ISM3412

ISM3412 is a novel, orally available small molecule inhibitor of methionine adenosyltransferase 2A (MAT2A), developed by Insilico Medicine using artificial intelligence-driven drug discovery platforms. It is designed to selectively target cancers with homozygous methylthioadenosine phosphorylase (MTAP) deletion, which accounts for approximately 15% of all cancers. Preclinical studies have demonstrated that ISM3412 has favorable drug-like properties, including good solubility and permeability, low molecular weight, low plasma protein binding, high oral bioavailability, and a favorable safety profile. In animal models and cancer cell lines with natural MTAP deficiency—including pancreatic cancer, bladder cancer, and non-small cell lung cancer—ISM3412 showed strong anti-tumor efficacy at low doses. The compound can be used as monotherapy or in combination with chemotherapy agents or PRMT5 inhibitors to achieve synergistic effects. ISM3412 is currently being evaluated in Phase 1 clinical trials for patients with locally advanced or metastatic solid tumors harboring MTAP deletions[1][3][4][5][6].