DrugBank: Cisplatin (DB00515)

targets (1) transporters (10)

Identification

Name

Cisplatin

Accession Number

DB00515 (APRD00359)

Type

small molecule

Groups

approved

Description

Cisplatin, cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

CACP
Cis-DDP
Cis-Diaminedichloroplatinum
Cis-Diamminedichloroplatinum
CPDC
CPDD
DDP
DDPT
Diamminedichloroplatinum
Platinum Ammine Chloride
Platinum Ammonium Chloride
Platinum Diamine Dichloride
Trans-DDP
Trans-Diaminedichloroplatinum
Trans-Diamminedichloroplatinum
Trans-Dichlorodiammine Platinum
Trans-Platinumdiammine Dichloride

Brand names

Abiplatin
Biocisplatinum
Briplatin
Carboquone
Cis Pt II
Cismaplat
Cisplatine
Cisplatyl
Citoplationo
Lederplatin
Neoplatin
Plastin
Platamine
Platiblastin
Platidiam
Platinex
Platinol
Platinol-AQ
Platinoxan
Randa

Brand name mixtures

Not Available

Categories

Antineoplastic Agents
Radiation-Sensitizing Agents
Cross-Linking Reagents

CAS number

15663-27-1

Weight

Average: 300.051
Monoisotopic: 55.28

Chemical Formula

Cl₂H₆N₂Pt

InChI Key

InChIKey=LXZZYRPGZAFOLE-UHFFFAOYSA-L

InChI

InChI=1S/2ClH.2H3N.Pt/h2*1H;2*1H3;/q;;;;+2/p-2

Plain Text

IUPAC Name

dichloroplatinumdiamine

SMILES

N[Pt](N)(Cl)Cl

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Inorganic

Classes

Inorganic Ions and Gases

Substructures

Cations
Inorganic Ions and Gases

Pharmacology

Indication

For the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.

Pharmacodynamics

Cisplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.

Mechanism of action

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Greater than 90%.

Metabolism

Route of elimination

The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant.

Half life

20-30 minutes

Clearance

15 – 16 L/h/m2 [After infusions of 100 mg/m2.]

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

App pharmaceuticals llc
Bedford laboratories div ben venue laboratories inc
Pharmachemie bv
Teva parenteral medicines inc
Bristol myers co

Packagers

Dosage forms

Form	Route	Strength
Solution	Intravenous

Prices

Unit description	Cost	Unit
Cisplatin 1 mg/ml vial	0.41 USD	ml

Patents

Not Available

Properties

State

solid

Melting point

270 oC

Experimental Properties

Property	Value	Source
water solubility	2530 mg/L	PhysProp
logP	-2.19	PhysProp

Predicted Properties

Property	Value	Source
water solubility		ALOGPS
logP		ALOGPS
logP	0	ChemAxon Molconvert
logS		ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	43	ChemAxon Molconvert
hydrogen donor count	11	ChemAxon Molconvert
polar surface area		ChemAxon Molconvert
rotatable bond count		ChemAxon Molconvert
refractivity		ChemAxon Molconvert
polarizability		ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00275
KEGG Compound	C06911
PubChem Compound	441203
PubChem Substance	46504561
ChemSpider	389985
ChEBI	27899
ChEMBL	27899
Therapeutic Targets Database	DAP000215
PharmGKB	PA449014
Drug Product Database	2126613
RxList	http://www.rxlist.com/cgi/generic3/cisplatin.htm
Drugs.com	http://www.drugs.com/cdi/cisplatin.html
Wikipedia	http://en.wikipedia.org/wiki/Cisplatin

ATC Codes

L01XA01

AHFS Codes

10:00.00

PDB Entries

Not Available

FDA label

show (413 KB)

MSDS

show (76.1 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

Targets
1. DNA Pharmacological action: yes Actions: cross-linking/alkylation DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes. Gene Sequence: FASTA References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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. Pubmed Garcia Sar D, Montes-Bayon M, Aguado Ortiz L, Blanco-Gonzalez E, Sierra LM, Sanz-Medel A: In vivo detection of DNA adducts induced by cisplatin using capillary HPLC-ICP-MS and their correlation with genotoxic damage in Drosophila melanogaster. Anal Bioanal Chem. 2007 Oct 12;. Pubmed 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 Aug 23;. Pubmed Bloemink MJ, Reedijk J: Cisplatin and derived anticancer drugs: mechanism and current status of DNA binding. Met Ions Biol Syst. 1996;32:641-85. Pubmed

Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

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

Gene Sequence: FASTA

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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. Pubmed
Garcia Sar D, Montes-Bayon M, Aguado Ortiz L, Blanco-Gonzalez E, Sierra LM, Sanz-Medel A: In vivo detection of DNA adducts induced by cisplatin using capillary HPLC-ICP-MS and their correlation with genotoxic damage in Drosophila melanogaster. Anal Bioanal Chem. 2007 Oct 12;. Pubmed
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 Aug 23;. Pubmed
Bloemink MJ, Reedijk J: Cisplatin and derived anticancer drugs: mechanism and current status of DNA binding. Met Ions Biol Syst. 1996;32:641-85. Pubmed

