Spiromustine: a new agent entering clinical trials.
Spiromustine is a new alkylating agent, of interest since it was rationally designed as a lipophilic compound capable of penetrating the CNS. This lipophilicity may also enhance alkylating activity against tumors other than brain tumors. Preclinical screening has shown activity against a variety of tumors, including an intracranially implanted ependymoblastoma. Alkylating activity has been demonstrated in an intracerebral glioma in the rat. Spiromustine is a cell cycle non-specific agent. Animal pharmacology studies have shown a biphasic plasma decay curve, with hepatic metabolism and excretion, an enterohepatic circulation of metabolites, and approximately 50% renal excretion of unchanged drug. Toxicology studies in mice, rats and dogs showed that dose-related myelosuppression, and neurotoxicity predominated; other organ toxicities were mild. Spiromustine is currently entering Phase I clinical trials on a variety of schedules.
D000477:Alkylating Agents; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D006827:Hydantoins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009588:Nitrogen Mustard Compounds / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D006827:Hydantoins; D009588:Nitrogen Mustard Compounds; C015511:spiromustine