Cisplatin (T3D4686)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-09-11 02:04:56 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4686
Identification
Common NameCisplatin
ClassSmall Molecule
DescriptionCisplatin, 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.
Compound Type
  • Antineoplastic Agent
  • Cross-Linking Reagent
  • Drug
  • Inorganic Compound
  • Metabolite
  • Radiation-Sensitizing Agent
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
CDDP
Cis-DDP
Cisplatyl
Platidiam
Trans-DDP
Chemical FormulaCl2H4N2Pt
Average Molecular Mass298.035 g/mol
Monoisotopic Mass296.940 g/mol
CAS Registry Number15663-27-1
IUPAC Namedichloroplatinumdiamine
Traditional Namediamminedichloroplatinum
SMILES[NH2-].[NH2-].[Cl-].[Cl-].[Pt+4]
InChI IdentifierInChI=1S/2ClH.2H2N.Pt/h2*1H;2*1H2;/q;;2*-1;+4/p-2
InChI KeyInChIKey=DQLATGHUWYMOKM-UHFFFAOYSA-L
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as transition metal chlorides. These are inorganic compounds in which the largest halogen atom is Chlorine, and the heaviest metal atom is a transition metal.
KingdomInorganic compounds
Super ClassMixed metal/non-metal compounds
ClassTransition metal salts
Sub ClassTransition metal chlorides
Direct ParentTransition metal chlorides
Alternative Parents
Substituents
  • Transition metal chloride
  • Inorganic chloride salt
  • Inorganic salt
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point270°C
Boiling PointNot Available
Solubility2530 mg/L (at 25°C)
LogP-2.19
Predicted Properties
PropertyValueSource
logP0.041ChemAxon
pKa (Strongest Basic)5.06ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area52.04 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity22.84 m³·mol⁻¹ChemAxon
Polarizability10.31 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03di-0090000000-793238d3cfc8d79400ef2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-0c2078f0dc6f7b75613b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0090000000-0c2078f0dc6f7b75613b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-0090000000-0c2078f0dc6f7b75613b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-01fee32789401d8776682016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-01fee32789401d8776682016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-0090000000-01fee32789401d8776682016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-df82304fa36d65f6fc452021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-df82304fa36d65f6fc452021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-0090000000-df82304fa36d65f6fc452021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-de7bf88289826d2f61222021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0090000000-821dbeb0f8ad5344f1bb2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004l-0090000000-b32ddb5cfb451de2e44e2021-09-22View Spectrum
Toxicity Profile
Route of ExposureFollowing 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.
Mechanism of ToxicityAlkylating 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.
MetabolismRoute 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: Cisplatin 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.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2A, probably carcinogenic to humans. (31)
Uses/SourcesFor the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentEYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00515
HMDB IDHMDB14656
PubChem Compound ID441203
ChEMBL IDCHEMBL2068237
ChemSpider ID389985
KEGG IDC06911
UniProt IDNot Available
OMIM ID
ChEBI ID27899
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDCPT
ACToR IDNot Available
Wikipedia LinkCisplatin
References
Synthesis Reference

