Identification
- Summary
Melphalan is an alkylating agent used to treat multiple myeloma, ovarian carcinoma, uveal melanoma with unresectable hepatic metastases, and for high-dose conditioning before hematopoietic stem cell transplant in patients.
- Brand Names
- Alkeran, Evomela, Hepzato
- Generic Name
- Melphalan
- DrugBank Accession Number
- DB01042
- Background
Melphalan is a nitrogen mustard or bischloroethylamine type alkylating agent.7 It was first synthesized in the early 1950s by substituting L-phenylalanine for the methyl group on nitrogen mustard.4,5 Melphalan is used in the treatment of multiple myeloma and ovarian carcinoma.7 It is also used for high-conditioning before hematopoietic stem cell transplant.8 It is also used to treat uveal melanoma with unresectable hepatic metastases.9
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Melphalan (DB01042)
- Weight
- Average: 305.2
Monoisotopic: 304.074533244 - Chemical Formula
- C13H18Cl2N2O2
- Synonyms
- 3-(p-(Bis(2-chloroethyl)amino)phenyl)-L-alanine
- 3-p-(Di(2-chloroethyl)amino)-phenyl-L-alanine
- 4-(Bis(2-chloroethyl)amino)-L-phenylalanine
- L-3-(p-(Bis(2-chloroethyl)amino)phenyl)alanine
- L-PAM
- L-Phenylalanine mustard
- L-Sarcolysine
- Melfalano
- Melphalan
- Melphalanum
- p-Bis(beta-chloroethyl)aminophenylalanine
- p-Di-(2-chloroethyl)amino-L-phenylalanine
- p-L-Sarcolysin
- p-N-Bis(2-chloroethyl)amino-L-phenylalanine
- p-N,N-bis(2-chloroethyl)amino-L-phenylalanine
- Phenylalanine mustard
- Phenylalanine nitrogen mustard
- External IDs
- CB 3025
- CB-3025
- NCI-C04853
- NSC-241286
- NSC-8806
- SK 15673
- SK-15673
Pharmacology
- Indication
Melphalan is indicated for use as a high-dose conditioning treatment prior to hematopoietic stem cell transplantation in patients with multiple myeloma.8 It is also indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.7
Melphalan is a component of HEPZATO KIT, a liver-directed therapy indicated for the treatment of adults with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.9
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Multiple myeloma (mm) •••••••••••• •••••• Treatment of Unresectable hepatic metastases •••••••••••• ••••• •••••••• •• ••••••••• •• •••••••••• ••••• •••••••• Treatment of Unresectable ovarian cancer (epithelial) •••••••••••• •••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Melphalan possesses cytotoxic, immunosuppressive, and myeloablative activities.4,7 Melphalan produces chromosomal aberrations in vitro and in vivo; thus, it is considered to be potentially leukemogenic in humans. It also causes dose-limiting bone marrow suppression. The peak mean heart rate increased by 20 bpm from baseline following melphalan 100 mg/m2 for two consecutive days in multiple myeloma patients undergoing autologous stem cell transplantation.8
- Mechanism of action
Melphalan is an alkylating agent of the bischloroethylamine type.8 It is believed to be taken up by tumour cells via a neutral amino acid active pathway shared by leucine.5 Melphalan binds at the N7 position of guanine and induces inter-strand cross-links in DNA, disrupting DNA synthesis or transcription. It can also cause DNA-protein cross-linking and induce lesions in RNA, proteins, and lipids.1,2,3,5,6,8 Melphalan is cytotoxic in resting and rapidly dividing tumour cells.8
Target Actions Organism ADNA cross-linking/alkylationHumans - Absorption
The absorption of oral melphalan is highly variable concerning both the time to the first appearance of the drug in plasma (range: 0 to 6 hours) and peak plasma concentration (Cmax). The average absolute bioavailability of melphalan ranges from 56% to 93%. High variability in bioavailability may be due to incomplete intestinal absorption, variable first-pass hepatic metabolism, or rapid hydrolysis. Tmax was one hour in patients who received single oral doses of 0.2 mg/kg to 0.25 mg/kg of melphalan. Oral administration of melphalan with a high-fat meal may reduce melphalan exposure (AUC) by 36% to 54%.7
Mean (± SD) Cmax and AUC0-inf were 5.8 ± 1.5 mcg/mL and 451 ± 109 mcg x min/mL, respectively, following intravenous administration of 100 mg/m2 in multiple myeloma patients.8
- Volume of distribution
The volume of distribution of melphalan ranges from approximately 35.5 to 185.7 L/m2.8 Penetration into cerebrospinal fluid is low.7
- Protein binding
