SC0245

SC0245 is a novel, orally administered small molecule inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase, a key regulator in the DNA damage response pathway. By inhibiting ATR, SC0245 disrupts the cellular response to replication stress and DNA damage, leading to increased cancer cell death—particularly in tumors deficient in ATM pathway or ARID1A. Preclinical studies have shown that SC0245 has potent anti-proliferative activity against various human cancers and demonstrates marked antitumor efficacy in animal models of gastric and colorectal cancer with ATM pathway or ARID1A deficiency. The drug exhibits high selectivity for ATR/ATRIP complexes (IC50 14–43 nM), favorable pharmacokinetics with oral bioavailability over 80% across species, and synergistic effects when combined with topoisomerase I inhibitors such as irinotecan. SC0245 is currently being evaluated in phase Ib/II clinical trials for advanced solid malignancies—including extensive-stage small cell lung cancer (ES-SCLC)—as monotherapy or in combination with irinotecan[1][2][6].