ASP9853

ASP9853 is an orally bioavailable small molecule inhibitor of inducible nitric oxide synthase (iNOS) dimerization, resulting in decreased nitric oxide (NO) production. It was developed by Astellas Pharma as a potential antineoplastic agent, with the hypothesis that reducing NO levels could enhance the efficacy of taxane-based chemotherapy such as docetaxel and paclitaxel. Preclinical studies showed that ASP9853 combined with taxanes inhibited tumor growth more effectively than taxanes alone in non-small cell lung cancer xenografts. However, a Phase 1 clinical trial in patients with advanced solid tumors found that the combination led to unacceptable toxicity (notably neutropenia), and did not achieve predicted efficacious concentrations. The study was terminated early due to toxicity and lack of clear efficacy[1][2][3][5][7].