Please note: Any medical or genetic information present in this entry is not intended as a diagnosis of your problem, but rather is provided as a helpful guide for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Information is not necessarily complete. Please see your doctor for diagnosis and treatment.

Please note: DNAtraffic database is the project under construction and information on this page is not finished yet.

Cisplatin


ACCESSION NB: DB00515 (APRD00359)


TYPE: small molecule


GROUP: approved


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.

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antineoplastic Agents Radiation-Sensitizing Agents Cross-Linking Reagents

ABSORPTION: Not Available

INDICATION:
For the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.

PHARMACODYNAMICS:
Cisplatin 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 ACTION:
Alkylating 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.

PROTEIN BINDING:
Greater than 90%.

METABOLISM:
Cisplatin is a widely used chemotherapeutic agent. It reacts with nucleophilic bases in DNA and forms 1,2-d(ApG), 1,2-d(GpG) and 1,3-d(GpTpG) intrastrand crosslinks, interstrand crosslinks and monofunctional adducts. The presence of these adducts in DNA is through to be responsible for the therapeutic efficacy of cisplatin. The exact signal transduction pathway that leads to cell cycle arrest and cell death following treatment with the drug is not known but cell death is believed to be mediated by the recognition of the adducts by cellular proteins.

TOXICITY:
Not Available

AFECTED ORGANISMS:
Humans and other mammals