
Powder	Parenteral	50 MG
Injection	Parenteral	2 mg/ml
Solution	Intravenous; Intravesical	50 mg
Solution	Intravenous	10 mg/5ml
Solution	Intravenous	50 mg/25ml
Powder, for solution	Intravenous	150 mg / vial
Powder, for solution	Intravenous	50 mg / vial
Injection, solution	Parenteral	2 MG/ML
Injection, solution	Parenteral	200 MG
Injection	Intravenous	10 mg/5mL
Injection	Intravenous	2 mg/1mL
Injection	Intravenous	20 mg/10mL
Injection	Intravenous	200 mg/100mL
Injection	Intravenous	50 mg/25mL
Injection, powder, lyophilized, for solution	Intra-arterial; Intravenous; Intravesical	2 mg/1mL
Injection, powder, lyophilized, for solution	Intravenous	10 mg/1
Injection, powder, lyophilized, for solution	Intravenous	150 mg/1
Injection, powder, lyophilized, for solution	Intravenous	20 mg/1
Injection, powder, lyophilized, for solution	Intravenous	50 mg/1
Injection, solution	Intravenous	2 mg/1mL
Powder, for solution	Intravenous; Intravesical	10 mg / vial
Powder, for solution	Intravenous; Intravesical	150 mg / vial
Powder, for solution	Intravenous; Intravesical	50 mg / vial
Solution	Intravenous	2 mg / mL
Solution	Intravenous; Intravesical	2 mg / mL
Injection, powder, lyophilized, for solution	Parenteral	100 mg
Injection, powder, lyophilized, for solution	Intravenous; Intravesical	10 mg
Injection, powder, lyophilized, for solution	Intravenous; Intravesical	50 mg
Powder	Parenteral	10 MG
Injection, solution, concentrate	Intravenous; Intravesical	2 mg/ml
Injection, powder, for solution	Intravesical
Powder	Intravesical
Solution	Intravenous	10.000 mg
Suspension	Intravenous	2.00 mg
Injection, solution, concentrate	Intravenous; Parenteral	2 MG/ML
Injection, powder, lyophilized, for solution	Parenteral	50 mg
Injection, solution, concentrate	Intravenous
Solution	Intravenous	10 mg
Solution	Intravenous	50 mg
Solution	Intravenous; Intravesical	200000 mg
Solution	Parenteral	2 mg
Injection, powder, lyophilized, for solution	Intravenous	8.333 mg
Injection, solution, concentrate	Parenteral	10 mg/5ml
Injection, solution, concentrate	Parenteral	50 mg/25ml
Injection, solution
Injection, solution, concentrate	Intra-arterial; Intravenous; Intravesical	2.00 mg
Solution	Parenteral	10.00 mg
Solution	Intravenous; Intravesical	2 mg
Injection, powder, for solution	Intravenous	10 mg
Injection, powder, for solution	Intravenous	50 mg
Solution	Intravenous	2 mg
Injectable, liposomal	Intravenous	2 mg / mL
Powder	Intravenous; Parenteral	50 MG
Injection, powder, for solution		10 mg/1vial
Injection; injection, powder, lyophilized, for solution		10 mg
Injection, powder, for solution		50 mg/1vial
Injection; injection, powder, lyophilized, for solution		50 mg
Injection	Parenteral	10 mg/5ml
Injection	Parenteral	50 mg/25ml
Injection, powder, lyophilized, for solution	Intravenous	100 mg/50mL
Injection, powder, lyophilized, for solution	Intravenous	50 mg/25mL
Injection
Suspension	Intravenous	2 mg
Injection, powder, for solution
Injection, suspension		2 mg/1ml
Solution	Parenteral	2.000 mg
Injection, solution		2 mg/1ml
Solution	Parenteral	50.000 mg
Solution	Parenteral	10.000 mg
Solution		2 mg/1ml
Powder		10 mg/1vial
Powder		50 mg/1vial
Suspension	Intravenous	2 mg/1ml

Prices

Unit description	Cost	Unit
Doxorubicin 50 mg vial	132.0USD	vial
Doxil 2 mg/ml vial	115.78USD	ml
Adriamycin 50 mg vial	64.8USD	vial
Doxorubicin 10 mg vial	44.4USD	vial
Adriamycin 20 mg vial	26.4USD	vial
Adriamycin 10 mg vial	13.2USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5013556	No	1991-05-07	2009-10-20
CA1338702	No	1998-11-12	2013-11-12
CA1335565	No	1995-05-16	2012-05-16

