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Identification
NameCisplatin
Accession NumberDB00515  (APRD00359)
TypeSmall Molecule
GroupsApproved
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
Thumb
Synonyms
SynonymLanguageCode
CDDPNot AvailableNot Available
Cis-DDPNot AvailableNot Available
cis-diamminedichloroplatinum(II)Not AvailableNot Available
Platinol-AQNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AbiplatinNot Available
CisplatylNot Available
PlatidiamNot Available
PlatinCadila Healthcare
PlatinolNot Available
Brand mixturesNot Available
Categories
CAS number15663-27-1
WeightAverage: 298.035
Monoisotopic: 296.939928001
Chemical FormulaCl2H4N2Pt
InChI KeyDQLATGHUWYMOKM-UHFFFAOYSA-L
InChI
InChI=1S/2ClH.2H2N.Pt/h2*1H;2*1H2;/q;;2*-1;+4/p-2
IUPAC Name
dichloroplatinumdiamine
SMILES
N[Pt](N)(Cl)Cl
Mass SpecNot Available
Taxonomy
KingdomInorganic Compounds
SuperclassMixed Metal/Non-metal Compounds
ClassTransition Metal Salts
SubclassTransition Metal Chlorides
Direct parentTransition Metal Chlorides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionThis compound belongs to the transition metal chlorides. These are inorganic compounds in which the largest halogen atom is Chlorine, and the heaviest metal atom is a transition metal.
Pharmacology
IndicationFor the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.
PharmacodynamicsCisplatin 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 actionAlkylating 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.
AbsorptionFollowing cisplatin doses of 20 to 120 mg/m^2, the concentrations of platinum are highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen; and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration.
Volume of distribution

Volume of distribution at steady state = 11-12 L/m^2

Protein bindingCisplatin does not undergo instantaneous and reversible binding to plasma protein that is characteristic of normal drug-protein binding. However, the platinum itself is capable of binding to plasma proteins, including albumin, transferrin, and gamma globulin. Three hours after a bolus injection and two hours after the end of a three-hour infusion, 90% of the plasma platinum is protein bound.
Metabolism
Route of eliminationThe 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 lifeCisplatin decays monoexponentially with a half life of 20 to 30 minutes following administrations of 50 or 100 mg/m^2. Cisplatin has a plasma half-life of 30 minutes. The complexes between albumin and the platinum from cisplatin do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more.
Clearance
  • 15-16 L/h/m^2 [total body clearance, 7-hour infusion of 100 mg/m^2]
  • 62 mL/min/m^2 [renal clearance, 2-hour infusion of 100 mg/m^2]
  • 50 mL/min/m^2 [renal clearance, 6- to 7-hour infusion of 100 mg/m^2]
    The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption.
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Glutathione S-transferase Mu 1
Gene symbol: GSTM1
UniProt: P09488
Not AvailableGSTM1presenceTinnitus, hearing impairment, Raynaud syndrome18162130
Low-density lipoprotein receptor-related protein 2
Gene symbol: LRP2
UniProt: P98164
rs2075252 Not AvailableA alleleOtotoxicity (hearing loss)17457342
Low-density lipoprotein receptor-related protein 2
Gene symbol: LRP2
UniProt: P98164
rs4668123 Not AvailableT alleleOtotoxicity (hearing loss)17457342
Glutathione S-transferase P
Gene symbol: GSTP1
UniProt: P09211
rs1695 Not AvailableA alleleTinnitus, hearing impairment, Raynaud syndrome18162130
DNA repair protein complementing XP-C cells
Gene symbol: XPC
UniProt: Q01831
rs2228001 Not AvailableG > TThose with the GG or GT genotpe have an increase risk of adverse effects21047201
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9637
Blood Brain Barrier + 0.9469
Caco-2 permeable - 0.5704
P-glycoprotein substrate Non-substrate 0.8714
P-glycoprotein inhibitor I Non-inhibitor 0.9763
P-glycoprotein inhibitor II Non-inhibitor 0.9843
Renal organic cation transporter Non-inhibitor 0.9211
CYP450 2C9 substrate Non-substrate 0.8069
CYP450 2D6 substrate Non-substrate 0.7874
CYP450 3A4 substrate Non-substrate 0.7495
CYP450 1A2 substrate Non-inhibitor 0.7733
CYP450 2C9 substrate Non-inhibitor 0.7808
CYP450 2D6 substrate Non-inhibitor 0.9075
CYP450 2C19 substrate Non-inhibitor 0.7995
CYP450 3A4 substrate Non-inhibitor 0.8562
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9204
Ames test Non AMES toxic 0.5661
Carcinogenicity Carcinogens 0.5146
Biodegradation Not ready biodegradable 0.9213
Rat acute toxicity 2.7612 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9774
hERG inhibition (predictor II) Non-inhibitor 0.9344
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Pharmachemie bv
  • Teva parenteral medicines inc
  • Bristol myers co
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Cisplatin 1 mg/ml vial0.41USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point270 dec °CPhysProp
water solubility2530 mg/L (at 25 °C)AMUNDSEN,AR & STERN,EW (1982)
logP-2.19HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
logP0.041ChemAxon
pKa (Strongest Basic)5.06ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area52.04 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity22.84 m3·mol-1ChemAxon
Polarizability10.31 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Murray A. Kaplan, Alphonse P. Granatek, “Process for the preparation of microcrystalline cisplatin.” U.S. Patent US4322391, issued March 30, 1982.

