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Clinical data
Trade names Platinol, others
Synonyms Cisplatinum, platamin,
neoplatin, cismaplat, cis-
diamminedichloridoplatinum(II)
(CDDP)
AHFS/Drugs.com Monograph
MedlinePlus a684036
Pregnancy AU: D
category
US: D (Evidence of risk)
Routes of Intravenous
administration
ATC code L01XA01 (WHO )
Legal status
Legal status AU: S4 (Prescription
only)
CA: ℞-only
UK: POM (Prescription
only)
US: ℞-only
Pharmacokinetic data
Bioavailability 100% (IV)
Protein binding > 95%
Elimination half-life 30–100 hours
Excretion Renal
Identifiers
IUPAC name
(SP-4-2)-diamminedichloroplatinum(II)
ChemSpider 76401
UNII Q20Q21Q62J
KEGG D00275
ChEBI CHEBI:27899
ChEMBL ChEMBL2068237
SMILES
[NH3+]-[Pt-2](Cl)(Cl)[NH3+]
InChI
InChI=1S/2ClH.2H3N.Pt/h2*1H;2*1H3;/q;;;;+2/p-2
Key:LXZZYRPGZAFOLE-UHFFFAOYSA-L
(what is this?) (verify)
Medical use
Cisplatin is administered intravenously as
short-term infusion in normal saline for
treatment of solid and haematological
malignancies. It is used to treat various
types of cancers, including sarcomas,
some carcinomas (e.g., small cell lung
cancer, squamous cell carcinoma of the
head and neck and ovarian cancer),
lymphomas, bladder cancer, cervical
cancer,[7] and germ cell tumors.
Pharmacology
Cisplatin interferes with DNA replication,
which kills the fastest proliferating cells,
which in theory are cancerous. Following
administration, one chloride ion is slowly
displaced by water to give the aquo
complex cis-[PtCl(NH3)2(H2O)]+, in a
process termed aquation. Dissociation of
the chloride is favored inside the cell
because the intracellular chloride
concentration is only 3–20% of the
approximately 100 mM chloride
concentration in the extracellular
fluid.[12][13]
Cisplatin resistance
Cisplatin combination chemotherapy is the
cornerstone of treatment of many cancers.
Initial platinum responsiveness is high but
the majority of cancer patients will
eventually relapse with cisplatin-resistant
disease. Many mechanisms of cisplatin
resistance have been proposed including
changes in cellular uptake and efflux of the
drug, increased detoxification of the drug,
inhibition of apoptosis and increased DNA
repair.[16] Oxaliplatin is active in highly
cisplatin-resistant cancer cells in the
laboratory; however, there is little evidence
for its activity in the clinical treatment of
patients with cisplatin-resistant cancer.[16]
The drug paclitaxel may be useful in the
treatment of cisplatin-resistant cancer; the
mechanism for this activity is unknown.[17]
Transplatin
Molecular structure
History
The compound cis-[Pt(NH3)2Cl2] was first
described by Michele Peyrone in 1845, and
known for a long time as Peyrone's salt.[23]
The structure was deduced by Alfred
Werner in 1893.[14] In 1965, Barnett
Rosenberg, Van Camp et al. of Michigan
State University discovered that
electrolysis of platinum electrodes
generated a soluble platinum complex
which inhibited binary fission in
Escherichia coli (E. coli) bacteria. Although
bacterial cell growth continued, cell
division was arrested, the bacteria growing
as filaments up to 300 times their normal
length.[24] The octahedral Pt(IV) complex
cis-[PtCl4(NH3)2], but not the trans isomer,
was found to be effective at forcing
filamentous growth of E. coli cells. The
square planar Pt(II) complex, cis-
[PtCl2(NH3)2] turned out to be even more
effective at forcing filamentous
growth.[25][26] This finding led to the
observation that cis-[PtCl2(NH3)2] was
indeed highly effective at regressing the
mass of sarcomas in rats.[27] Confirmation
of this discovery, and extension of testing
to other tumour cell lines launched the
medicinal applications of cisplatin.