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	229-231 °C	PhysProp
water solubility	~10 mg/ml	L45250
logP	1.27	HANSCH,C ET AL. (1995)
Caco2 permeability	-6.8	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	1.18 mg/mL	ALOGPS
logP	1.41	ALOGPS
logP	0.54	Chemaxon
logS	-2.7	ALOGPS
pKa (Strongest Acidic)	8.01	Chemaxon
pKa (Strongest Basic)	10.03	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	12	Chemaxon
Hydrogen Donor Count	6	Chemaxon
Polar Surface Area	206.07 Å²	Chemaxon
Rotatable Bond Count	5	Chemaxon
Refractivity	134.59 m³·mol^-1	Chemaxon
Polarizability	54.62 Å³	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	0	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	-	0.8092
Blood Brain Barrier	-	0.9951
Caco-2 permeable	-	0.799
P-glycoprotein substrate	Substrate	0.7861
P-glycoprotein inhibitor I	Non-inhibitor	0.8782
P-glycoprotein inhibitor II	Non-inhibitor	0.8382
Renal organic cation transporter	Non-inhibitor	0.9053
CYP450 2C9 substrate	Non-substrate	0.8042
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.5888
CYP450 1A2 substrate	Non-inhibitor	0.9045
CYP450 2C9 inhibitor	Non-inhibitor	0.9209
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.831
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8911
Ames test	AMES toxic	0.9198
Carcinogenicity	Non-carcinogens	0.9534
Biodegradation	Not ready biodegradable	0.9672
Rat acute toxicity	2.6644 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9752
hERG inhibition (predictor II)	Non-inhibitor	0.7195

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0a4i-9100210000-2b807cbc2c92b3239ce2
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-006t-0109000000-ac65f689e3fa439adddc
MS/MS Spectrum - , positive	LC-MS/MS	splash10-006t-0109000000-ac65f689e3fa439adddc
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-056v-0205090000-a3af4fb66a78a4f9d0e6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000w-0009130000-ba265262c021bc27de16
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-002e-1508690000-7c8fae113882b86ccf1e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000t-0009110000-26f3bf456970c7bbd515
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-02cu-1530920000-add2a703b4181a58e17c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-029y-1329650000-6eac9f445f5c4ef373d2

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	246.9922172	predicted	DarkChem Lite v0.1.0
[M-H]-	233.6495172	predicted	DarkChem Lite v0.1.0
[M-H]-	217.38579	predicted	DeepCCS 1.0 (2019)
[M+H]+	247.9719172	predicted	DarkChem Lite v0.1.0
[M+H]+	234.0055172	predicted	DarkChem Lite v0.1.0
[M+H]+	219.21068	predicted	DeepCCS 1.0 (2019)
[M+Na]+	247.1927172	predicted	DarkChem Lite v0.1.0
[M+Na]+	234.1975172	predicted	DarkChem Lite v0.1.0
[M+Na]+	224.81648	predicted	DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1000	N/A	N/A	A29278

Details1. DNA topoisomerase 2-alpha

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Ubiquitin binding
Specific Function: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name: TOP2A
Uniprot ID: P11388
Uniprot Name: DNA topoisomerase 2-alpha
Molecular Weight: 174383.88 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Rody A, Karn T, Gatje R, Ahr A, Solbach C, Kourtis K, Munnes M, Loibl S, Kissler S, Ruckhaberle E, Holtrich U, von Minckwitz G, Kaufmann M: Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast. 2007 Feb;16(1):86-93. Epub 2006 Sep 28. [Article]
Koehn H, Magan N, Isaacs RJ, Stowell KM: Differential regulation of DNA repair protein Rad51 in human tumour cell lines exposed to doxorubicin. Anticancer Drugs. 2007 Apr;18(4):419-25. [Article]
Hayashi S, Hatashita M, Matsumoto H, Shioura H, Kitai R, Kano E: Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis and necrosis induction. Int J Mol Med. 2006 Nov;18(5):909-15. [Article]
Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9. Epub 2007 Jun 19. [Article]
Menendez JA, Vellon L, Lupu R: DNA topoisomerase IIalpha (TOP2A) inhibitors up-regulate fatty acid synthase gene expression in SK-Br3 breast cancer cells: in vitro evidence for a 'functional amplicon' involving FAS, Her-2/neu and TOP2A genes. Int J Mol Med. 2006 Dec;18(6):1081-7. [Article]
Khalil OM, Gedawy EM, El-Malah AA, Adly ME: Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg Chem. 2019 Mar;83:262-276. doi: 10.1016/j.bioorg.2018.10.058. Epub 2018 Oct 30. [Article]

