Irinotecan hydrochloride is an inhibitor of Topoisomerase I, and is is activated by hydrolysis to SN-38 (the active metabolite of Irinotecan).
Irinotecan hydrochloride is the hydrochloride salt of a semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death.
Increasing concentrations of Irinotecan (0.1, 1, 10, 100, and 1000 μg/mL) inhibits the growth of all cell lines in a dose-dependent manner. COLO-357 cells are most sensitive and HT29 most resistant to Irinotecan in the MTT assay on incubation for 90 min. The IC50 concentrations are 100, 50, 5.4, 23 and 46 μg/mL Irinotecan for HT29, NMG 64/84, COLO-357, MIA PaCa-2 and PANC-1, respectively