Centanamycin (ML-970; indolecarboxamide)

Chemical name: N-[4-Amino-1-(2-chloroethyl)-2-naphthyl]-5,6,7-trimethoxy-1H-indole-2-carboxamide

Centanamycin, also known as  ML-970, AS-I-145 and NSC 716970, is an indolecarboxamide synthesized as a less toxic analog of CC-1065 and duocarmycin, a natural product that binds the A-T-rich DNA minor groove and alkylates DNA.

The compound, an analog of CC-1065 (a DNA minor-groove binding agent) is under preclinical investigation as a novel anticancer agent. Centanamycin has potent in vitro and in vivo cytotoxic activity, with an average GI(50) of 34 nM.  Studies have shown that centanamycin is relatively stable in plasma, being largely intact after an 8-h incubation in mouse plasma at 37°C. The compound was extensively bound to plasma proteins.

Centanamycin is only minimally metabolized by the enzymes present in S9 preparation and is not appreciably excreted in the urine or feces.   In research studies the solution formulation provided higher C(max), AUC, F values, and greater bioavailability, although the suspension formulation resulted in a later T(max) and a slightly longer T(1/2).

See: ADC Review / Knowledge Center

[1] Rayburn E, Wang W, Li M, Zhang X, Xu H, Li H, Qin JJ, Jia L, Covey J, Lee M, Zhang R. Preclinical pharmacology of novel indolecarboxamide ML-970, an investigative anticancer agent. Cancer Chemother Pharmacol. 2012 Jun;69(6):1423-31. doi: 10.1007/s00280-012-1851-9. Epub 2012 Feb 25.
[2] Rayburn E, Wang W, Grau S, Li H, Xu H, Zhang X, Li M, Sommers C, Jia L, Lee M, Zhang R. Abstract 3605: Enterohepatic circulation of indolecarboxamide ML-970 (NSC 716970), an investigative anticancer agent. Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Published in Cancer Res April 15, 2010 70; 3605

Last Editorial Review: March 16, 2015