NAV

Trastuzumab deruxtecan

Identification

Summary

Trastuzumab deruxtecan is an antibody used to treat certain types of unresectable or metastatic HER2 positive breast cancer.

Brand Names
Enhertu
Generic Name
Trastuzumab deruxtecan
DrugBank Accession Number
DB14962
Background

Trastuzumab deruxtecan is a HER2-directed antibody attached to a topoisomerase inhibitor that is approved for use in certain types of treatment-resistant HER2-positive cancers.6 It is classified as an antibody-drug conjugate. The cleavable peptide linker used to bind the antibody and drug in this product distinguishes it from other members of its class.4

Trastuzumab deruxtecan was developed by Daiichi Sankyo in collaboration with AstraZeneca and was first approved by the FDA in 2019.6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • fam-trastuzumab deruxtecan-nxki
  • Trastuzumab deruxtecan
External IDs
  • DS-8201
  • DS-8201A
  • WHO 10516
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Pharmacology

Indication

In the US, trastuzumab deruxtecan is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.6 It is also indicated to treat adults with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.6 Trastuzumab deruxtecan is also indicated to treat adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.6

In Canada, trastuzumab deruxtecan is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have previously been treated with trastuzumab emtansine, or who have received at least one prior anti-HER2-based regimen either in the metastatic setting or in the adjuvant/neoadjuvant setting who have experienced disease recurrence during or within 6 months of adjuvant/neoadjuvant therapy.8 Trastuzumab deruxtecan is also indicated in Canada for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received at least one prior line of chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.8

In Europe, trastuzumab deruxtecan is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens and unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.9 It is also indicated for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.9 It is also indicated as a monotherapy for the treatment of adult patients with advanced non-small cell lung cancer whose tumors have an activating HER2 mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy.9

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAdvanced gastric adenocarcinoma••••••••••••••••••••••••••• ••••••• •••• ••••••••••••••••••••• ••••••• •••••••••••• ••• ••••••••
Treatment ofAdvanced gastroesophageal adenocarcinoma••••••••••••••••••••••••••• ••••••• •••• ••••••••••••••••••••• ••••••• •••••••••••• ••• ••••••••
Treatment ofAdvanced non-small cell lung cancer (nsclc)••••••••••••••••••••••••••• ••••••• •••••••••••• ••• ••••••••
Treatment ofMetastatic breast cancer••••••••••••••••••••••••••• ••••••• •••••••••••• ••• ••••••••
Treatment ofUnresectable breast cancer••••••••••••••••••••••••••• ••••••• •••••••••••• ••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Trastuzumab demonstrates antitumor activity against certain types of HER2 positive breast cancer, however, clinical trials are still ongoing to confirm its efficacy.3,6,7 By exploiting both targeted antibody and cytotoxic effects, trastuzumab deruxtecan can effectively destroy tumors.4

The FDA label warns of a potential risk for neutropenia, interstitial lung disease/pneumonitis, and left ventricular dysfunction following the use of this drug.6

Mechanism of action

Trastuzumab deruxtecan is a humanized anti-HER2 IgG1 antibody, targeting cancer cause by mutation of the HER2 gene. In addition, the small molecule portion of this drug, deruxtecan (DXd), is a topoisomerase I inhibitor.1,6 It is attached to the antibody by a peptide linker. After trastuzumab deruxtecan binds to HER2 found on malignant cells, it is internalized and linker cleavage occurs through the actions of lysosomal enzymes. After it is released through cleavage, DXd causes targeted DNA damage and apoptosis in cancer cells, due to the ability to cross cell membranes.4,6

Normally, drugs in this class (antibody-drug conjugates) present a challenge. The monoclonal antibody accurately targets cancer cells, however exert limited killing action. The addition of a cytotoxic agent (a topoisomerase I inhibitor in this case) effectively kills dividing cancer cells, including those in the healthy tissues, leading to various adverse effects. The peptide linker used to formulate this drug is cleavable, which is unique to other antibody-drug conjugates, allowing for increased efficacy and reduced drug resistance to topoisomerase.4

TargetActionsOrganism
AHigh affinity immunoglobulin gamma Fc receptor I
antibody
Humans
ADNA topoisomerase 1
inhibitor
Humans
Absorption

The Cmax of trastuzumab deruxtecan at normal therapeutic doses was 122 μg/mL (20%). The AUC of trastuzumab deruxtecan was 735 μg·day/mL (31%).6

Volume of distribution

The estimated volume of distribution of trastuzumab deruxtecan in the central compartment is 2.77 L, according to a population based pharmacokinetic study.6 Pharmacokinetic studies found that the unchanged drug is distributed in the blood and is not significantly retained in tissues.2

