Explore a selection of our essential drug information below, or:
Identification
- Summary
Oxaliplatin is a platinum based chemotherapy agent used to treat carcinoma of the colon or rectum or stage III colon cancer.
- Generic Name
- Oxaliplatin
- DrugBank Accession Number
- DB00526
- Background
Oxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. Compared to cisplatin the two amine groups are replaced by diamino cyclohexane (DACH) group to provide a greater antitumor effect.2 However, this leads to poorer water solubility, which was compensated by the addition of the chloride moieties.2 Due to this chemical moiety, oxaliplatin readily undergoes non-enzymatic biotransformation, thus complicating oxaliplatin's pharmacokinetics.3 Like most platinum-based compounds, oxaliplatin's mechanism of action is primarily through DNA damage through DNA crosslinking, particularly intrastrand and interstrand crosslinking.3 However, due to the structure of oxaliplatin, its adducts make the binding of mismatch repair protein to DNA harder compared to cisplatin or carboplatin's adducts, resulting in greater cytotoxic effects.3 The DACH moiety also prevents cross-resistance with cisplatin and carboplatin.2
Although oxaliplatin has been investigated as a monotherapy, it is typically administered in combination with fluorouracil and leucovorin, known as the FOLFOX regimen, for the treatment of colorectal cancer.1,2 This is an effective combination treatment both as a first-line treatment and in patients refractory to an initial fluorouracil and leucovorin combination. Ongoing trials have also shown promising results for oxaliplatin use in nonHodgkin’s lymphoma, breast cancer, mesothelioma, and non-small cell lung cancer.2
Oxaliplatin was approved by the FDA on January 9, 2004 and is currently marketed by Sanofi-Aventis under the trademark Eloxatin®.7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Oxaliplatin (DB00526)
- Weight
- Average: 397.294
Monoisotopic: 397.060149 - Chemical Formula
- C8H14N2O4Pt
- Synonyms
- (SP-4-2-(1R-TRANS))-(1,2-CYCLOHEXANEDIAMINE-N,N')(ETHANEDIOATO(2-)-O,O')PLATINUM
- Diaminocyclohexane Oxalatoplatinum
- L-OHP
- Oxalatoplatin
- Oxalatoplatinum
- Oxaliplatin
- oxaliplatine
- oxaliplatino
- oxaliplatinum
- PLATINUM, ((1R,2R)-1,2-CYCLOHEXANEDIAMINE-.KAPPA.N,.KAPPA.N')(ETHANEDIOATO(2-)-.KAPPA.O1,.KAPPA.O2)-, (SP-4-2)-
- External IDs
- JM-83
- NSC-266046
- RP-54780
- SR-96669
Pharmacology
- Indication
Oxaliplatin, in combination with infusional fluorouracil and leucovorin, is indicated for the treatment of advanced colorectal cancer and adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.4
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 Used in combination to treat Advanced colorectal cancer Regimen in combination with: Fluorouracil (DB00544), Leucovorin (DB00650) •••••••••••• ••••••••• Used as adjunct in combination to treat Stage iii colon cancer Regimen in combination with: Leucovorin (DB00650), Fluorouracil (DB00544) •••••••••••• •••••••• ••••••••• •• ••• •••••••••• ••••• ••••••••• - 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
In vivo studies have shown antitumor activities of oxaliplatin against colon carcinoma. In combination with fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models (HT29 [colon], GR [mammary], and L1210 [leukemia]).4
- Mechanism of action
Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both inter and intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific.4
Target Actions Organism ADNA adductcross-linking/alkylationHumans - Absorption
The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. After a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m2, pharmacokinetic parameters expressed as ultrafiltrable platinum was Cmax of 0.814 mcg/mL. Interpatient and intrapatient variability in ultrafiltrable platinum exposure (AUC0-48hr) assessed over 3 cycles was 23% and 6%, respectively.4
- Volume of distribution
After a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m2, the volume of distribution is 440 L.At the end of a 2-hour infusion, approximately 15% of the administered platinum is present in the systemic circulation. The remaining 85% is rapidly distributed into tissues or eliminated in the urine.4