Details2. DNA

Kind

Nucleotide

Organism

Humans

Pharmacological action

Yes

Actions

Intercalation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

References

Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA: Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol Pharmacol. 1994 Apr;45(4):649-56. [Article]
Momparler RL, Karon M, Siegel SE, Avila F: Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res. 1976 Aug;36(8):2891-5. [Article]
Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH: Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. Biochemistry. 1990 Mar 13;29(10):2538-49. [Article]

Details3. Nucleolar and coiled-body phosphoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Poly(a) rna binding
Specific Function: Related to nucleologenesis, may play a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus. It has intrinsic GTPase and ATPas...
Gene Name: NOLC1
Uniprot ID: Q14978
Uniprot Name: Nucleolar and coiled-body phosphoprotein 1
Molecular Weight: 73602.49 Da

References

Kim YK, Lee WK, Jin Y, Lee KJ, Jeon H, Yu YG: Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140. J Biochem Mol Biol. 2006 Nov 30;39(6):774-81. [Article]

Details4. DNA topoisomerase 1

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Poly(a) rna binding
Specific Function: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name: TOP1
Uniprot ID: P11387
Uniprot Name: DNA topoisomerase 1
Molecular Weight: 90725.19 Da

References

Khalil OM, Gedawy EM, El-Malah AA, Adly ME: Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg Chem. 2019 Mar;83:262-276. doi: 10.1016/j.bioorg.2018.10.058. Epub 2018 Oct 30. [Article]

Details5. DNA topoisomerase 2-beta

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Protein kinase c binding
Specific Function: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name: TOP2B
Uniprot ID: Q02880
Uniprot Name: DNA topoisomerase 2-beta
Molecular Weight: 183265.825 Da

References

Khalil OM, Gedawy EM, El-Malah AA, Adly ME: Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg Chem. 2019 Mar;83:262-276. doi: 10.1016/j.bioorg.2018.10.058. Epub 2018 Oct 30. [Article]

Enzymes

Details1. Alcohol dehydrogenase [NADP(+)]

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: L-glucuronate reductase activity
Specific Function: Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyd...
Gene Name: AKR1A1
Uniprot ID: P14550
Uniprot Name: Alcohol dehydrogenase [NADP(+)]
Molecular Weight: 36572.71 Da

References

Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]

Details2. Aldose reductase

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Glyceraldehyde oxidoreductase activity
Specific Function: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name: AKR1B1
Uniprot ID: P15121
Uniprot Name: Aldose reductase
Molecular Weight: 35853.125 Da

Details3. Aldo-keto reductase family 1 member C3

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function: Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2....
Gene Name: AKR1C3
Uniprot ID: P42330
Uniprot Name: Aldo-keto reductase family 1 member C3
Molecular Weight: 36852.89 Da

References

Novotna R, Wsol V, Xiong G, Maser E: Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6. doi: 10.1016/j.toxlet.2008.06.858. Epub 2008 Jun 21. [Article]

Details4. Aldo-keto reductase family 1 member C4

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Retinal dehydrogenase activity
Specific Function: Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid...
Gene Name: AKR1C4
Uniprot ID: P17516
Uniprot Name: Aldo-keto reductase family 1 member C4
Molecular Weight: 37066.52 Da

References

Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]

Details5. Aldo-keto reductase family 1 member B10

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Retinal dehydrogenase activity
Specific Function: Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldeh...
Gene Name: AKR1B10
Uniprot ID: O60218
Uniprot Name: Aldo-keto reductase family 1 member B10
Molecular Weight: 36019.295 Da

References

Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]

