SN-38: A Comprehensive Monograph on a Pivotal Topoisomerase I Inhibitor—From Prodrug Metabolite to Advanced Therapeutic Payload

1.0 Introduction: The Re-emergence of a Potent Camptothecin Analog

The history of oncology is marked by the discovery of natural products with profound cytotoxic activity, whose clinical potential was initially hindered by challenging pharmaceutical properties. Few molecules exemplify this narrative better than SN-38 (7-ethyl-10-hydroxycamptothecin). As a semi-synthetic analog of camptothecin, SN-38 belongs to a class of agents that revolutionized cancer treatment by identifying a novel molecular target: DNA topoisomerase I.[1] However, SN-38 is most widely known not as a drug administered to patients, but as the principal active metabolite of irinotecan (CPT-11), a cornerstone chemotherapeutic agent used in the treatment of various solid tumors, most notably metastatic colorectal cancer.[3] The entire therapeutic rationale for administering the water-soluble prodrug irinotecan is to facilitate the

in vivo generation of SN-38, the molecule responsible for virtually all of the desired antitumor effect.[6]