Protein binding of melphalan ranges from 50% to 90%. Serum albumin is the major binding protein, accounting for approximately 40% to 60% of the plasma protein binding, while α1-acid glycoprotein accounts for about 20% of the plasma protein binding. Approximately 30% of melphalan is covalently and irreversibly bound to plasma proteins.7,8
- Metabolism
Melphalan primarily undergoes chemical hydrolysis to inactive metabolites, monohydroxymelphalan and dihydroxymelphalan.7,8 No other melphalan metabolites have been observed in humans.7
Hover over products below to view reaction partners
- Route of elimination
About 5.8% to 21.3% of melphalan is excreted in urine.8
- Half-life
In patients given a single oral dose of 0.6 mg/kg of melphalan, the terminal elimination plasma half-life (± SD) was 1.5 ± 0.83 hours.7 Following intravenous administration, the terminal elimination half-life is approximately 75 minutes.8
- Clearance
Average total body clearance (CL) ranges from approximately 250 to 325 mL/min/m2.8
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The oral and intraperitoneal LD50 in rats is 4484 µg/kg and 11200 µg/kg, respectively. The subcutaneous LD50 in mice is 32 mg/kg.10
Overdoses resulting in death have been reported with melphalan. Overdoses, including intravenous doses up to 290 mg/m2 and oral doses up to 50 mg/day for 16 days, have been reported. Symptoms of overdose include severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, cholinomimetic effects, mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract. Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia, caused by an associated inappropriate secretion of ADH syndrome, has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely. The principal toxic effect is bone marrow suppression. Melphalan is not removed from plasma via hemodialysis, and overdose is typically managed by general supportive measures, with appropriate blood transfusions and antibiotics.7,8
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
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 softwareAbatacept The risk or severity of adverse effects can be increased when Melphalan is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Melphalan. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Melphalan. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Melphalan. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Melphalan. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Melphalan hydrochloride 1VXP4V453T 3223-07-2 OUUYBRCCFUEMLH-YDALLXLXSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alkeran Tablet 2 mg Oral Aspen Pharmacare Canada Inc. 1964-12-31 Not applicable Canada 
Alkeran Injection, powder, for solution; Kit 50 mg/10mL Intravenous ApoPharma USA, Inc. 2011-01-01 Not applicable US 
Alkeran Tablet, film coated 2 mg/1 Oral Physicians Total Care, Inc. 2005-08-15 2012-06-30 US Alkeran Kit 50 mg/10mL Intravenous Glaxosmithkline Inc 1993-03-16 2012-05-31 US Alkeran Tablet, film coated 2 mg/1 Oral Glaxosmithkline Inc 1984-05-10 2012-04-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Melphalan 50 mg/50mg Intravenous Bpi Labs Llc 2020-09-30 Not applicable US Melphalan Tablet 2 mg/1 Oral Alvogen Inc. 2017-03-22 Not applicable US Melphalan Injection, powder, for solution; Kit 50 mg/10mL Intravenous Fresenius Kabi USA, LLC 2017-12-22 Not applicable US Melphalan Hydrochloride Kit 50 mg/10mL Intravenous Sagent Pharmaceuticals 2017-03-15 2020-04-30 US Melphalan Hydrochloride Kit 50 mg/10mL Intravenous Athenex Pharmaceutical Division, Llc. 2019-07-30 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Alkeran Melphalan (50 mg) Kit; Powder, for solution; Solution Intra-arterial; Intravenous Aspen Pharmacare Canada Inc. 1995-12-31 Not applicable Canada Hepzato Kit Melphalan hydrochloride (50 mg/10mL) + Sodium chloride (0.9 mg/100mL) Kit Intra-arterial Delcath Systems, Inc. 2023-12-04 Not applicable US Melphalan for Injection Melphalan (50 mg) Kit; Powder, for solution; Solution Intravenous Apotex Corporation 2018-11-20 Not applicable Canada Melphalan for Injection Melphalan (50 mg) Kit; Powder, for solution; Solution Intra-arterial; Intravenous Marcan Pharmaceuticals Inc 2018-06-18 Not applicable Canada Taro-melphalan Melphalan (50 mg) Kit; Powder, for solution Intra-arterial; Intravenous Taro Pharmaceuticals, Inc. 2021-01-25 Not applicable Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ALKERAN 2 MG TABLET, 25 ADET Melphalan (2 mg) Tablet Oral VLD DANIŞMANLIK TIBBİ ÜRÜNLER VE TANITIM HİZMETLERİ LTD. ŞTİ. 2018-05-22 Not applicable Turkey 
