DiamminedichloroplatinumII

Diamminedichloroplatinum(II), commonly called cisplatin, is a platinum-based anticancer drug used in chemotherapy. Its chemical formula is PtCl2(NH3)2, and it adopts a square-planar geometry with two ammine (NH3) ligands cis to each other and two chloride ligands. In physiological conditions, the chlorides are readily displaced by water to form active aqua species capable of binding DNA.

The drug forms covalent adducts with DNA, primarily 1,2-intrastrand crosslinks between adjacent guanine bases, which distort the double helix and block replication and transcription, triggering apoptosis. Protein interactions and oxidative stress also contribute to cytotoxic effects. Resistance can arise via reduced drug uptake, increased efflux, enhanced DNA repair, or thiol-based detoxification.

Clinical use: Cisplatin was discovered in 1965 by Barnett Rosenberg and colleagues and approved for medical use in the 1970s. It is used to treat several cancers, notably testicular cancer, and also ovarian, bladder, head and neck, cervical, and lung cancers, often in combination regimens. Administration is intravenous, typically with hydration and antiemetic prophylaxis to manage nephrotoxicity and nausea.

Adverse effects and safety: Nephrotoxicity is the principal dose-limiting toxicity; neurotoxicity and ototoxicity can occur; nausea and vomiting are common. Dose planning includes renal function assessment and aggressive IV hydration; protective agents, such as amifostine, may be used in some settings.

Related compounds: Cisplatin is the prototype; its platinum(II) neighbors include carboplatin and oxaliplatin, which share mechanism but differ in toxicity and spectrum of activity. The trans isomer of dichloro-bis(ammine) platinum(II) lacks comparable anticancer activity.