Transporters
1. Canalicular multispecific organic anion transporter 2 Actions: inducer May act as an inducible transporter in the biliary and intestinal excretion of organic anions UniProt ID: O15438 Gene: ABCC3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed 2. Multidrug resistance-associated protein 5 Actions: inducer Acts as a multispecific organic anion pump which can transport nucleotide analogs UniProt ID: O15440 Gene: ABCC5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed 3. Canalicular multispecific organic anion transporter 1 Actions: inducer Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter UniProt ID: Q92887 Gene: ABCC2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed Demeule M, Brossard M, Beliveau R: Cisplatin induces renal expression of P-glycoprotein and canalicular multispecific organic anion transporter. Am J Physiol. 1999 Dec;277(6 Pt 2):F832-40. Pubmed 4. Solute carrier family 22 member 2 Actions: substrate, inhibitor Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity UniProt ID: O15244 Gene: SLC22A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA: A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999 Feb;47(2):181-6. Pubmed 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. Epub 2010 Jan 8. Pubmed Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed 5. High affinity copper uptake protein 1 Actions: substrate Involved in high-affinity copper uptake UniProt ID: O15431 Gene: SLC31A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Epub 2010 Feb 16. Pubmed Kurokawa T, He G, Siddik ZH: Protein kinase inhibitors emodin and dichloro-ribofuranosylbenzimidazole modulate the cellular accumulation and cytotoxicity of cisplatin in a schedule-dependent manner. Cancer Chemother Pharmacol. 2010 Feb;65(3):427-36. Epub 2009 Jun 16. Pubmed Jandial DD, Farshchi-Heydari S, Larson CA, Elliott GI, Wrasidlo WJ, Howell SB: Enhanced delivery of cisplatin to intraperitoneal ovarian carcinomas mediated by the effects of bortezomib on the human copper transporter 1. Clin Cancer Res. 2009 Jan 15;15(2):553-60. Pubmed Liang ZD, Stockton D, Savaraj N, Tien Kuo M: Mechanistic comparison of human high-affinity copper transporter 1-mediated transport between copper ion and cisplatin. Mol Pharmacol. 2009 Oct;76(4):843-53. Epub 2009 Jul 1. Pubmed Rabik CA, Maryon EB, Kasza K, Shafer JT, Bartnik CM, Dolan ME: Role of copper transporters in resistance to platinating agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):133-42. Epub 2008 Nov 8. Pubmed Pabla N, Murphy RF, Liu K, Dong Z: The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol. 2009 Mar;296(3):F505-11. Epub 2009 Jan 14. Pubmed Furukawa T, Komatsu M, Ikeda R, Tsujikawa K, Akiyama S: Copper transport systems are involved in multidrug resistance and drug transport. Curr Med Chem. 2008;15(30):3268-78. Pubmed 6. Probable low affinity copper uptake protein 2 Actions: substrate Involved in low-affinity copper uptake (Potential) UniProt ID: O15432 Gene: SLC31A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Blair BG, Larson CA, Safaei R, Howell SB: Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res. 2009 Jul 1;15(13):4312-21. Epub 2009 Jun 9. Pubmed 7. Multidrug resistance-associated protein 6 Actions: substrate May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS) UniProt ID: O95255 Gene: ABCC6 Protein Sequence: FASTA SNPs: SNPJam Report References: Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. Pubmed 8. Multidrug resistance protein 1 Actions: substrate Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. Pubmed 9. Copper-transporting ATPase 2 Actions: substrate Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile UniProt ID: P35670 Gene: ATP7B Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Rabik CA, Maryon EB, Kasza K, Shafer JT, Bartnik CM, Dolan ME: Role of copper transporters in resistance to platinating agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):133-42. Epub 2008 Nov 8. Pubmed Mangala LS, Zuzel V, Schmandt R, Leshane ES, Halder JB, Armaiz-Pena GN, Spannuth WA, Tanaka T, Shahzad MM, Lin YG, Nick AM, Danes CG, Lee JW, Jennings NB, Vivas-Mejia PE, Wolf JK, Coleman RL, Siddik ZH, Lopez-Berestein G, Lutsenko S, Sood AK: Therapeutic Targeting of ATP7B in Ovarian Carcinoma. Clin Cancer Res. 2009 Jun 1;15(11):3770-80. Epub 2009 May 26. Pubmed Furukawa T, Komatsu M, Ikeda R, Tsujikawa K, Akiyama S: Copper transport systems are involved in multidrug resistance and drug transport. Curr Med Chem. 2008;15(30):3268-78. Pubmed 10. Copper-transporting ATPase 1 Actions: substrate May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells UniProt ID: Q04656 Gene: ATP7A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Rabik CA, Maryon EB, Kasza K, Shafer JT, Bartnik CM, Dolan ME: Role of copper transporters in resistance to platinating agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):133-42. Epub 2008 Nov 8. Pubmed Furukawa T, Komatsu M, Ikeda R, Tsujikawa K, Akiyama S: Copper transport systems are involved in multidrug resistance and drug transport. Curr Med Chem. 2008;15(30):3268-78. Pubmed