Categories
- ATC Codes
- L01AA03 — Melphalan
- Drug Categories
- Alkylating Activity
- Alkylating Drugs
- Amino Acids
- Amino Acids, Aromatic
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Antineoplastic and Immunomodulating Agents
- Hydrocarbons, Halogenated
- Immunologic Factors
- Immunosuppressive Agents
- Mustard Compounds
- Myeloablative Agonists
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Nitrogen Mustard Analogues
- Nitrogen Mustard Compounds
- Noxae
- Toxic Actions
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Phenylalanine and derivatives
- Alternative Parents
- Phenylpropanoic acids / Amphetamines and derivatives / L-alpha-amino acids / Aniline and substituted anilines / Dialkylarylamines / Nitrogen mustard compounds / Aralkylamines / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids show 7 more
- Substituents
- 3-phenylpropanoic-acid / Alkyl chloride / Alkyl halide / Alpha-amino acid / Amine / Amino acid / Amphetamine or derivatives / Aniline or substituted anilines / Aralkylamine / Aromatic homomonocyclic compound show 22 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- organochlorine compound, non-proteinogenic L-alpha-amino acid, L-phenylalanine derivative, nitrogen mustard (CHEBI:28876)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q41OR9510P
- CAS number
- 148-82-3
- InChI Key
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N
- InChI
- InChI=1S/C13H18Cl2N2O2/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19/h1-4,12H,5-9,16H2,(H,18,19)/t12-/m0/s1
- IUPAC Name
- (2S)-2-amino-3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid
- SMILES
- N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O
References
- Synthesis Reference
- US3032584
- General References
- Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N: Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr;21(4):787-95. doi: 10.1021/tx7004508. Epub 2008 Feb 14. [Article]
- Povirk LF, Shuker DE: DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res. 1994 Dec;318(3):205-26. doi: 10.1016/0165-1110(94)90015-9. [Article]
- Lawley PD, Phillips DH: DNA adducts from chemotherapeutic agents. Mutat Res. 1996 Aug 17;355(1-2):13-40. doi: 10.1016/0027-5107(96)00020-6. [Article]
- Bayraktar UD, Bashir Q, Qazilbash M, Champlin RE, Ciurea SO: Fifty years of melphalan use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013 Mar;19(3):344-56. doi: 10.1016/j.bbmt.2012.08.011. Epub 2012 Aug 24. [Article]
- Kuczma M, Ding ZC, Zhou G: Immunostimulatory Effects of Melphalan and Usefulness in Adoptive Cell Therapy with Antitumor CD4+ T Cells. Crit Rev Immunol. 2016;36(2):179-191. doi: 10.1615/CritRevImmunol.2016017507. [Article]
- Poczta A, Rogalska A, Marczak A: Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies-Current Research and Clinical Approaches. J Clin Med. 2021 Apr 23;10(9):1841. doi: 10.3390/jcm10091841. [Article]
- DailyMed: Melphalan USP tablets for oral use [Link]
- FDA Approved Drug Products: EVOMELA (melphalan) for injection, for intravenous use (April 2022) [Link]
- FDA Approved Drug Products: HEPZATO (melphalan) KIT Hepatic Delivery System (HDS) for intra-arterial use [Link]
- Cayman Chemical: Melphalan MSDS [Link]
- External Links
- Human Metabolome Database
- HMDB0015176
- KEGG Drug
- D00369
- KEGG Compound
- C07122
- PubChem Compound
- 460612
- PubChem Substance
- 46509130
- ChemSpider
- 405297
- BindingDB
- 50025837
- 6718
- ChEBI
- 28876
- ChEMBL
- CHEMBL852
- ZINC
- ZINC000000001673
- Therapeutic Targets Database
- DAP000791
- PharmGKB
- PA450354
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Melphalan
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 Completed Treatment Multiple Myeloma (MM) 1 4 Recruiting Treatment B-Cell Non-Hodgkin Lymphoma (NHL) / Burkitt Lymphoma / Diffuse Large B-Cell Lymphoma (DLBCL) / Primary Central Nervous System Lymphoma / Primary Mediastinal Lymphoma 1 4 Recruiting Treatment Multiple Myeloma (MM) 1 4 Terminated Treatment Multiple Myeloma (MM) 1 3 Active Not Recruiting Treatment Ganglioneuroblastoma / Neuroblastoma (NB) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Antibioticos Ltd.
