ARC-111

ARC-111 (Topovale) is a synthetic small molecule and non-camptothecin inhibitor of topoisomerase I (TOP1). Developed by Advantek Biopharm, it was designed to overcome resistance mechanisms common to camptothecin derivatives, such as efflux by the breast cancer resistance protein (BCRP) transporter. ARC-111 stabilizes the covalent TOP1-DNA cleavage complex, leading to DNA double-strand breaks and subsequent apoptosis. Furthermore, it has been shown to inhibit the accumulation of hypoxia-inducible factor-1alpha (HIF-1α) under hypoxic conditions, which may enhance its antitumor activity in poorly oxygenated tumor regions. Preclinical studies demonstrated efficacy in colon cancer and Wilms' tumor models, and the drug has been investigated in Phase 1 clinical trials for advanced solid tumors.

Brand names

Topovale

Other names

8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one