Cisplatin
[CAS# 15663-27-1]

Identification

• Classification: API >> Antineoplastic agents >> Other antineoplastic agents
• Name: Cisplatin
• Synonyms: cis-Diaminedichloroplatinum(II)
• Molecular Formula: Cl₂H₆N₂Pt
• Molecular Weight: 300.05
• CAS Registry Number: 15663-27-1
• EC Number: 239-733-8
• SMILES: [NH2-].[NH2-].Cl[Pt+2]Cl

Properties

• Melting point: 270 °C (Expl.)
• Boiling point: (Decomposes) °C (Expl.)
• Solubility: DMSO 83 mg/mL, <0.1 g/100 mL at 19 °C (Expl.)

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Risk Statements: H300-H316-H319-H360-H362-H370-H372-H340-H350
• Safety Statements: P501-P263-P260-P270-P202-P201-P264-P280-P337+P313-P305+P351+P338-P308+P311-P332+P313-P301+P310+P330-P405

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Carcinogenicity	Carc.	1B	H350
Serious eye damage	Eye Dam.	1	H318
Eye irritation	Eye Irrit.	2	H319
Respiratory sensitization	Resp. Sens.	1	H334
Skin sensitization	Skin Sens.	1	H317
Reproductive toxicity	Repr.	1B	H360
Germ cell mutagenicity	Muta.	1B	H340
Specific target organ toxicity - single exposure	STOT SE	3	H335
Carcinogenicity	Carc.	1A	H350
Germ cell mutagenicity	Muta.	1A	H340
Carcinogenicity	Carc.	2	H351
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315
Reproductive toxicity	Lact.	-	H362
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Specific target organ toxicity - single exposure	STOT SE	1	H370
Skin corrosion	Skin Corr.	1	H314
Eye irritation	Eye Irrit.	2A	H318
Skin sensitization	Skin Sens.	1B	H317
Respiratory sensitization	Resp. Sens.	1A	H334
Acute toxicity	Acute Tox.	1	H310
Skin sensitization	Skin Sens.	1A	H317
Acute toxicity	Acute Tox.	2	H310
Respiratory sensitization	Resp. Sens.	1B	H334
Reproductive toxicity	Repr.	1A	H360

• Transport Information: UN 1851; UN 3288

Discovery and Applications

Cisplatin, also known as cis-diamminedichloroplatinum(II), is a chemotherapy drug widely used in the treatment of various cancers, including testicular, ovarian, bladder, and lung cancers. It is a platinum-containing compound that works by interfering with the DNA in cancer cells, preventing them from replicating and ultimately leading to cell death.

Cisplatin was discovered in 1845 by the chemist Michele Peyrone, although its anticancer properties were not recognized until much later. The compound was first studied in the 1960s by researchers Barnett Rosenberg and his colleagues at Michigan State University. They discovered that platinum-based compounds, particularly cisplatin, had significant anticancer activity. Their findings were groundbreaking, as cisplatin demonstrated a potent ability to inhibit the growth of cancer cells in laboratory experiments, leading to its development as an effective cancer treatment.

The mechanism of action of cisplatin is primarily based on its ability to form covalent bonds with the DNA in cancer cells. The platinum ion at the center of the cisplatin molecule binds to the purine bases of DNA, specifically guanine, leading to the formation of DNA adducts. These adducts cause DNA cross-links, which prevent the DNA strands from separating and replicating. This disruption in DNA replication activates cellular repair mechanisms, which are often overwhelmed, leading to cell death. The ability of cisplatin to target rapidly dividing cancer cells makes it particularly effective in treating tumors.

Cisplatin is administered intravenously and is typically given in cycles, often in combination with other chemotherapy agents to enhance its therapeutic effect. Despite its efficacy in treating various cancers, cisplatin is associated with several side effects, the most notable of which include nephrotoxicity (kidney damage), ototoxicity (hearing loss), and myelosuppression (bone marrow suppression). These side effects can limit the dosage and frequency of cisplatin administration, necessitating careful monitoring of patients receiving the drug.

Over the years, the clinical use of cisplatin has led to the development of several related platinum-based drugs, such as carboplatin and oxaliplatin. These drugs have been designed to improve upon cisplatin by reducing its side effects or enhancing its efficacy against certain types of cancer. However, cisplatin remains one of the most widely used and well-established chemotherapy drugs in clinical practice.

In addition to its use in cancer treatment, cisplatin has also been studied for its potential use in other medical applications, such as treating infections and exploring its role in the treatment of other diseases, although its primary role remains as an anticancer agent.

In conclusion, cisplatin is a cornerstone in cancer chemotherapy, with a well-established history of effectiveness in treating a variety of cancers. Its discovery and subsequent use in medicine have significantly advanced cancer treatment, although its side effects continue to present challenges for patients undergoing therapy. Ongoing research aims to mitigate these side effects and improve the drug's efficacy, ensuring that cisplatin remains an important tool in the fight against cancer.

References

1994. Expression of glutathione-S-transferases alpha and pi in gastric cancer: a correlation with cisplatin resistance. Cancer Chemotherapy and Pharmacology, 34(1).
DOI: 10.1007/bf00685078

1998. Bone marrow metastasis in astrocytic gliomata. Journal of Neuro-Oncology, 37(1).
DOI: 10.1023/a:1005909127196

2003. NMR studies of the relationship between the changes of membrane lipids and the cisplatin-resistance of A549/DDP cells. Cancer Cell International, 3.
DOI: 10.1186/1475-2867-3-5