- Bioniche Pharma
- Cardinal Health
- Catalent Pharma Solutions
- Generamedix Inc.
- GlaxoSmithKline Inc.
- Nerviano Medical Science S.R.L.
- Oso Biopharmaceuticals Manufacturing LLC
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Injection, powder, for solution Parenteral 50 MG/10ML Injection, powder, for solution; kit Intravenous 50 mg/10mL Kit; powder, for solution; solution Intra-arterial; Intravenous Tablet Oral 2 mg Tablet Oral 2 mg/1 Tablet Oral 5 MG Tablet, film coated Oral 2 mg/1 Tablet, film coated Oral 2 MG Tablet; tablet, film coated Oral 2 MG Tablet, film coated Oral Injection Intravenous 50 mg Injection, powder, lyophilized, for solution Intravenous Tablet, film coated Oral 2.00 mg Tablet Oral Tablet, film coated Oral 200000 mg Injection, powder, lyophilized, for solution Parenteral 50 mg Injection, powder, lyophilized, for solution Parenteral 5000000 mg Injection, powder, lyophilized, for solution Intravenous 50 mg/10mL Kit Intra-arterial Injection, powder, for solution 50 MG Injection, powder, for solution Intravenous Injection, powder, for solution Parenteral 50 mg Kit; powder, for solution Intravenous 50 mg / vial Kit; powder, for solution; solution Intravenous Kit Intravenous 50 mg/10mL Kit Intravenous 50 mg/15mL Solution Parenteral 50 mg Injection, powder, for solution Parenteral Injection, powder, lyophilized, for solution Intravenous 50 mg Injection, powder, for solution Intravenous 200 mg Injection, powder, for solution Intravenous 50 mg Powder Intravenous 200 MG Powder Intravenous 50 MG Kit; powder, for solution Intra-arterial; Intravenous Powder Intravenous 50 mg/1vial Tablet, coated Oral 2 mg - Prices
Unit description Cost Unit Alkeran 50 mg vial 1971.72USD vial Melphalan hcl 50 mg vial 1845.6USD vial Alkeran 2 mg tablet 5.65USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA1341114 No 2000-10-10 2017-10-10 Canada US8410077 No 2013-04-02 2029-03-13 US US9200088 No 2015-12-01 2029-03-13 US US9493582 No 2016-11-15 2033-02-27 US US10040872 No 2018-08-07 2034-01-30 US US10864183 No 2020-12-15 2030-05-28 US US10940128 No 2021-03-09 2030-06-14 US US11020363 No 2021-06-01 2030-05-28 US US11633528 No 2012-11-07 2032-11-07 US US10369264 No 2019-08-06 2032-11-07 US US10098997 No 2018-10-16 2032-11-07 US US11083831 No 2021-08-10 2032-12-30 US US10537520 No 2020-01-21 2036-06-29 US US10195334 No 2019-02-05 2033-01-16 US US11241522 No 2012-11-07 2032-11-07 US US9314561 No 2016-04-19 2034-02-07 US US9707331 No 2017-07-18 2034-09-17 US US10569004 No 2020-02-25 2032-11-07 US US11833286 No 2012-12-30 2032-12-30 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 180 https://www.fishersci.com/store/msds?partNumber=AC458650010&productDescription=MELPHALAN%2C+94%25+1GR&vendorId=VN00032119&countryCode=US&language=en - Predicted Properties
Property Value Source logP 0.25 Chemaxon pKa (Strongest Acidic) 1.29 Chemaxon pKa (Strongest Basic) 9.51 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 66.56 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 78.23 m3·mol-1 Chemaxon Polarizability 31.38 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9523 Blood Brain Barrier - 0.6073 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.5 P-glycoprotein inhibitor I Non-inhibitor 0.983 P-glycoprotein inhibitor II Non-inhibitor 0.9192 Renal organic cation transporter Non-inhibitor 0.811 CYP450 2C9 substrate Non-substrate 0.8457 CYP450 2D6 substrate Non-substrate 0.7432 CYP450 3A4 substrate Non-substrate 0.7553 CYP450 1A2 substrate Inhibitor 0.779 CYP450 2C9 inhibitor Non-inhibitor 0.9348 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9193 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9863 Ames test AMES toxic 0.9108 Carcinogenicity Non-carcinogens 0.7873 Biodegradation Not ready biodegradable 0.9746 Rat acute toxicity 3.9179 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8187 hERG inhibition (predictor II) Non-inhibitor 0.8488