Cisplatin was approved for use in
testicular and ovarian cancers by the U.S.
Food and Drug Administration on 19
December 1978.,[14][28][29] and in the UK
(and in several other European countries)
in 1979.[30]
Synthesis
The synthesis of cisplatin starts from
potassium tetrachloroplatinate.[31][32] The
tetraiodide is formed by reaction with an
excess of potassium iodide. Reaction with
ammonia forms K2[PtI2(NH3)2] which is
isolated as a yellow compound. When
silver nitrate in water is added insoluble
silver iodide precipitates and
K2[Pt(OH2)2(NH3)2] remains in solution.
Addition of potassium chloride will form
the final product which precipitates [31] In
the triiodo intermediate the addition of the
second ammonia ligand is governed by the
trans effect.[31]
See also
Carboplatin
Dicycloplatin
References
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"Cellular processing of platinum anticancer
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13. Johnstone, Timothy C.; Suntharalingam,
Kogularamanan; Lippard, Stephen J. (2016).
"The Next Generation of Platinum Drugs:
Targeted Pt(II) Agents, Nanoparticle
Delivery, and Pt(IV) Prodrugs" . Chem. Rev.
116 (5): 3436–3486.
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15. Pruefer, Franz G.; Lizarraga, F.;
Maldonado, V.; Melendez-Zajgla, Jorge
(June 2008). "Participation of Omi HtrA2
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18. Coluccia, Mauro; Natile, Giovanni
(January 2007). "Trans-platinum complexes
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ISSN 1871-5206 . PMID 17266508 .
19. Miessler, Gary L.; Tarr, Donald A. (1999).
Inorganic Chemistry (2nd ed.). Prentice
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20. Housecroft, Catherine E.; Sharpe, Alan
G. (2005). Inorganic Chemistry (2nd ed.).
Pearson Prentice Hall. p. 689. ISBN 978-0-
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21. Housecroft, Catherine E.; Sharpe, Alan
G. (2005). Inorganic Chemistry (2nd ed.).
Pearson Prentice Hall. p. 550. ISBN 978-0-
130-39913-7.
22. Miessler, Gary L.; Tarr, Donald A. (1999).
Inorganic Chemistry (2nd ed.). Prentice
Hall. p. 284. ISBN 978-0-13-841891-5.
23. Peyrone, M. (1844). "Ueber die
Einwirkung des Ammoniaks auf
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(1): 1–29. doi:10.1002/jlac.18440510102 .
24. Rosenberg, B.; Vancamp, L.; Krigas, T.
(1965). "Inhibition of cell division in
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25. Rosenberg, B.; Van Camp, L.; Grimley, E.
B.; Thomson, A. J. (March 1967). "The
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26. Thomson, A. J. (2007). Christie, D. A.;
Tansey, E. M., eds. The Discovery, Use and
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27. Rosenberg, B.; Van Camp, L.; Trosko, J.
E.; Mansour, V. H. (April 1969). "Platinum
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Further reading
Riddell, Imogen A.; Lippard, Stephen J.
(2018). "Cisplatin and Oxaliplatin: Our
Current Understanding of Their Actions". In
Sigel, Astrid; Sigel, Helmut; Freisinger, Eva;
Sigel, Roland K. O. Metallo-Drugs:
Development and Action of Anticancer
Agents. Metal Ions in Life Sciences. 18.
Berlin: de Gruyter GmbH. pp. 1–42.
doi:10.1515/9783110470734-007 .
ISBN 978-3-11-046984-4.
PMID 29394020 .
External links
Cisplatin: The Invention of an Anticancer
Drug by Andri Smith
Anti-cancer Agents: A treatment of
Cisplatin and their analogues by Sia M.
Liu (excellent detailed overview)
MedlinePlus page on cisplatin
IARC Monograph: "Cisplatin"
Retrieved from
"https://en.wikipedia.org/w/index.php?
title=Cisplatin&oldid=889076810"