ASN-3186

ASN-3186 is a novel, potent, and selective small molecule inhibitor of ubiquitin specific peptidase 1 (USP1), an enzyme involved in DNA damage response and repair. It demonstrates single-digit nanomolar IC50 for USP1 with over 1000-fold selectivity against other deubiquitinating enzymes. ASN-3186 has shown strong anti-proliferative activity in preclinical models of BRCA1/2-mutant and homologous recombination-deficient (HRD+) cancers, including triple-negative breast cancer. In vivo studies indicate higher potency than comparator agents such as KSQ4279, likely due to superior oral bioavailability. The drug acts through a synthetic lethality mechanism by inhibiting DNA repair pathways critical for tumor cell survival in HRD+ settings. ASN-3186 is being developed primarily for advanced solid tumors—including breast cancer and ovarian cancer—both as monotherapy and in combination with PARP inhibitors or gemcitabine[1][3][8].