AMXI-5001, a novel dual parp1/2 and microtubule polymerization inhibitor for the treatment of human cancers.

ABSTRACT: Poly (ADP-ribose) polymerase (PARP) has recently emerged as a central mediator in cancer resistance against numerous anticancer agents to include chemotherapeutic agents such as microtubule targeting agents and DNA damaging agents. Here, we describe AMXI-5001, a novel, highly potent dual PARP1/2 and microtubule polymerization inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. The potency and selectivity of AMXI-5001 were determined by biochemical assays. Anticancer activity either as a single-agent or in combination with other antitumor agents was evaluated in vitro. In vivo antitumor activity as a single-agent was assessed in a triple-negative breast cancer (TNBC) model. AMXI-5001 demonstrates comparable IC50 inhibition against PARP and mic

SUBMITTER: Lemjabbar-Alaoui H 

PROVIDER: S-EPMC7471353 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature