ISM3091

ISM3091 is a highly selective, orally bioavailable small molecule inhibitor of ubiquitin specific peptidase 1 (USP1), developed using Insilico Medicine’s artificial intelligence drug discovery platform. It acts by inhibiting USP1, a key regulator in the DNA damage response and repair pathway. By blocking USP1 activity, ISM3091 disrupts the deubiquitination of FANCI-FANCD2 complexes and impairs DNA repair mechanisms—particularly relevant in tumors with BRCA mutations or homologous recombination deficiencies. This synthetic lethality approach positions ISM3091 as a next-generation targeted therapy for advanced solid tumors. Preclinical studies have shown potent anti-proliferative effects in BRCA-mutant tumor cells and robust anti-tumor activity both as monotherapy and in combination with PARP inhibitors such as olaparib. The drug was discovered by Insilico Medicine using its AI-driven Chemistry42 platform and has been out-licensed to Exelixis for global development and commercialization[2][3][4][5][6][7][8][10].

Other names

XL309XL-309XL 309