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

MSDSLink
General References
  1. Massart C, Gibassier J, Le Gall F, Raoul ML, Leclech G, Lucas C: [Modulation of cisplatin cytotoxicity by amphotericin B in six human cell lines of medullary thyroid cancer]. Bull Cancer. 1996 Aug;83(8):619-25. [8869041 ]
  2. Garcia-Giralt E, Beuzeboc P, Deffontaines D, Dieras V, Dorval T, Jouve M, Palangie T, Scholl S, Pouillart P: First-line protracted venous infusion fluorouracil with CisDDP or carboplatin in advanced colorectal cancer. J Infus Chemother. 1996 Summer;6(3):149-51. [9229328 ]
  3. Scherini E, Bernocchi G: cisDDP treatment and development of the rat cerebellum. Prog Neurobiol. 1994 Feb;42(2):161-96. [8008824 ]
  4. Van Waardenburg RC, Prins J, Meijer C, Uges DR, De Vries EG, Mulder NH: Effects of c-myc oncogene modulation on drug resistance in human small cell lung carcinoma cell lines. Anticancer Res. 1996 Jul-Aug;16(4A):1963-70. [8712728 ]
  5. Marcucci L, Petrinelli P, Antonelli A, Elli R: Expression of genes carried by pR plasmid in damaged E. coli and mouse cells. Mutat Res. 1994 Aug 1;309(1):53-61. [7519733 ]
  6. Hrubisko M, McGown AT, Fox BW: The role of metallothionein, glutathione, glutathione S-transferases and DNA repair in resistance to platinum drugs in a series of L1210 cell lines made resistant to anticancer platinum agents. Biochem Pharmacol. 1993 Jan 7;45(1):253-6. [8424817 ]
  7. Zhang B, Pan JS, Liu JY, Han SP, Hu G, Wang B: Effects of chemotherapy and/or radiotherapy on survivin expression in ovarian cancer. Methods Find Exp Clin Pharmacol. 2006 Nov;28(9):619-25. [17200728 ]
  8. Kiseleva VI, Vrana O, Brabets I, Poverennyi AM: [Detection of hybridization probes using antibodies to DNA adducts with cis- and trans-diaminodichloroplatinum (II). I. Immunochemical characteristics of DNA modified by cis- and trans-diaminodichloroplatinum (II)]. Mol Biol (Mosk). 1991 Mar-Apr;25(2):503-7. [1881396 ]
  9. He P, Ahn JC, Shin JI, Hwang HJ, Kang JW, Lee SJ, Chung PS: Enhanced apoptotic effect of combined modality of 9-hydroxypheophorbide alpha-mediated photodynamic therapy and carboplatin on AMC-HN-3 human head and neck cancer cells. Oncol Rep. 2009 Feb;21(2):329-34. [19148503 ]
  10. Yamamoto J, Miyagi Y, Kawanishi K, Yamada S, Miyagi Y, Kodama J, Yoshinouchi M, Kudo T: Effect of cisplatin on cell death and DNA crosslinking in rat mammary. Adenocarcinoma in vitro. Acta Med Okayama. 1999 Oct;53(5):201-8. [10561728 ]
  11. Papadopoulou MV, Ji M, Bloomer WD: NLCQ-1, a novel hypoxic cytotoxin: potentiation of melphalan, cisDDP and cyclophosphamide in vivo. Int J Radiat Oncol Biol Phys. 1998 Nov 1;42(4):775-9. [9845094 ]
  12. Fleck C, Kretzschel I, Sperschneider T, Appenroth D: Renal amino acid transport in immature and adult rats during chromate and cisplatinum-induced nephrotoxicity. Amino Acids. 2001;20(2):201-15. [11332454 ]
  13. Osinsky SP, Levitin IY, Bubnovskaya LN, Ganusevich II, Tsikalova MV, Istomin YP, Zhavrid EA, Volpin ME: Modifying effect of organocobalt complexes on the tumour response to anticancer treatments. Anticancer Res. 1997 Sep-Oct;17(5A):3457-62. [9413187 ]
  14. Fukunaga Y, Higashihara A, Nishino Y, Yasunaga T, Jin M, Miyazawa A: Enhanced detection efficiency of genetically encoded tag allows the visualization of monomeric proteins by electron microscopy. J Electron Microsc (Tokyo). 2012 Aug;61(4):229-36. doi: 10.1093/jmicro/dfs043. Epub 2012 Apr 16. [22508950 ]
  15. Necchi D, Scherini E, Bernocchi G: Glial cell reaction to cis-dichlorodiammine platinum treatment in the immature rat cerebellum. Exp Neurol. 1997 Mar;144(1):219-26. [9126174 ]
