Spiromustine: a new agent entering clinical trials

D. Dale Shoemaker, Peter J. O'Dwyer, Silvia Marsoni, Jacqueline Plowman, J. Paul Davignon, Ruth D. Davis

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)303-308
Number of pages6
JournalInvestigational New Drugs
Volume1
Issue number4
DOIs
Publication statusPublished - Dec 1983

Keywords

  • blood-brain barrier
  • spirohydantoin mustard
  • spiromustine

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

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