Saul Schepartz, Ph.D.
Former Deputy Director, DCTD

Camptothecin itself went into clinical trial very early, a very active compound in the L1210 system. Unfortunately because we didn't really have a good idea of the pharmacology of that drug and because of its very poor solubility we ended up using a sodium salt to make it soluble. Unfortunately that decreased its clinical activity and increased its toxicity.

The net result being that camptothecin was dropped. But later observations showing that camptothecin and its analogs had a very unusual mechanism of action; namely inhibition of topoisomerase 1, generated interest in analogs, and two analogs have since actually reached the market in 1996, topotecan and irinotecan. So one could say that it took 30 years or so for the initial observation of camptothecin's activity for a drug to get on the market.