Karenitecin (Cositecan) is a topoisomerase I inhibitor, with potent anti-cancer activity. IC50 & Target: Topoisomerase I^[1] In Vitro: Karenitecin is a topoisomerase I inhibitor, with potent anti-cancer activity. Karenitecin inhibits cell growth of A253 cells with IC₁₀, IC₅₀, and IC₉₀ values of 0.01, 0.07, and 0.7 μM after 2 h treatment. Karenitecin induces DNA damage (0.01, 0.07, and 0.7 μM), and increases cyclin E and cdk2 protein expression in A253 cells (0.07, and 0.7 μM). Karenitecin markedly enhances the cyclin B/cdc2-associated kinase activity at low concentration, but slightly suppresses this kinase activity at higher concentration^[1]. Karenitecin inhibits several human colon cancer cell lines such as COLO205, COLO320, LS174T, SW1398 and WiDr cells, with IC₅₀s of 2.4 nM, 1.5 nM, 1.6 nM, 2.9 nM, and 3.2 nM, respectively^[2]. In Vivo: Karenitecin shows maximum growth inhibition of 61% on COLO320 cells and 54% on COLO205 colon cancer cells via i.p. administration of 1 mg/kg in mice. Karenitecin (1.0 mg/kg daily × 5 i.p.) significantly suppresses growth inhibition both in the parental Pgp-negative xenografts and in the Pgp-positive xenografts^[2].