Transporters

1. Canalicular multispecific organic anion transporter 2

Actions: inducer

May act as an inducible transporter in the biliary and intestinal excretion of organic anions

UniProt ID: O15438 Link_out

Gene: ABCC3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed

2. Multidrug resistance-associated protein 5

Actions: inducer

Acts as a multispecific organic anion pump which can transport nucleotide analogs

UniProt ID: O15440 Link_out

Gene: ABCC5 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed

3. Canalicular multispecific organic anion transporter 1

Actions: inducer

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out

Gene: ABCC2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. Pubmed
Demeule M, Brossard M, Beliveau R: Cisplatin induces renal expression of P-glycoprotein and canalicular multispecific organic anion transporter. Am J Physiol. 1999 Dec;277(6 Pt 2):F832-40. Pubmed

4. Solute carrier family 22 member 2

Actions: substrate, inhibitor

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out

Gene: SLC22A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA: A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999 Feb;47(2):181-6. Pubmed
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. Epub 2010 Jan 8. Pubmed
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

5. High affinity copper uptake protein 1

Actions: substrate

Involved in high-affinity copper uptake

UniProt ID: O15431 Link_out

Gene: SLC31A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2010 Feb 16. Pubmed
Kurokawa T, He G, Siddik ZH: Protein kinase inhibitors emodin and dichloro-ribofuranosylbenzimidazole modulate the cellular accumulation and cytotoxicity of cisplatin in a schedule-dependent manner. Cancer Chemother Pharmacol. 2010 Feb;65(3):427-36. Epub 2009 Jun 16. Pubmed
Jandial DD, Farshchi-Heydari S, Larson CA, Elliott GI, Wrasidlo WJ, Howell SB: Enhanced delivery of cisplatin to intraperitoneal ovarian carcinomas mediated by the effects of bortezomib on the human copper transporter 1. Clin Cancer Res. 2009 Jan 15;15(2):553-60. Pubmed
Liang ZD, Stockton D, Savaraj N, Tien Kuo M: Mechanistic comparison of human high-affinity copper transporter 1-mediated transport between copper ion and cisplatin. Mol Pharmacol. 2009 Oct;76(4):843-53. Epub 2009 Jul 1. Pubmed
Rabik CA, Maryon EB, Kasza K, Shafer JT, Bartnik CM, Dolan ME: Role of copper transporters in resistance to platinating agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):133-42. Epub 2008 Nov 8. Pubmed
Pabla N, Murphy RF, Liu K, Dong Z: The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol. 2009 Mar;296(3):F505-11. Epub 2009 Jan 14. Pubmed
Furukawa T, Komatsu M, Ikeda R, Tsujikawa K, Akiyama S: Copper transport systems are involved in multidrug resistance and drug transport. Curr Med Chem. 2008;15(30):3268-78. Pubmed

6. Probable low affinity copper uptake protein 2

Actions: substrate

Involved in low-affinity copper uptake (Potential)

UniProt ID: O15432 Link_out

Gene: SLC31A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Blair BG, Larson CA, Safaei R, Howell SB: Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res. 2009 Jul 1;15(13):4312-21. Epub 2009 Jun 9. Pubmed

7. Multidrug resistance-associated protein 6

Actions: substrate

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS)

UniProt ID: O95255 Link_out

Gene: ABCC6 Link_out

Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. Pubmed

8. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. Pubmed

9. Copper-transporting ATPase 2

Actions: substrate

Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile

UniProt ID: P35670 Link_out

Gene: ATP7B Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Rabik CA, Maryon EB, Kasza K, Shafer JT, Bartnik CM, Dolan ME: Role of copper transporters in resistance to platinating agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):133-42. Epub 2008 Nov 8. Pubmed
Mangala LS, Zuzel V, Schmandt R, Leshane ES, Halder JB, Armaiz-Pena GN, Spannuth WA, Tanaka T, Shahzad MM, Lin YG, Nick AM, Danes CG, Lee JW, Jennings NB, Vivas-Mejia PE, Wolf JK, Coleman RL, Siddik ZH, Lopez-Berestein G, Lutsenko S, Sood AK: Therapeutic Targeting of ATP7B in Ovarian Carcinoma. Clin Cancer Res. 2009 Jun 1;15(11):3770-80. Epub 2009 May 26. Pubmed
Furukawa T, Komatsu M, Ikeda R, Tsujikawa K, Akiyama S: Copper transport systems are involved in multidrug resistance and drug transport. Curr Med Chem. 2008;15(30):3268-78. Pubmed

10. Copper-transporting ATPase 1

Actions: substrate

May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells

UniProt ID: Q04656 Link_out

Gene: ATP7A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Rabik CA, Maryon EB, Kasza K, Shafer JT, Bartnik CM, Dolan ME: Role of copper transporters in resistance to platinating agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):133-42. Epub 2008 Nov 8. Pubmed
Furukawa T, Komatsu M, Ikeda R, Tsujikawa K, Akiyama S: Copper transport systems are involved in multidrug resistance and drug transport. Curr Med Chem. 2008;15(30):3268-78. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on August 01, 2011 00:14

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.