Camptothecin and taxol: discovery to clinic

Abstract

Camptothecin (CPT) is a pentacyclic alkaloid isolated from wood and bark of Camptotheca acuminata. Initially it was found to be highly active in a number of mouse in vivo cancer assays. Subsequently, CPT was found to uniquely inhibit an enzyme, topoisomerase I, which is involved in DNA replication. A number of CPT analogs are in advanced clinical trial, and two, Topotecan and CPT-11, have been approved for marketing by the FDA. taxol, a taxane alkaloid, was isolated from Taxus brevifolia. Taxol is a highly cytotoxic compound active in several mouse antitumor 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.