7-Ethyl-10-hydroxycamptothecin (SN-38)

SN-38 (7-Ethyl-10-hydroxycamptothecin) is a potent antineoplastic agent and the primary active metabolite of the prodrug irinotecan. It belongs to the camptothecin class of compounds and exerts its cytotoxic effects by specifically targeting and inhibiting DNA topoisomerase I, an enzyme essential for relieving torsional strain during DNA replication and transcription. By stabilizing the DNA-topoisomerase I cleavable complex, SN-38 causes irreversible DNA damage and triggers programmed cell death in rapidly dividing cancer cells. While highly effective against various solid tumors, including colorectal and lung cancers, its clinical use as a standalone agent is limited by poor water solubility and significant toxicities such as severe diarrhea and neutropenia. Consequently, it is primarily utilized as the active component of prodrugs or as a payload in antibody-drug conjugates like sacituzumab govitecan.

Other names

SN387-ethyl-10-hydroxy-camptothecinActive metabolite of irinotecanNK012

SN-38 binds to and stabilizes the covalent ternary complex formed between DNA and the enzyme topoisomerase I. This stabilization prevents the re-ligation of single-strand DNA breaks, leading to the formation of lethal double-strand DNA breaks when the replication fork encounters the stalled complex during the S phase of the cell cycle, ultimately triggering programmed cell death.