- Protein binding
In patients, plasma protein binding of platinum is irreversible and is greater than 90%. The main binding proteins are albumin and gamma-globulins.4
Platinum also binds irreversibly and accumulates (approximately 2-fold) in erythrocytes, where it appears to have no relevant activity. No platinum accumulation was observed in plasma ultrafiltrate following 85 mg/m2 every two weeks.4
- Metabolism
Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation. There is no evidence of cytochrome P450-mediated metabolism in vitro. Up to 17 platinum-containing derivatives have been observed in plasma ultrafiltrate samples from patients, including several cytotoxic species (monochloro DACH platinum, dichloro DACH platinum, and monoaquo and diaquo DACH platinum) and a number of noncytotoxic, conjugated species.4
Hover over products below to view reaction partners
- Route of elimination
The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of ELOXATIN, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%.4
- Half-life
The decline of ultrafilterable platinum levels following oxaliplatin administration is triphasic with two distribution phases: t1/2α; 0.43 hours and t1/2β; 16.8 hours. This is followed by a long terminal elimination phase that lasts 391 hours (t1/2γ).4
- Clearance
Platinum was cleared from plasma at a rate (10-17 L/h) that was similar to or exceeded the average human glomerular filtration rate (GFR; 7.5 L/h). The renal clearance of ultrafiltrable platinum is significantly correlated with GFR.4
- 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 maximum dose of oxaliplatin that has been administered in a single infusion is 825 mg. Several cases of overdoses have been reported with oxaliplatin. Adverse reactions observed following an overdosage were grade 4 thrombocytopenia (less than 25,000/mm3) without bleeding, anemia, sensory neuropathy (including paresthesia, dysesthesia, laryngospasm, and facial muscle spasms), gastrointestinal disorders (including nausea, vomiting, stomatitis, flatulence, abdomen enlarged and grade 4 intestinal obstruction), grade 4 dehydration, dyspnea, wheezing, chest pain, respiratory failure, severe bradycardia, and death. Closely monitor patients suspected of receiving an overdose, including for the adverse reactions described above, and administer appropriate supportive treatment.4
Based on its direct interaction with DNA, ELOXATIN can cause fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriages related to the use of oxaliplatin. Reproductive toxicity studies demonstrated adverse effects on embryo-fetal development in rats at maternal doses that were below the recommended human dose based on body surface area. Advise a pregnant woman of the potential risk to a fetus.4
In the adjuvant treatment trial, 400 patients who received oxaliplatin with fluorouracil/leucovorin were greater than or equal to 65 years. The effect of oxaliplatin in patients greater than or equal to 65 years was not conclusive. Patients greater than or equal to 65 years receiving ELOXATIN experienced more diarrhea and grade 3-4 neutropenia (45% vs 39%) compared to patients less than 65 years.4
The AUC of unbound platinum in plasma ultrafiltrate was increased in patients with renal impairment. No dose reduction is recommended for patients with mild (creatinine clearance 50 to 79 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal impairment, calculated by Cockcroft-Gault equation. Reduce the dose of oxaliplatin in patients with severe renal impairment (creatinine clearance less than 30 mL/min).4
Long-term animal studies have not been performed to evaluate the carcinogenic potential of oxaliplatin. Oxaliplatin was not mutagenic to bacteria (Ames test) but was mutagenic to mammalian cells in vitro (L5178Y mouse lymphoma assay). Oxaliplatin was clastogenic both in vitro (chromosome aberration in human lymphocytes) and in vivo (mouse bone marrow micronucleus assay).4