Details6. Carbonyl reductase [NADPH] 1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Prostaglandin-e2 9-reductase activity
Specific Function: NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. ...
Gene Name: CBR1
Uniprot ID: P16152
Uniprot Name: Carbonyl reductase [NADPH] 1
Molecular Weight: 30374.73 Da

References

Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]

Details7. Carbonyl reductase [NADPH] 3

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Nadph binding
Specific Function: Has low NADPH-dependent oxidoreductase activity towards 4-benzoylpyridine and menadione (in vitro).
Gene Name: CBR3
Uniprot ID: O75828
Uniprot Name: Carbonyl reductase [NADPH] 3
Molecular Weight: 30849.97 Da

References

Bains OS, Karkling MJ, Lubieniecka JM, Grigliatti TA, Reid RE, Riggs KW: Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. J Pharmacol Exp Ther. 2010 Mar;332(3):755-63. doi: 10.1124/jpet.109.160614. Epub 2009 Dec 9. [Article]

Details8. Cytochrome P450 1B1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inhibitor
Inducer
Curator comments: There are limited data in the literature supporting the inhibitory actions of this drug on CYP1B1. The majority of the data suggests that it is an inducer of CYP1B1.

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP1B1
Uniprot ID: Q16678
Uniprot Name: Cytochrome P450 1B1
Molecular Weight: 60845.33 Da

References

Zordoky BN, El-Kadi AO: Induction of several cytochrome P450 genes by doxorubicin in H9c2 cells. Vascul Pharmacol. 2008 Oct-Dec;49(4-6):166-72. doi: 10.1016/j.vph.2008.07.004. Epub 2008 Jul 25. [Article]
Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [Article]
Zordoky BN, Anwar-Mohamed A, Aboutabl ME, El-Kadi AO: Acute doxorubicin toxicity differentially alters cytochrome P450 expression and arachidonic acid metabolism in rat kidney and liver. Drug Metab Dispos. 2011 Aug;39(8):1440-50. doi: 10.1124/dmd.111.039123. Epub 2011 May 13. [Article]
Grant MK, Seelig DM, Sharkey LC, Zordoky BN: Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice. Biol Sex Differ. 2017 Jan 7;8:1. doi: 10.1186/s13293-016-0124-4. eCollection 2017. [Article]

Details9. Cytochrome P450 2B6

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2B6
Uniprot ID: P20813
Uniprot Name: Cytochrome P450 2B6
Molecular Weight: 56277.81 Da

References

Masek V, Anzenbacherova E, Etrych T, Strohalm J, Ulbrich K, Anzenbacher P: Interaction of N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates with human liver microsomal cytochromes P450: comparison with free doxorubicin. Drug Metab Dispos. 2011 Sep;39(9):1704-10. doi: 10.1124/dmd.110.037986. Epub 2011 Jun 3. [Article]
Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [Article]
Potential CYP2B6 Substrates, Inhibitors, Inudcers (https://ctep.cancer.gov/protocoldevelopment/docs/cyp2b6.doc) [File]

Details10. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Le Guellec C, Lacarelle B, Catalin J, Durand A: Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5. [Article]
Flockhart Table of Drug Interactions [Link]

Details11. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Lu H, Chen CS, Waxman DJ: Potentiation of methoxymorpholinyl doxorubicin antitumor activity by P450 3A4 gene transfer. Cancer Gene Ther. 2009 May;16(5):393-404. doi: 10.1038/cgt.2008.93. Epub 2008 Nov 14. [Article]
Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R: Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem Pharmacol. 1993 Feb 24;45(4):853-61. [Article]
Diaz Flaque MC, Cayrol MF, Sterle HA, Del Rosario Aschero M, Diaz Albuja JA, Isse B, Farias RN, Cerchietti L, Rosemblit C, Cremaschi GA: Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells. Oncotarget. 2019 Apr 30;10(32):3051-3065. doi: 10.18632/oncotarget.26890. eCollection 2019 Apr 30. [Article]

Details12. NADPH--cytochrome P450 reductase

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function: This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name: POR
Uniprot ID: P16435
Uniprot Name: NADPH--cytochrome P450 reductase
Molecular Weight: 76689.12 Da

References

Gutierrez PL, Gee MV, Bachur NR: Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75. [Article]

