HBI-2375

HBI-2375 is a first-in-class, selective small molecule inhibitor targeting the interaction between MLL1 (Mixed Lineage Leukemia 1, also known as KMT2A) and WDR5 (WD Repeat Domain 5), which is critical for MLL1 histone methyltransferase activity. By inhibiting this protein-protein interaction, HBI-2375 disrupts the regulation of downstream genes involved in the progression of leukemias and solid tumors. Preclinical studies have demonstrated that HBI-2375 inhibits MLL1-WDR5 activity both in vitro and in animal models, showing efficacy against various cancers including leukemia, glioblastoma, glioma, lung cancer, colorectal cancer, and other solid tumors. Notably, it can cross the blood-brain barrier—suggesting potential utility for primary or metastatic brain lesions—and has shown synergistic effects when combined with anti-PD1 checkpoint inhibitors by modulating immune cell activity within the tumor microenvironment[1][2][3][4][5].