In a fertility study, male rats were given oxaliplatin at 0, 0.5, 1, or 2 mg/kg/day for five days every 21 days for a total of three cycles prior to mating with females that received two cycles of oxaliplatin on the same schedule. A dose of 2 mg/kg/day (less than one-seventh the recommended human dose on a body surface area basis) did not affect the pregnancy rate but resulted in 97% postimplantation loss (increased early resorptions, decreased live fetuses, decreased live births), and delayed growth (decreased fetal weight).4
Testicular damage, characterized by degeneration, hypoplasia, and atrophy, was observed in dogs administered oxaliplatin at 0.75 mg/kg/day (approximately one-sixth of the recommended human dose on a body surface area basis) × 5 days every 28 days for three cycles. A no-effect level was not identified.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 Oxaliplatin is combined with Abatacept. Abciximab The risk or severity of hemorrhage can be increased when Oxaliplatin is combined with Abciximab. Abemaciclib Abemaciclib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level. Acebutolol The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Acebutolol. Aceclofenac The risk or severity of nephrotoxicity can be increased when Oxaliplatin is combined with Aceclofenac. - 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Oxaliplatin Solution 5 mg / mL Intravenous Actavis Pharma Company 2015-12-16 2018-07-09 Canada 
Act Oxaliplatin Powder, for solution 50 mg / vial Intravenous Actavis Pharma Company Not applicable Not applicable Canada Act Oxaliplatin Powder, for solution 100 mg / vial Intravenous Actavis Pharma Company Not applicable Not applicable Canada Eloxatin Solution 5 mg / mL Intravenous Sanofi Aventis Deutschland Gmb H 2007-07-17 2018-11-09 Canada Eloxatin Powder, for solution 100 mg/1 Intravenous Sanofi Aventis Deutschland Gmb H 2002-08-09 2009-04-30 US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Oxaliplatin Powder, for solution 100 mg/20mL Intravenous Pfizer Laboratories Div Pfizer Inc 2012-08-09 2016-12-31 US Oxaliplatin Injection, powder, lyophilized, for solution 5 mg/1mL Intravenous Actavis Pharma, Inc. 2015-01-05 2024-08-31 US Oxaliplatin Injection, solution 5 mg/1mL Intravenous Baxter Healthcare Corporation 2018-02-19 Not applicable US Oxaliplatin Injection, solution 5 mg/1mL Intravenous Actavis Pharma, Inc. 2018-08-03 2020-02-29 US Oxaliplatin Injection 100 mg/20mL Intravenous Cipla USA Inc. 2017-02-10 Not applicable US
Categories
- ATC Codes
- L01XA03 — Oxaliplatin
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Coordination Complexes
- Immunosuppressive Agents
- Moderate Risk QTc-Prolonging Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- OCT2 Substrates
- OCT2 Substrates with a Narrow Therapeutic Index
- Platinum Compounds
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclohexylamines. These are organic compounds containing a cyclohexylamine moiety, which consist of a cyclohexane ring attached to an amine group.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Cyclohexylamines
- Direct Parent
- Cyclohexylamines
- Alternative Parents
- Dicarboxylic acids and derivatives / Organic transition metal salts / Carboxylic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic homomonocyclic compound / Amine / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclohexylamine / Dicarboxylic acid or derivatives / Hydrocarbon derivative / Organic oxide / Organic oxygen compound
- Molecular Framework
- Not Available
- External Descriptors
- platinum coordination entity (CHEBI:31941)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 04ZR38536J
- CAS number
- 61825-94-3
- InChI Key
- ZROHGHOFXNOHSO-BNTLRKBRSA-L
- InChI
- InChI=1S/C6H14N2.C2H2O4.Pt/c7-5-3-1-2-4-6(5)8;3-1(4)2(5)6;/h5-6H,1-4,7-8H2;(H,3,4)(H,5,6);/q;;+2/p-2/t5-,6-;;/m1../s1
- IUPAC Name
- (3aR,7aR)-octahydro-2',5'-dioxaspiro[cyclohexa[d]1,3-diaza-2-platinacyclopentane-2,1'-cyclopentane]-3',4'-dione
- SMILES
- [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
References
- Synthesis Reference
Masazumi Eriguchi, "Liposome preparations containing oxaliplatin." U.S. Patent US20040022842, issued February 05, 2004.
