Anti-tumor activity and mechanism of action for a cyanoaziridine-derivative, AMP423.

ABSTRACT:

Purpose

Preclinical studies evaluated the anti-tumor activity and mechanism of action of AMP423, a naphthyl derivative of 2-cyanoaziridine-1-carboxamide with structural similarity to the pro-oxidant anti-tumor agent imexon.

Methods

The cytotoxic potency was evaluated in vitro against a variety of human cancer cell lines. Mechanism-of-action studies were performed in the human 8226/S myeloma cell line and its imexon-resistant variant, 8226/IM10. In vivo activity was evaluated against human myeloma and lymphoma xenografts in SCID mice. Pharmacokinetics and toxicology were investigated in non-tumor-bearing mice.

Results

The 72-h IC(50)s for all cell types ranged from 2 to 36 μM, across a wide variety of human cancer cell lines. AMP423 was active in SCID mice bearing 8226

SUBMITTER: Dorr RT 

PROVIDER: S-EPMC3314130 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature