HM97662

HM97662 is an oral, highly potent next-generation small molecule inhibitor that targets both Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2), the enzymatic core subunits of the polycomb repressive complex 2 (PRC2). By dual inhibition of EZH1 and EZH2, HM97662 blocks PRC2-mediated methylation of histone H3 at lysine 27 (H3K27me3), leading to transcriptional reactivation of tumor suppressor genes. This mechanism is designed to overcome resistance seen with selective EZH2 inhibitors and enhance antitumor efficacy. Preclinical studies have demonstrated that HM97662 exhibits strong growth inhibitory effects in a variety of cancer cell lines—including those with ARID1A mutations—and shows activity against tazemetostat-resistant cells with elevated EZH1. It has shown potent antitumor activity in xenograft models for both hematological malignancies (such as B-cell lymphoma, T-cell lymphoma, multiple myeloma) and solid tumors (including ovarian and bladder cancers). The drug also has potential to restore anticancer immunity in cancers with LKB1 loss. Currently, a phase 1 clinical trial is ongoing for patients with advanced or metastatic solid tumors[1][2][6][7].