US20040022842- General References
- Pasetto LM, D'Andrea MR, Rossi E, Monfardini S: Oxaliplatin-related neurotoxicity: how and why? Crit Rev Oncol Hematol. 2006 Aug;59(2):159-68. Epub 2006 Jun 27. [Article]
- Graham J, Mushin M, Kirkpatrick P: Oxaliplatin. Nat Rev Drug Discov. 2004 Jan;3(1):11-2. [Article]
- Alcindor T, Beauger N: Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol. 2011 Jan;18(1):18-25. doi: 10.3747/co.v18i1.708. [Article]
- FDA Approved Drug Product: ELOXATIN (oxaliplatin) injection, for intravenous use (July 2023) [Link]
- FDA Approved Drug Products: ELOXATIN (oxaliplatin) injection, for intravenous use [Link]
- Oxaliplatin MSDS [Link]
- Sanofi-aventis receives FDA approval for new Eloxatin™ formulation [Link]
- External Links
- KEGG Drug
- D01790
- PubChem Compound
- 6857599
- PubChem Substance
- 46509083
- ChemSpider
- 8062727
- 32592
- ChEBI
- 31941
- ChEMBL
- CHEMBL414804
- Therapeutic Targets Database
- DAP000062
- PharmGKB
- PA131285527
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Oxaliplatin
- FDA label
- Download (2.35 MB)
- MSDS
- Download (38.4 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Colorectal Cancer 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Elderly Metastatic Colorectal Cancer Patients 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Adenocarcinomas of the Gastroesophageal Junction / Gastric Cancer 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Hepatocellular Carcinoma / Injury; Blood Vessel, Hepatic, Artery 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Pancreatic Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Sanofi aventis us llc
- App pharmaceuticals llc
- Ebewe pharma ges mbh nfg kg
- Fresenius kabi oncology plc
- Hospira inc
- Hospira worldwide pty
- Sun pharma global inc
- Teva parenteral medicines inc
- Packagers
- APP Pharmaceuticals
- Ben Venue Laboratories Inc.
- Ebewe Pharma
- Hospira Inc.
- Sanofi-Aventis Inc.
- Sun Pharmaceutical Industries Ltd.
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Solution, concentrate Intravenous 5 mg Solution 100.000 mg Injection, powder, for solution 100 mg Injection, powder, for solution 50 mg Injection, powder, lyophilized, for solution 100 mg Injection, powder, lyophilized, for solution 50 mg Injection, powder, lyophilized, for solution Intravenous 100 mg Injection, solution, concentrate Intravenous Powder, for solution Intravenous 100 mg/1 Powder, for solution Intravenous 5 MG/ML Powder, for solution Intravenous 50 mg/1 Solution Intravenous 5 mg / mL Solution, concentrate Intravenous 200 mg/40mL Solution, concentrate Intravenous 50 mg Injection Intravenous 200 mg/40ml Solution, concentrate Intravenous 100 mg Solution Intravenous 100.000 mg Injection, solution, concentrate Intravenous 150 mg/30ml Solution Intravenous 50 mg/10ml Solution Parenteral 50.000 mg Injection, solution Intravenous Injection Intravenous 100 mg Injection Intravenous 50 mg Solution Intravenous 5 mg Injection Intravenous 100 mg/20mL Injection Intravenous 5 mg/1mL Injection Intravenous 50 mg/10mL Injection, powder, lyophilized, for solution Intravenous 100 mg/20mL Injection, powder, lyophilized, for solution Intravenous 5 mg/1mL Injection, powder, lyophilized, for solution Intravenous 50 mg/10mL Injection, solution Intravenous 100 mg/20mL Injection, solution Intravenous 100 mg/1mL Injection, solution Intravenous 200 mg/40mL Injection, solution Intravenous 5 mg/1mL Injection, solution Intravenous 50 mg/10mL Injection, solution Intravenous 50 mg/1mL Injection, solution, concentrate Intravenous 100 mg/20mL Injection, solution, concentrate Intravenous 5 mg/1mL Injection, solution, concentrate Intravenous 50 mg/10mL Injection; injection, solution, concentrate