Details13. NAD(P)H dehydrogenase [quinone] 1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Superoxide dismutase activity
Specific Function: The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vit...
Gene Name: NQO1
Uniprot ID: P15559
Uniprot Name: NAD(P)H dehydrogenase [quinone] 1
Molecular Weight: 30867.405 Da

References

Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [Article]

Details14. NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Ubiquitin protein ligase binding
Specific Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name: NDUFS2
Uniprot ID: O75306
Uniprot Name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
Molecular Weight: 52545.26 Da

References

Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]

Details15. NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Nadh dehydrogenase activity
Specific Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name: NDUFS3
Uniprot ID: O75489
Uniprot Name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
Molecular Weight: 30241.245 Da

References

Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]

Details16. NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Quinone binding
Specific Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name: NDUFS7
Uniprot ID: O75251
Uniprot Name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
Molecular Weight: 23563.3 Da

References

Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]

Details17. Nitric oxide synthase, brain

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Tetrahydrobiopterin binding
Specific Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. P...
Gene Name: NOS1
Uniprot ID: P29475
Uniprot Name: Nitric oxide synthase, brain
Molecular Weight: 160969.095 Da

References

Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]

Details18. Nitric oxide synthase, endothelial

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Tetrahydrobiopterin binding
Specific Function: Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induce...
Gene Name: NOS3
Uniprot ID: P29474
Uniprot Name: Nitric oxide synthase, endothelial
Molecular Weight: 133287.62 Da

References

Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]

Details19. Nitric oxide synthase, inducible

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Tetrahydrobiopterin binding
Specific Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity ...
Gene Name: NOS2
Uniprot ID: P35228
Uniprot Name: Nitric oxide synthase, inducible
Molecular Weight: 131116.3 Da

References

Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]

Details20. Xanthine dehydrogenase/oxidase

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Xanthine oxidase activity
Specific Function: Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name: XDH
Uniprot ID: P47989
Uniprot Name: Xanthine dehydrogenase/oxidase
Molecular Weight: 146422.99 Da

References

Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [Article]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Kratz F, Mansour A, Soltau J, Warnecke A, Fichtner I, Unger C, Drevs J: Development of albumin-binding doxorubicin prodrugs that are cleaved by prostate-specific antigen. Arch Pharm (Weinheim). 2005 Oct;338(10):462-72. [Article]
Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F: Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem. 2007 May-Jun;18(3):702-16. Epub 2007 Mar 23. [Article]

Transporters

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Fardel O, Lecureur V, Daval S, Corlu A, Guillouzo A: Up-regulation of P-glycoprotein expression in rat liver cells by acute doxorubicin treatment. Eur J Biochem. 1997 May 15;246(1):186-92. [Article]
Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [Article]
Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [Article]
Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [Article]
Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. [Article]
Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [Article]
Kim S, Kim SS, Bang YJ, Kim SJ, Lee BJ: In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines. Peptides. 2003 Jul;24(7):945-53. [Article]
Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I: Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8472-6. [Article]
Kusunoki N, Takara K, Tanigawara Y, Yamauchi A, Ueda K, Komada F, Ku Y, Kuroda Y, Saitoh Y, Okumura K: Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein. Jpn J Cancer Res. 1998 Nov;89(11):1220-8. [Article]
Li YC, Fung KP, Kwok TT, Lee CY, Suen YK, Kong SK: Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells. Chemotherapy. 2004 Jun;50(2):55-62. [Article]
Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. doi: 10.1002/ijc.24885. [Article]
Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV: Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23. [Article]
Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. doi: 10.1007/s00280-009-0949-1. Epub 2009 Mar 3. [Article]
Woodahl EL, Crouthamel MH, Bui T, Shen DD, Ho RJ: MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. doi: 10.1007/s00280-008-0906-4. Epub 2009 Jan 4. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	50000	N/A	N/A	A15963

Details2. Multidrug resistance-associated protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Transporter activity
Specific Function: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name: ABCC1
Uniprot ID: P33527
Uniprot Name: Multidrug resistance-associated protein 1
Molecular Weight: 171589.5 Da