Protein binding

The Dxd portion of the drug has a plasma protein binding estimated at 97%.6

Metabolism

Trastuzumab deruxtecan is likely broken down into small peptides and amino acids through catabolism, just as the metabolism of endogenous IgG.5,6 Cathepsin B and L enzymes are thought to be involved in the cleavage of the peptide linker that joins the topoisomerase I inhibitor and the antibody.4 In vitro, DXd, the topoisomerase inhibitor portion of the drug, is found to be metabolized by CYP3A4.6

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Route of elimination

A pharmacokinetic study revealed that this drug was mainly excreted in the feces. Another study determined that 67% of a dose was excreted in the feces.2,4 Unmetabolized DXd was found in the urine during a pharmacokinetic study.2

Half-life

In a pharmacokinetic study, the median elimination half-life of trastuzumab deruxtecan was about 5.8 days.6

Clearance

Trastuzumab deruxtecan is rapidly cleared from systemic circulation.2 Estimated systemic clearance of trastuzumab deruxtecan is 0.42 L/day, according to a population pharmacokinetic analysis. DXd showed a systemic clearance of about 19.2 L/h.6

Adverse Effects
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Toxicity

LD50 and overdose information are not currently available, but effects of an overdose are likely to impact the lungs, heart, and circulatory system, leading to significant toxicity.6

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.
DrugInteraction
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interactions in your software
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Trastuzumab deruxtecan.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Trastuzumab deruxtecan.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Trastuzumab deruxtecan.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Trastuzumab deruxtecan.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Trastuzumab deruxtecan.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnhertuPowder, for solution100 mg / vialIntravenousAstra Zeneca2021-07-09Not applicableCanada flag
EnhertuInjection, powder, lyophilized, for solution100 mg/5mLIntravenousDaiichi Sankyo Inc.2019-12-20Not applicableUS flag
EnhertuInjection, powder, for solution100 mgIntravenousDaiichi Sankyo Europe, Gmb H2021-03-03Not applicableEU flag

Categories

ATC Codes
L01FD04 — Trastuzumab deruxtecan
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
5384HK7574
CAS number
1826843-81-5

References

Synthesis Reference

Nakada T, Masuda T, Naito H, Yoshida M, Ashida S, Morita K, Miyazaki H, Kasuya Y, Ogitani Y, Yamaguchi J, Abe Y2, Honda T2. (2016).Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorg Med Chem Lett.,Mar 15;26(6):1542-1545

General References
  1. Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S: Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29. [Article]
  2. Nagai Y, Oitate M, Shiozawa H, Ando O: Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys. Xenobiotica. 2019 Sep;49(9):1086-1096. doi: 10.1080/00498254.2018.1531158. Epub 2019 Jan 4. [Article]
  3. Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I: Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2019 Dec 11. doi: 10.1056/NEJMoa1914510. [Article]
  4. Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L, Chen L, Zhu Y, Guo C, Shi J, Yu D: Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019 Dec 1;183:111682. doi: 10.1016/j.ejmech.2019.111682. Epub 2019 Sep 6. [Article]
  5. Kendrick F, Evans ND, Arnulf B, Avet-Loiseau H, Decaux O, Dejoie T, Fouquet G, Guidez S, Harel S, Hebraud B, Javaugue V, Richez V, Schraen S, Touzeau C, Moreau P, Leleu X, Harding S, Chappell MJ: Analysis of a Compartmental Model of Endogenous Immunoglobulin G Metabolism with Application to Multiple Myeloma. Front Physiol. 2017 Mar 17;8:149. doi: 10.3389/fphys.2017.00149. eCollection 2017. [Article]
  6. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
  7. FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies [Link]
  8. Health Canada Approved Drug Products: Enhertu (trastuzumab deruxtecan) powder for concentrate for intravenous infusion [Link]
  9. EMA Approved Drug Products: Enhertu (Trastuzumab deruxtecan) Powder for concentrate for solution for infusion. [Link]
RxNav
2267574
Wikipedia
Trastuzumab_deruxtecan
FDA label
Download (590 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingTreatmentBreast Cancer1
4RecruitingDiagnosticAnatomic Stage IV Breast Cancer AJCC v8 / Brain Metastases / Metastatic Breast Carcinoma1
3Active Not RecruitingTreatmentAdvanced or Metastatic Breast Cancer1
3Active Not RecruitingTreatmentBreast Cancer4
3Active Not RecruitingTreatmentHER2-Positive Primary Breast Cancer / Residual Invasive Breast Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous100 MG
Injection, powder, lyophilized, for solutionIntravenous100 mg/5mL
Powder, for solutionIntravenous100 mg / vial
SolutionIntravenous100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Details1. High affinity immunoglobulin gamma Fc receptor I
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Receptor signaling protein activity
Specific Function
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name
FCGR1A
Uniprot ID
P12314
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
Molecular Weight
42631.525 Da
References
  1. Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S: Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29. [Article]
  2. Nagai Y, Oitate M, Shiozawa H, Ando O: Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys. Xenobiotica. 2019 Sep;49(9):1086-1096. doi: 10.1080/00498254.2018.1531158. Epub 2019 Jan 4. [Article]
  3. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details2. 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
  1. Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S: Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29. [Article]
  2. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]