Intravenous 5 mg/ml Powder, for solution Intravenous 100 mg/20mL Powder, for solution Intravenous 50 mg/10mL Injection, powder, for solution Parenteral Powder, for solution Intravenous 100 mg / vial Powder, for solution Intravenous 50 mg / vial Injection, solution, concentrate Intravenous 5 mg/ml Solution Intravenous 200 mg Injection, solution, concentrate Intravenous 200 mg/40ml Injection, powder, for solution Intravenous 100 mg Powder 100 mg/1vial Solution Intravenous 5 mg/ml Injection, powder, lyophilized, for solution Intravenous 5 mg/ml Injection, powder, lyophilized, for solution Intravenous 10000000 mg Solution Intravenous 100 mg Injection, powder, for solution Intravenous 50 mg Solution Intravenous 50 mg Powder, for solution Intravenous Injection, solution, concentrate Intravenous; Parenteral 5 MG/ML Injection, powder, for solution Intravenous Injection, solution Intravenous 5 MG/ML Injection Intravenous Injection, powder, lyophilized, for solution Parenteral 50 mg Solution Intravenous 50.000 mg Injection, solution Intravenous 2 MG/ML Injection Intravenous 5 mg/ml Injection, powder, lyophilized, for solution Intravenous 200 mg Solution Intravenous 100 mg/20ml Solution Intravenous 200 mg/40ml Solution Parenteral 50.00 mg Solution Intravenous 50.00 mg Injection Intravenous 5 mg Injection, powder, for solution Injection, powder, lyophilized, for solution Intravenous 100.00 mg Injection, powder, lyophilized, for solution Intravenous 50.00 mg Injection, powder, lyophilized, for solution Intravenous 50 mg Solution Intravenous 2 mg/1ml Solution Intravenous 5 mg/1ml Powder 50 mg/1vial Injection, powder, for solution 100 mg/1vial Injection, powder, for solution 50 mg/1vial Injection, solution Intravenous 2 mg/1ml - Prices
Unit description Cost Unit Oxaliplatin 100 mg vial 1650.0USD vial Oxaliplatin 50 mg vial 825.0USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5290961 No 1994-03-01 2013-01-12 US CA2196922 No 2004-06-01 2015-08-07 Canada US5420319 Yes 1995-05-30 2017-02-09 US US5716988 Yes 1998-02-10 2016-02-07 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 100ºC L47311 water solubility 6 mg/mL L47206 - Predicted Properties
Property Value Source Water Solubility 27.5 mg/mL ALOGPS logP -0.47 ALOGPS logS -1.2 ALOGPS Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 0 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 85.82 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 67.52 m3·mol-1 Chemaxon Polarizability 21.9 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 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 + 0.8638 Blood Brain Barrier + 0.7667 Caco-2 permeable - 0.6453 P-glycoprotein substrate Substrate 0.5056 P-glycoprotein inhibitor I Non-inhibitor 0.9332 P-glycoprotein inhibitor II Non-inhibitor 1.0 Renal organic cation transporter Non-inhibitor 0.9289 CYP450 2C9 substrate Non-substrate 0.8846 CYP450 2D6 substrate Non-substrate 0.8094 CYP450 3A4 substrate Non-substrate 0.6064 CYP450 1A2 substrate Non-inhibitor 0.8403 CYP450 2C9 inhibitor Non-inhibitor 0.8686 CYP450 2D6 inhibitor Non-inhibitor 0.8997 CYP450 2C19 inhibitor Non-inhibitor 0.8189 CYP450 3A4 inhibitor Non-inhibitor 0.8337 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9872 Ames test Non AMES toxic 0.6034 Carcinogenicity Non-carcinogens 0.938 Biodegradation Not ready biodegradable 0.9796 Rat acute toxicity 2.3765 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8879 hERG inhibition (predictor II) Non-inhibitor 0.938
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Yes
Adduct
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]
- Sharma S, Gong P, Temple B, Bhattacharyya D, Dokholyan NV, Chaney SG: Molecular dynamic simulations of cisplatin- and oxaliplatin-d(GG) intrastand cross-links reveal differences in their conformational dynamics. J Mol Biol. 2007 Nov 9;373(5):1123-40. Epub 2007 Aug 23. [Article]
- Zhu G, Chang P, Lippard SJ: Recognition of platinum-DNA damage by poly(ADP-ribose) polymerase-1. Biochemistry. 2010 Jul 27;49(29):6177-83. doi: 10.1021/bi100775t. [Article]
- Ramachandran S, Temple BR, Chaney SG, Dokholyan NV: Structural basis for the sequence-dependent effects of platinum-DNA adducts. Nucleic Acids Res. 2009 May;37(8):2434-48. doi: 10.1093/nar/gkp029. Epub 2009 Mar 2. [Article]
- Arango D, Wilson AJ, Shi Q, Corner GA, Aranes MJ, Nicholas C, Lesser M, Mariadason JM, Augenlicht LH: Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells. Br J Cancer. 2004 Nov 29;91(11):1931-46. doi: 10.1038/sj.bjc.6602215. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide
- Specific Function
- glutathione peroxidase activity
- Gene Name
- GSTT1
- Uniprot ID
- P30711
- Uniprot Name
- Glutathione S-transferase theta-1
- Molecular Weight
- 27334.755 Da
References
- Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot MA: Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res. 2006 May 15;12(10):3050-6. doi: 10.1158/1078-0432.CCR-05-2076. [Article]
- Alcindor T, Beauger N: Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol. 2011 Jan;18(1):18-25. doi: 10.3747/co.v18i1.708. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids
- Specific Function
- metal ion binding
- Gene Name
- MT1A
- Uniprot ID
- P04731
- Uniprot Name
- Metallothionein-1A
- Molecular Weight
- 6120.19 Da
References
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids
- Specific Function
- metal ion binding
- Gene Name
- MT2A
- Uniprot ID
- P02795
- Uniprot Name
- Metallothionein-2
- Molecular Weight
- 6042.05 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity (PubMed:9922160). Mediates the proteolytic cleavage of alpha-1-microglobulin to form t-alpha-1-microglobulin, which potently inhibits oxidation of low-density lipoprotein particles and limits vascular damage (PubMed:25698971)
- Specific Function
- chromatin binding
- Gene Name
- MPO
- Uniprot ID
- P05164
- Uniprot Name
- Myeloperoxidase
- Molecular Weight
- 83867.71 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Destroys radicals which are normally produced within the cells and which are toxic to biological systems
- Specific Function
- copper ion binding
- Gene Name
- SOD1
- Uniprot ID
- P00441
- Uniprot Name
- Superoxide dismutase [Cu-Zn]
- Molecular Weight
- 15935.685 Da
References
- Plasencia C, Martinez-Balibrea E, Martinez-Cardus A, Quinn DI, Abad A, Neamati N: Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells. Int J Oncol. 2006 Jul;29(1):225-35. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration
- Specific Function
- dinitrosyl-iron complex binding
- Gene Name
- GSTP1
- Uniprot ID
- P09211
- Uniprot Name
- Glutathione S-transferase P
- Molecular Weight
- 23355.625 Da
References
- Peng Z, Wang Q, Gao J, Ji Z, Yuan J, Tian Y, Shen L: Association between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy: a systematic review and meta-analysis. Cancer Chemother Pharmacol. 2013 Aug;72(2):305-14. doi: 10.1007/s00280-013-2194-x. Epub 2013 May 22. [Article]
- Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot MA: Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res. 2006 May 15;12(10):3050-6. doi: 10.1158/1078-0432.CCR-05-2076. [Article]
- Alcindor T, Beauger N: Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol. 2011 Jan;18(1):18-25. doi: 10.3747/co.v18i1.708. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276)
- Specific Function
- enzyme binding
- Gene Name
- GSTM1
- Uniprot ID
