SNDX-50469 + GT19715

SNDX-50469 + GT19715 is a combination therapy pairing the menin inhibitor SNDX-50469, which disrupts menin-MLL interactions to suppress HOX gene expression and induce differentiation in AML cells with MLL rearrangements (MLL-r) or mutant NPM1 (mtNPM1), with the molecular glue GT19715, a dual degrader targeting GSPT1 (a translation termination factor) and c-Myc (a proto-oncogene driving proliferation). Developed through preclinical studies combining Syndax Pharmaceuticals' SNDX-50469 and Kintor Pharma's GT19715, this pairing shows synergistic cell death in AML cell lines (e.g., MOLM-13, MV4;11, OCI-AML2) and patient-derived cells harboring MLL-r, mtNPM1, or FLT3 mutations, independent of TP53 status, with enhanced efficacy against leukemia stem/progenitor cells via complementary downregulation of survival proteins like BCL2, CDK6, and MYC-driven pathways.[5][1]