9-Aminocamptothecin

9-Aminocamptothecin (9-Amino-CPT) is a topoisomerase I inhibitor with potent anticancer activity^[1]. IC50 & Target:Topoisomerase^[1] In Vitro: In human breast (MCF-7), bladder (MGH-U1), and colon (HT-29) cancer cell lines, 9-Aminocamptothecin cytotoxicity increases with both higher drug concentrations and longer exposure times. Minimal cell killing is also observed unless 9-Aminocamptothecin concentrations exceeds a threshold of 2.7 nm^[1]. 9-Aminocamptothecin inhibits PC-3, PC-3M, DU145, and LNCaP cells with IC₅₀ values of 34.1, 10, 6.5, and 8.9 nM, respectively after 96 h of drug exposure^[2]. In Vivo: 9-Aminocamptothecin (9-Amino-CPT) inhibits tumor growth at the lowest oral dose (0.35 mg/kg/day), whereas higher oral doses (0.75 and 1 mg/kg/day) and s.c. administration (4 mg/kg/week) causes tumor regression. 9-Aminocamptothecin is well tolerated at all doses, with no toxic death or weight loss of more than 10% observed in any group^[2]. 9-Aminocamptothecin induces complete remissions in 55 % of SCID mice engrafted with human myeloid leukemia. The oral and intravenous routes are equally effective. The results with this pre-clinical model support the evaluation of 9-Aminocamptothecin as antileukemic agent in a phase I trial in patients with AML^[3].