- P09488
- Uniprot Name
- Glutathione S-transferase Mu 1
- Molecular Weight
- 25711.555 Da
References
- Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot MA: Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res. 2006 May 15;12(10):3050-6. doi: 10.1158/1078-0432.CCR-05-2076. [Article]
- Gataa I, Emile G, Loriot MA, Goldwasser F, Alexandre J: Association between high antitumor activity of oxaliplatin and cyclophosphamide and constitutional GSTM1 homozygous deletion in an advanced ovarian cancer patient. Chemotherapy. 2013;59(4):290-3. doi: 10.1159/000357517. Epub 2014 Jan 24. [Article]
- Alcindor T, Beauger N: Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol. 2011 Jan;18(1):18-25. doi: 10.3747/co.v18i1.708. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (By similarity) (PubMed:8999809, PubMed:9271353). Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (PubMed:15102952, PubMed:8999809, PubMed:9271353). Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (PubMed:8999809). Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (PubMed:15687255, PubMed:28291250)
- Specific Function
- cytochrome-b5 reductase activity, acting on NAD(P)H
- Gene Name
- NQO1
- Uniprot ID
- P15559
- Uniprot Name
- NAD(P)H dehydrogenase [quinone] 1
- Molecular Weight
- 30867.405 Da
References
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Schueffl H, Theiner S, Hermann G, Mayr J, Fronik P, Groza D, van Schonhooven S, Galvez L, Sommerfeld NS, Schintlmeister A, Reipert S, Wagner M, Mader RM, Koellensperger G, Keppler BK, Berger W, Kowol CR, Legin A, Heffeter P: Albumin-targeting of an oxaliplatin-releasing platinum(iv) prodrug results in pronounced anticancer activity due to endocytotic drug uptake in vivo. Chem Sci. 2021 Aug 26;12(38):12587-12599. doi: 10.1039/d1sc03311e. eCollection 2021 Oct 6. [Article]
- FDA Approved Drug Product: ELOXATIN (oxaliplatin) injection, for intravenous use (July 2023) [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Burger H, Zoumaro-Djayoon A, Boersma AW, Helleman J, Berns EM, Mathijssen RH, Loos WJ, Wiemer EA: Differential transport of platinum compounds by the human organic cation transporter hOCT2 (hSLC22A2). Br J Pharmacol. 2010 Feb;159(4):898-908. doi: 10.1111/j.1476-5381.2009.00569.x. Epub 2010 Jan 8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Uniporter that mediates the transport of copper(1+) from the extracellular space to the cytoplasm, across the plasma membrane (PubMed:11734551, PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, PubMed:20569931, PubMed:23658018) and delivers directly copper(1+) to specific chaperone such as ATOX1, via a copper(1+)- mediated transient interaction between the C-terminal domain and a copper(1+) chaperone, thus controlling intracellular copper(1+) levels (PubMed:11734551, PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, PubMed:20569931, PubMed:23658018, PubMed:26745413). May function in copper(1+) import from the apical membrane thus may drive intestinal copper absorption (By similarity). The copper(1+) transport mechanism is sodium-independent, saturable and of high-affinity (PubMed:11734551). Also mediates the uptake of silver(1+) (PubMed:20569931). May function in the influx of the platinum-containing chemotherapeutic agents (PubMed:20451502, PubMed:20569931). The platinum-containing chemotherapeutic agents uptake is saturable (By similarity). In vitro, mediates the transport of cadmium(2+) into cells (PubMed:33294387). Also participates in the first step of copper(2+) acquisition by cells through a direct transfer of copper(2+) from copper(2+) carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper(2+) reduction and probably followed by copper(1+) stabilization (PubMed:30489586). In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper(1+) transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-189 leadin g to a subsequent disulfide bond formation between SLC31A1 and KDR (PubMed:35027734). The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (PubMed:35027734)
