Karenitecin

Karenitecin (Cositecan) is a topoisomerase I inhibitor, with potent anti-cancer activity.

In Vitro

Karenitecin is a topoisomerase I inhibitor, with potent anti-cancer activity. Karenitecin inhibits cell growth of A253 cells with IC 10 , IC 50 , and IC 90 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. Karenitecin inhibits several human colon cancer cell lines such as COLO205, COLO320, LS174T, SW1398 and WiDr cells, with IC 50 s of 2.4 nM, 1.5 nM, 1.6 nM, 2.9 nM, and 3.2 nM, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal administration

Mice The human tumor xenografts grown in nude mice are measured twice a week in 3 dimensions with vernier calipers. The volume is calculated by the equation length × width × thickness × 0.5, and expressed in mm 3 . At the start of treatment (designated as day 0), groups of 5 to 6 tumor-bearing mice are formed to provide a mean tumor volume of approximately 150 mm 3 in each group. Doses of Karenitecin and CPT-11 for the daily × 5 schedule are administered according to the maximum tolerated dose (MTD) for tumor-bearing mice. This maximum tolerated dose is based on the occurrence of a mean weight loss of approximately 10% of the initial weight within the first 2 weeks after the start of the treatment. Recovery of the weight loss should be completed on day 14; consequently, mice are weighed on weekdays for 2 weeks and, thereafter, twice a week. The MTD is assessed in groups of 3 non-tumor-bearing nude mice per dose level . aladdin has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:Topoisomerase I