  16. Morgan RJ Jr, Newman EM, Sowers L, Scanlon K, Harrison J, Akman S, Leong L, Margolin K, Niland J, Raschko J, Somlo G, Carroll M, Chow W, Tetef M, Hamasaki V, Yen Y, Doroshow JH: Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies. Cancer Chemother Pharmacol. 2003 Jun;51(6):459-64. Epub 2003 Apr 15. [12695856 ]
  17. Florio S, Pagnini G, Pagnini U, Crispino A: Effect of cis-diamminedichloroplatinum (II) on rat thymocyte membrane potential. J Chemother. 1996 Apr;8(2):147-53. [8708747 ]
  18. Schweyer S, Soruri A, Heintze A, Radzun HJ, Fayyazi A: The role of reactive oxygen species in cisplatin-induced apoptosis in human malignant testicular germ cell lines. Int J Oncol. 2004 Dec;25(6):1671-6. [15547704 ]
  19. Wilborn F, Brendel M: Formation and stability of interstrand cross-links induced by cis- and trans-diamminedichloroplatinum (II) in the DNA of Saccharomyces cerevisiae strains differing in repair capacity. Curr Genet. 1989 Dec;16(5-6):331-8. [2692851 ]
  20. Kiseleva VI, Turchinskii MF, Poverennyi AM: [II. Use of antibodies to DNA modified by trans-diaminodichloroplatinum, for identification of specific DNA sequences]. Mol Biol (Mosk). 1991 Mar-Apr;25(2):508-14. [1881397 ]
  21. Utsumi H, Kodama S, Tano K, Hashimoto MW, Watanabe H: Establishment and characterization of a hypocatalasemic mouse cell strain. J Radiat Res. 1998 Sep;39(3):165-74. [9868865 ]
  22. Schweyer S, Soruri A, Meschter O, Heintze A, Zschunke F, Miosge N, Thelen P, Schlott T, Radzun HJ, Fayyazi A: Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation. Br J Cancer. 2004 Aug 2;91(3):589-98. [15266324 ]
  23. Bissett D, McLaughlin K, Kelland LR, Brown R: Cisplatin-DNA damage recognition proteins in human tumour extracts. Br J Cancer. 1993 Apr;67(4):742-8. [8471431 ]
  24. Wu YJ, Muldoon LL, Neuwelt EA: The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. J Pharmacol Exp Ther. 2005 Feb;312(2):424-31. Epub 2004 Oct 20. [15496615 ]
  25. Garcia-Giralt E, Omodei Zorini C, Beuzeboc P, Deffontaines D, Dieras V, Dorval T, Jouve M, Palangie T, Scholl S, Pouillart P: First line protracted venous infusion fluorouracil with CisDDP or carboplatine in advanced colorectal cancer. Clin Ter. 1997 Sep;148(9):393-401. [9374077 ]
  26. Chekhun VF, Lukyanova NY, Kovalchuk O, Tryndyak VP, Pogribny IP: Epigenetic profiling of multidrug-resistant human MCF-7 breast adenocarcinoma cells reveals novel hyper- and hypomethylated targets. Mol Cancer Ther. 2007 Mar;6(3):1089-98. [17363502 ]
  27. Gorski MM, Eeken JC, de Jong AW, Klink I, Loos M, Romeijn RJ, van Veen BL, Mullenders LH, Ferro W, Pastink A: The Drosophila melanogaster DNA Ligase IV gene plays a crucial role in the repair of radiation-induced DNA double-strand breaks and acts synergistically with Rad54. Genetics. 2003 Dec;165(4):1929-41. [14704177 ]
  28. Wang P, Gao XF, Bu WY, Zhang J, Hou YF, Niu BH, Wang W, Ma YF, Qi YJ: [Differential proteins in esophageal squamous cell line EC9706/CDDP identified by SILAC quantitative proteomic approach]. Yao Xue Xue Bao. 2012 Mar;47(3):409-16. [22645768 ]
  29. Taki T, Ohnishi T, Arita N, Hiraga S, Hayakawa T: In vivo etoposide-resistant C6 glioma cell line: significance of altered DNA topoisomerase II activity in multi-drug resistance. J Neurooncol. 1998 Jan;36(1):41-53. [9525824 ]
  30. FDA label
  31. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. [17139284 ]
  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. [17016423 ]
  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. 2008 Jan;390(1):37-44. Epub 2007 Oct 12. [17932658 ]
  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 Nov 9;373(5):1123-40. Epub 2007 Aug 23. [17900616 ]
  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. [8640534 ]