- Specific Function
- copper ion binding
- Gene Name
- SLC31A1
- Uniprot ID
- O15431
- Uniprot Name
- High affinity copper uptake protein 1
- Molecular Weight
- 21090.545 Da
References
- Howell SB, Safaei R, Larson CA, Sailor MJ: Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs. Mol Pharmacol. 2010 Jun;77(6):887-94. doi: 10.1124/mol.109.063172. Epub 2010 Feb 16. [Article]
- Song IS, Savaraj N, Siddik ZH, Liu P, Wei Y, Wu CJ, Kuo MT: Role of human copper transporter Ctr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant cells. Mol Cancer Ther. 2004 Dec;3(12):1543-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity)
- Specific Function
- monoamine transmembrane transporter activity
- Gene Name
- SLC22A3
- Uniprot ID
- O75751
- Uniprot Name
- Solute carrier family 22 member 3
- Molecular Weight
- 61279.485 Da
References
- Yokoo S, Masuda S, Yonezawa A, Terada T, Katsura T, Inui K: Significance of organic cation transporter 3 (SLC22A3) expression for the cytotoxic effect of oxaliplatin in colorectal cancer. Drug Metab Dispos. 2008 Nov;36(11):2299-306. doi: 10.1124/dmd.108.023168. Epub 2008 Aug 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Ceckova M, Vackova Z, Radilova H, Libra A, Buncek M, Staud F: Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP. Toxicol In Vitro. 2008 Dec;22(8):1846-52. doi: 10.1016/j.tiv.2008.09.001. Epub 2008 Sep 9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Biswas R, Bugde P, He J, Merien F, Lu J, Liu DX, Myint K, Liu J, McKeage M, Li Y: Transport-Mediated Oxaliplatin Resistance Associated with Endogenous Overexpression of MRP2 in Caco-2 and PANC-1 Cells. Cancers (Basel). 2019 Sep 8;11(9):1330. doi: 10.3390/cancers11091330. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into the bile in response to copper overload
- Specific Function
- ATP binding
- Gene Name
- ATP7B
- Uniprot ID
- P35670
- Uniprot Name
- Copper-transporting ATPase 2
- Molecular Weight
- 157261.34 Da
References
- Martinez-Balibrea E, Martinez-Cardus A, Musulen E, Gines A, Manzano JL, Aranda E, Plasencia C, Neamati N, Abad A: Increased levels of copper efflux transporter ATP7B are associated with poor outcome in colorectal cancer patients receiving oxaliplatin-based chemotherapy. Int J Cancer. 2009 Jun 15;124(12):2905-10. doi: 10.1002/ijc.24273. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:10419525, PubMed:19453293, PubMed:19917612, PubMed:28389643, PubMed:31283225). Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway (PubMed:11092760, PubMed:28389643). Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions (PubMed:10419525, PubMed:28389643). May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (By similarity) (PubMed:28389643). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity)
- Specific Function
- ATP binding
- Gene Name
- ATP7A
- Uniprot ID
- Q04656
- Uniprot Name
- Copper-transporting ATPase 1
- Molecular Weight
- 163371.335 Da
References
- Samimi G, Safaei R, Katano K, Holzer AK, Rochdi M, Tomioka M, Goodman M, Howell SB: Increased expression of the copper efflux transporter ATP7A mediates resistance to cisplatin, carboplatin, and oxaliplatin in ovarian cancer cells. Clin Cancer Res. 2004 Jul 15;10(14):4661-9. doi: 10.1158/1078-0432.CCR-04-0137. [Article]
- PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Drug created at June 13, 2005 13:24 / Updated at October 11, 2024 18:19