CAMPTOTHECIN AND TAXOL - DISCOVERY TO CLINIC

Camptothecin (CPT) is a pentacyclic alkaloid isolated from wood and ba rk of Camptotheca acuminata. Initially it was found to be highly activ e in a number of mouse in vivo cancer assays. Subsequently, CPT was fo und to uniquely inhibit an enzyme, topoisomerase I, which is involved in DNA replication. A number of CPT analogs are in advanced clinical t rial, and two, Topotecan and CPT-11, have been approved for marketing by the FDA. taxol, a taxane alkaloid, was isolated from Taxus brevifol ia. Taxol is a highly cytotoxic compound active in several mouse antit umor assays. It was subsequently found to uniquely inhibit tubulin, a protein involved in mitosis. After clinical evaluation, it has become the drug of choice for treatment of ovarian cancer. (C) 1998 John Wile y & Sons. Inc.