References

Loe DW, Almquist KC, Cole SP, Deeley RG: ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem. 1996 Apr 19;271(16):9683-9. [Article]
Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. [Article]
Tribull TE, Bruner RH, Bain LJ: The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol Lett. 2003 Apr 30;142(1-2):61-70. [Article]
Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. [Article]
Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. [Article]
Wong IL, Chan KF, Tsang KH, Lam CY, Zhao Y, Chan TH, Chow LM: Modulation of multidrug resistance protein 1 (MRP1/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives. J Med Chem. 2009 Sep 10;52(17):5311-22. doi: 10.1021/jm900194w. [Article]
Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. doi: 10.1007/s00280-009-0949-1. Epub 2009 Mar 3. [Article]
Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [Article]

Details3. Canalicular multispecific organic anion transporter 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Organic anion transmembrane transporter activity
Specific Function: May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name: ABCC3
Uniprot ID: O15438
Uniprot Name: Canalicular multispecific organic anion transporter 2
Molecular Weight: 169341.14 Da

References

Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [Article]

Details4. Multidrug resistance-associated protein 6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Transporter activity
Specific Function: Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4...
Gene Name: ABCC6
Uniprot ID: O95255
Uniprot Name: Multidrug resistance-associated protein 6
Molecular Weight: 164904.81 Da

References

Cai J, Daoud R, Alqawi O, Georges E, Pelletier J, Gros P: Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6). Biochemistry. 2002 Jun 25;41(25):8058-67. [Article]
Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. [Article]

Details5. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Xenobiotic-transporting atpase activity
Specific Function: High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name: ABCG2
Uniprot ID: Q9UNQ0
Uniprot Name: ATP-binding cassette sub-family G member 2
Molecular Weight: 72313.47 Da

References

Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. [Article]
Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [Article]
Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. [Article]
Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [Article]
An Y, Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1529-42. doi: 10.1517/17425250903228834. [Article]
Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [Article]
Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F, Chen ZS, Tong XZ, Fu LW: Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18. [Article]
Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [Article]

Details6. Solute carrier family 22 member 16

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Organic cation transmembrane transporter activity
Specific Function: High affinity carnitine transporter; the uptake is partially sodium-ion dependent. Thought to mediate the L-carnitine secretion mechanism from testis epididymal epithelium into the lumen which is i...
Gene Name: SLC22A16
Uniprot ID: Q86VW1
Uniprot Name: Solute carrier family 22 member 16
Molecular Weight: 64613.58 Da

References

Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV: Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23. [Article]

Details7. Multidrug resistance-associated protein 7

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Atpase activity, coupled to transmembrane movement of substances
Specific Function: ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name: ABCC10
Uniprot ID: Q5T3U5
Uniprot Name: Multidrug resistance-associated protein 7
Molecular Weight: 161627.375 Da

References

Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]

Details8. ATP-binding cassette sub-family B member 8, mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Transporter activity
Specific Function: Not Available
Gene Name: ABCB8
Uniprot ID: Q9NUT2
Uniprot Name: ATP-binding cassette sub-family B member 8, mitochondrial
Molecular Weight: 79988.17 Da

References

Elliott AM, Al-Hajj MA: ABCB8 mediates doxorubicin resistance in melanoma cells by protecting the mitochondrial genome. Mol Cancer Res. 2009 Jan;7(1):79-87. doi: 10.1158/1541-7786.MCR-08-0235. [Article]

Details9. Bile salt export pump

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Transporter activity
Specific Function: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [Article]

Details10. RalA-binding protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Transmembrane transporter activity
Specific Function: Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the ma...
Gene Name: RALBP1
Uniprot ID: Q15311
Uniprot Name: RalA-binding protein 1
Molecular Weight: 76062.86 Da

References

Singhal SS, Singhal J, Nair MP, Lacko AG, Awasthi YC, Awasthi S: Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25. [Article]

Details11. Canalicular multispecific organic anion transporter 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Organic anion transmembrane transporter activity
Specific Function: Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name: ABCC2
Uniprot ID: Q92887
Uniprot Name: Canalicular multispecific organic anion transporter 1
Molecular Weight: 174205.64 Da

References

Folmer Y, Schneider M, Blum HE, Hafkemeyer P: Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-ABCC2 antisense constructs. Cancer Gene Ther. 2007 Nov;14(11):875-84. Epub 2007 Aug 17. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54

Doxorubicin

Identification

Structure for Doxorubicin (DB00997)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

References

References

References

Enzymes

References

References

References

References

References

References

References

References

References

References

References

References

References

References

References

References

References

References

References

Carriers

References

Transporters

References

References

References

References

References

References

References

References

References

References

References