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 172.3496644 predictedDarkChem Lite v0.1.0 [M-H]- 166.4261 predictedDeepCCS 1.0 (2019) [M+H]+ 172.9870644 predictedDarkChem Lite v0.1.0 [M+H]+ 168.7841 predictedDeepCCS 1.0 (2019) [M+Na]+ 172.5926644 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.87724 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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Yes
Cross-linking/alkylation
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Monahan SD, Subbotin VM, Budker VG, Slattum PM, Neal ZC, Herweijer H, Wolff JA: Rapidly reversible hydrophobization: an approach to high first-pass drug extraction. Chem Biol. 2007 Sep;14(9):1065-77. [Article]
- Lee PC, Kakadiya R, Su TL, Lee TC: Combination of bifunctional alkylating agent and arsenic trioxide synergistically suppresses the growth of drug-resistant tumor cells. Neoplasia. 2010 May;12(5):376-87. [Article]
- Wang F, Li F, Ganguly M, Marky LA, Gold B, Egli M, Stone MP: A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards. Biochemistry. 2008 Jul 8;47(27):7147-57. doi: 10.1021/bi800375m. Epub 2008 Jun 13. [Article]
- Vasquez KM: Targeting and processing of site-specific DNA interstrand crosslinks. Environ Mol Mutagen. 2010 Jul;51(6):527-39. doi: 10.1002/em.20557. [Article]
- Dimopoulos MA, Souliotis VL, Anagnostopoulos A, Bamia C, Pouli A, Baltadakis I, Terpos E, Kyrtopoulos SA, Sfikakis PP: Melphalan-induced DNA damage in vitro as a predictor for clinical outcome in multiple myeloma. Haematologica. 2007 Nov;92(11):1505-12. [Article]
- Chen Q, Van der Sluis PC, Boulware D, Hazlehurst LA, Dalton WS: The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells. Blood. 2005 Jul 15;106(2):698-705. Epub 2005 Mar 31. [Article]
- Souliotis VL, Dimopoulos MA, Episkopou HG, Kyrtopoulos SA, Sfikakis PP: Preferential in vivo DNA repair of melphalan-induced damage in human genes is greatly affected by the local chromatin structure. DNA Repair (Amst). 2006 Aug 13;5(8):972-85. Epub 2006 Jun 15. [Article]
- Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N: Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr;21(4):787-95. doi: 10.1021/tx7004508. Epub 2008 Feb 14. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- 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
- FDA Approved Drug Products: EVOMELA (melphalan) for injection, for intravenous use (April 2022) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- FDA Approved Drug Products: EVOMELA (melphalan) for injection, for intravenous use (April 2022) [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Toxin transporter activity
- Specific Function
- Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
- Gene Name
- SLC22A3
- Uniprot ID
- O75751
- Uniprot Name
- Solute carrier family 22 member 3
- Molecular Weight
- 61279.485 Da
References
- Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y: Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009 Feb 15;69(4):1494-501. doi: 10.1158/0008-5472.CAN-08-2483. Epub 2009 Feb 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Peptide antigen binding
- Specific Function
- Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular a...
- Gene Name
- SLC7A5
- Uniprot ID
- Q01650
- Uniprot Name
- Large neutral amino acids transporter small subunit 1
- Molecular Weight
- 55009.62 Da
References
- Moscow JA, Swanson CA, Cowan KH: Decreased melphalan accumulation in a human breast cancer cell line selected for resistance to melphalan. Br J Cancer. 1993 Oct;68(4):732-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Neutral amino acid transmembrane transporter activity
- Specific Function
- Sodium-independent, high affinity transport of small neutral D- and L-amino acids. May play a role in the modulation of glutamatergic transmission through mobilization of D-serine at the glutamater...
- Gene Name
- SLC7A10
- Uniprot ID
- Q9NS82
- Uniprot Name
- Asc-type amino acid transporter 1
- Molecular Weight
- 56797.4 Da
References
- Moscow JA, Swanson CA, Cowan KH: Decreased melphalan accumulation in a human breast cancer cell line selected for resistance to melphalan. Br J Cancer. 1993 Oct;68(4):732-7. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54