homocamptothecin

Homocamptothecin (hCPT) is a semi-synthetic derivative of the natural alkaloid camptothecin, characterized by the expansion of the six-membered alpha-hydroxylactone E-ring into a seven-membered beta-hydroxylactone ring. This structural modification significantly enhances the stability of the lactone form in human plasma, which is critical for its biological activity. Like its parent compound, homocamptothecin acts as a potent inhibitor of DNA topoisomerase I, stabilizing the covalent complex between the enzyme and DNA, leading to double-strand breaks and apoptosis during the S-phase of the cell cycle. Several derivatives, such as elomotecan (BN80927) and diflomotecan, have entered clinical trials for the treatment of various solid tumors, including pancreatic, lung, and colon cancers. It is also being explored as a payload for antibody-drug conjugates (ADCs) and as a radiosensitizing agent.

Other names

hCPT20-homocamptothecin