Cisplatin (CAS: 15663-27-1)

Cl₂H₆N₂Pt

• Potent platinum-based antineoplastic agent [1, 10].
• Anticancer compound [1]. Forms inter- and intrastrand DNA adducts/crosslinks, consequently blocking DNA replication and transcription and inducing cell death [2, 12, 13, 15].
• Nephrotoxic when used in vivo [3].
• Potent chemoimmunotherapeutic. Stimulates the immune responses by activating macrophages and other cells of the immune system [4, 6].
• Apoptosis inducer via p53-dependent and -independent mechanisms [5, 7, 8].
• Induces apoptosis through caspase-3 activation and XIAP expression inhibition [9, 14].
• Targets other proteins and enzymes [10].
• Non-competitive NHE-1 inhibitor, an archetypal, membrane-bound mechanosensitive sodium-hydrogen ion transporter [16].

1. Antitumor action of cis-dichlorobis(methylamine)platinum(II): G.R. Gale, et al.; J. Natl. Cancer Inst. 51, 1227 (1973)
2. Preliminary characterization of the adducts formed between the antitumor compounds cis-Pt(NH3)2Cl2 and DNA: N.P. Johnson; BBRC 104, 1394 (1982)
3. Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity: A.B. Campbell, et al.; Cancer Treat. Rep. 67, 169 (1983)
4. Immune response of mice exposed to cis-diamminedichloroplatinum: O. Bagasra, et al.; Cancer Immunol. Immunother. 19, 142 (1985)
5. Cisplatin induces a persistent activation of JNK that is related to cell death: I. Sanchez-Perez, et al.; Oncogene 16, 533 (1998)
6. Antigen presentation by cisplatin-activated macrophages: role of soluble factor(s) and second messengers: R.A. Singh & A. Sodhi; Immunol. Cell Biol. 76, 513 (1998)
7. Cisplatin-induced apoptosis in human proximal tubular epithelial cells is associated with the activation of the Fas/Fas ligand system: M.S. Razzaque, et al.; Histochem. Cell Biol. 111, 359 (1999)
8. The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage: J.G. Gong, et al.; Nature 399, 806 (1999)
9. Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma: K. Seki, et al.; Cancer Chemother. Pharmacol. 45, 199 (2000)
10. What is the "best" platinum: cisplatin, carboplatin, or oxaliplatin? J. Lokich; Cancer Invest. 19, 756 (2001)
11. Biomolecular targets for platinum antitumor drugs: R.N. Bose; Mini Rev. Med. Chem. 2, 103 (2002)
12. Cisplatin: mode of cytotoxic action and molecular basis of resistance: Z.H. Siddik; Oncogene 22, 7265 (2003)
13. New clues for platinum antitumor chemistry: Kinetically controlled metal binding to DNA: J. Reedijk; PNAS 100, 3611 (2003)
14. Cisplatin inhibits the expression of X-linked inhibitor of apoptosis protein in human LNCaP cells: T. Nomura, et al.; Urol. Oncol. 22, 453 (2004)
15. Inhibition of transcription by platinum antitumor compounds: R.C. Todd & S.J. Lippard; Metallomics 1, 280 (2009)
16. Nongenomic effects of cisplatin: acute inhibition of mechanosensitive transporters and channels without actin remodeling: N. Milosavljevic, et al.; Cancer Res. 70, 7514 (2010)