Enzymes

Details1. Lysosomal alpha-glucosidase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Lysosomal glucosidase is a popular lysosomal enzyme and likely participates in the breakdown of this drug, but other lysosomal enzymes also contribute.
General Function
Maltose alpha-glucosidase activity
Specific Function
Essential for the degradation of glygogen to glucose in lysosomes.
Gene Name
GAA
Uniprot ID
P10253
Uniprot Name
Lysosomal alpha-glucosidase
Molecular Weight
105322.935 Da
References
  1. Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L, Chen L, Zhu Y, Guo C, Shi J, Yu D: Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019 Dec 1;183:111682. doi: 10.1016/j.ejmech.2019.111682. Epub 2019 Sep 6. [Article]
  2. Wolska-Washer A, Robak T: Safety and Tolerability of Antibody-Drug Conjugates in Cancer. Drug Saf. 2019 Feb;42(2):295-314. doi: 10.1007/s40264-018-0775-7. [Article]
  3. Pernas S, Tolaney SM: HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol. 2019 Mar 19;11:1758835919833519. doi: 10.1177/1758835919833519. eCollection 2019. [Article]
  4. Rinnerthaler G, Gampenrieder SP, Greil R: HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. Int J Mol Sci. 2019 Mar 5;20(5). pii: ijms20051115. doi: 10.3390/ijms20051115. [Article]
Details2. DNA topoisomerase 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L, Chen L, Zhu Y, Guo C, Shi J, Yu D: Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019 Dec 1;183:111682. doi: 10.1016/j.ejmech.2019.111682. Epub 2019 Sep 6. [Article]
  2. Wolska-Washer A, Robak T: Safety and Tolerability of Antibody-Drug Conjugates in Cancer. Drug Saf. 2019 Feb;42(2):295-314. doi: 10.1007/s40264-018-0775-7. [Article]
  3. Pernas S, Tolaney SM: HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol. 2019 Mar 19;11:1758835919833519. doi: 10.1177/1758835919833519. eCollection 2019. [Article]
  4. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details3. Cathepsin B
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Proteoglycan binding
Specific Function
Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
Gene Name
CTSB
Uniprot ID
P07858
Uniprot Name
Cathepsin B
Molecular Weight
37821.35 Da
References
  1. Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L, Chen L, Zhu Y, Guo C, Shi J, Yu D: Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019 Dec 1;183:111682. doi: 10.1016/j.ejmech.2019.111682. Epub 2019 Sep 6. [Article]
  2. Rinnerthaler G, Gampenrieder SP, Greil R: HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. Int J Mol Sci. 2019 Mar 5;20(5). pii: ijms20051115. doi: 10.3390/ijms20051115. [Article]
Details4. Cathepsin L1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Serpin family protein binding
Specific Function
Important for the overall degradation of proteins in lysosomes.
Gene Name
CTSL
Uniprot ID
P07711
Uniprot Name
Cathepsin L1
Molecular Weight
37563.97 Da
References
  1. Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L, Chen L, Zhu Y, Guo C, Shi J, Yu D: Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019 Dec 1;183:111682. doi: 10.1016/j.ejmech.2019.111682. Epub 2019 Sep 6. [Article]
  2. Rinnerthaler G, Gampenrieder SP, Greil R: HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. Int J Mol Sci. 2019 Mar 5;20(5). pii: ijms20051115. doi: 10.3390/ijms20051115. [Article]
Details5. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
  1. Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L, Chen L, Zhu Y, Guo C, Shi J, Yu D: Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019 Dec 1;183:111682. doi: 10.1016/j.ejmech.2019.111682. Epub 2019 Sep 6. [Article]
  2. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]

Transporters

Details1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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
  1. Nagai Y, Oitate M, Shiozawa H, Ando O: Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys. Xenobiotica. 2019 Sep;49(9):1086-1096. doi: 10.1080/00498254.2018.1531158. Epub 2019 Jan 4. [Article]
  2. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details2. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details3. Solute carrier organic anion transporter family member 1B3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details4. Multidrug and toxin extrusion protein 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details5. Multidrug resistance-associated protein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
  1. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]
Details6. 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
  1. FDA Approved Drug Products: Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use [Link]

Drug created at May 20, 2019 14:38 / Updated at December 22, 2023 19:51