US4322391
General Reference
  1. FDA label
External Links
ResourceLink
KEGG DrugD00275
KEGG CompoundC06911
PubChem Compound441203
PubChem Substance46504561
ChemSpider389985
ChEBI27899
ChEMBLCHEMBL2068237
Therapeutic Targets DatabaseDAP000215
PharmGKBPA449014
Drug Product Database2126613
RxListhttp://www.rxlist.com/cgi/generic3/cisplatin.htm
Drugs.comhttp://www.drugs.com/cdi/cisplatin.html
WikipediaCisplatin
ATC CodesL01XA01
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelshow(413 KB)
MSDSshow(76.1 KB)
Interactions
Drug Interactions
Drug
AmikacinIncreased risk of nephrotoxicity
BendamustineIncreases toxicity through pharmacodynamic synergism. Additive myelosuppression.
BumetanideIncreased ototoxicity
CabazitaxelPlatinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as cabazitaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity.Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
DocetaxelPlatinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as docetaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
Ethacrynic acidIncreased ototoxicity
FosphenytoinThe antineoplasic agent decreases the effect of hydantoin
FurosemideIncreased ototoxicity
GentamicinIncreased risk of nephrotoxicity
LeflunomideImmunosuppressants such as cisplatin may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
MethotrexateCisplatin increases methotrexate toxicity
NatalizumabImmunosuppressants such as cisplatin may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
NetilmicinIncreased risk of nephrotoxicity
PaclitaxelCisplatin increases the effect and toxicity of paclitaxel
PhenytoinThe antineoplasic agent decreases the effect of hydantoin
PimecrolimusPimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cisplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
RoflumilastRoflumilast may enhance the immunosuppressive effect of immunosuppressants such as cisplatin. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
TacrolimusAdditive renal impairment may occur during concomitant therapy with aminoglycosides such as Cisplatin. Use caution during concomitant therapy.
TobramycinIncreased risk of nephrotoxicity
TopotecanAdministration of Topotecan after Cisplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
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

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: cross-linking/alkylation

Components

Name UniProt ID Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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
  4. 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
  5. 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

Enzymes

1. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. Erdogan S, Tosyali E, Duzguner V, Kucukgul A, Aslantas O, Celik S: Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production. Res Vet Sci. 2010 Apr;88(2):218-26. Epub 2009 Oct 8. Pubmed
  2. Ozen S, Akyol O, Iraz M, Sogut S, Ozugurlu F, Ozyurt H, Odaci E, Yildirim Z: Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats. J Appl Toxicol. 2004 Jan-Feb;24(1):27-35. Pubmed

2. Xanthine dehydrogenase/oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Xanthine dehydrogenase/oxidase P47989 Details

References:

  1. Yilmaz HR, Sogut S, Ozyurt B, Ozugurlu F, Sahin S, Isik B, Uz E, Ozyurt H: The activities of liver adenosine deaminase, xanthine oxidase, catalase, superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl ester. Toxicol Ind Health. 2005 May;21(3-4):67-73. Pubmed
  2. Cetin R, Devrim E, Kilicoglu B, Avci A, Candir O, Durak I: Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods. J Appl Toxicol. 2006 Jan-Feb;26(1):42-6. Pubmed
  3. Erdogan S, Tosyali E, Duzguner V, Kucukgul A, Aslantas O, Celik S: Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production. Res Vet Sci. 2010 Apr;88(2):218-26. Epub 2009 Oct 8. Pubmed

3. Cytochrome P450 4A11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 4A11 Q02928 Details

References:

  1. Nakamura M, Imaoka S, Tanaka E, Misawa S, Funae Y: cis-Diamminedichloroplatinum induces peroxisomes as well as CYP4A1 in rat kidney. Res Commun Mol Pathol Pharmacol. 1998 Jan;99(1):23-32. Pubmed

4. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Tusgaard B, Norregaard R, Jensen AM, Wang G, Topcu SO, Wang Y, Nielsen S, Frokiaer J: Cisplatin decreases renal cyclooxygenase-2 expression and activity in rats. Acta Physiol (Oxf). 2011 May;202(1):79-90. doi: 10.1111/j.1748-1716.2011.02257.×. Epub 2011 Mar 22. Pubmed]

5. Arylamine N-acetyltransferase

Kind: protein

Organism: Mycobacterium tuberculosis

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Arylamine N-acetyltransferase P0A5L8 Details

References:

  1. Ragunathan N, Dairou J, Pluvinage B, Martins M, Petit E, Janel N, Dupret JM, Rodrigues-Lima F: Identification of the xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 as a new target of cisplatin in breast cancer cells: molecular and cellular mechanisms of inhibition. Mol Pharmacol. 2008 Jun;73(6):1761-8. Epub 2008 Feb 29. Pubmed
  2. Holzer AK, Samimi G, Katano K, Naerdemann W, Lin X, Safaei R, Howell SB: The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells. Mol Pharmacol. 2004 Oct;66(4):817-23. Epub 2004 Jun 30. Pubmed
  3. Holzer AK, Samimi G, Katano K, Naerdemann W, Lin X, Safaei R, Howell SB: The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells. Mol Pharmacol. 2004 Oct;66(4):817-23. Epub 2004 Jun 30. Pubmed
  4. Holzer AK, Samimi G, Katano K, Naerdemann W, Lin X, Safaei R, Howell SB: The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells. Mol Pharmacol. 2004 Oct;66(4):817-23. Epub 2004 Jun 30. Pubmed
  5. Holzer AK, Samimi G, Katano K, Naerdemann W, Lin X, Safaei R, Howell SB: The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells. Mol Pharmacol. 2004 Oct;66(4):817-23. Epub 2004 Jun 30. Pubmed

6. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Masek V, Anzenbacherova E, Machova M, Brabec V, Anzenbacher P: Interaction of antitumor platinum complexes with human liver microsomal cytochromes P450. Anticancer Drugs. 2009 Jun;20(5):305-11. Pubmed

7. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Masek V, Anzenbacherova E, Machova M, Brabec V, Anzenbacher P: Interaction of antitumor platinum complexes with human liver microsomal cytochromes P450. Anticancer Drugs. 2009 Jun;20(5):305-11. Pubmed

8. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. Bodur E: Human serum butyrylcholinesterase interactions with cisplatin and cyclophosphamide. Biochimie. 2010 Aug;92(8):979-84. Epub 2010 Apr 24. Pubmed

9. Glutathione S-transferase theta-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Glutathione S-transferase theta-1 P30711 Details

References:

  1. Peters U, Preisler-Adams S, Hebeisen A, Hahn M, Seifert E, Lanvers C, Heinecke A, Horst J, Jurgens H, Lamprecht-Dinnesen A: Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Anticancer Drugs. 2000 Sep;11(8):639-43. Pubmed

10. Metallothionein-1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Metallothionein-1A P04731 Details

References:

  1. Meijer C, Timmer A, De Vries EG, Groten JP, Knol A, Zwart N, Dam WA, Sleijfer DT, Mulder NH: Role of metallothionein in cisplatin sensitivity of germ-cell tumours. Int J Cancer. 2000 Mar 15;85(6):777-81. Pubmed

11. Metallothionein-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Metallothionein-2 P02795 Details

References:

  1. Meijer C, Timmer A, De Vries EG, Groten JP, Knol A, Zwart N, Dam WA, Sleijfer DT, Mulder NH: Role of metallothionein in cisplatin sensitivity of germ-cell tumours. Int J Cancer. 2000 Mar 15;85(6):777-81. Pubmed

12. Superoxide dismutase [Cu-Zn]

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Superoxide dismutase [Cu-Zn] P00441 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262

13. Glutathione S-transferase P

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Glutathione S-transferase P P09211 Details

References:

  1. Peters U, Preisler-Adams S, Hebeisen A, Hahn M, Seifert E, Lanvers C, Heinecke A, Horst J, Jurgens H, Lamprecht-Dinnesen A: Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Anticancer Drugs. 2000 Sep;11(8):639-43. Pubmed

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
NAD(P)H dehydrogenase [quinone] 1 P15559 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262

15. Glutathione S-transferase Mu 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Glutathione S-transferase Mu 1 P09488 Details

References:

  1. Peters U, Preisler-Adams S, Hebeisen A, Hahn M, Seifert E, Lanvers C, Heinecke A, Horst J, Jurgens H, Lamprecht-Dinnesen A: Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Anticancer Drugs. 2000 Sep;11(8):639-43. Pubmed

Transporters

1. Canalicular multispecific organic anion transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 2 O15438 Details

References:

  1. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Multidrug resistance-associated protein 5 O15440 Details

References:

  1. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. 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. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. 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
  2. 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
  3. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
High affinity copper uptake protein 1 O15431 Details

References:

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Holzer, A.K. et al. The copper influx transporter human copper transport
    protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells.
    Mol Pharmacol 66, 817-823 (2004).Pubmed

6. Probable low affinity copper uptake protein 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Probable low affinity copper uptake protein 2 O15432 Details

References:

  1. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 6 O95255 Details

References:

  1. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Copper-transporting ATPase 2 P35670 Details

References:

  1. 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
  2. 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
  3. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Copper-transporting ATPase 1 Q04656 Details

References:

  1. 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
  2. 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

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. 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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11