HMPL-506

HMPL-506 is a novel, investigational, highly potent and selective small molecule inhibitor designed for oral administration that targets the menin protein. Menin acts as a scaffold protein regulating gene expression and cell signaling. Disruption of the menin–MLL (mixed-lineage leukemia, also known as KMT2A) interaction is considered a promising therapeutic strategy in acute leukemias with MLL rearrangements (MLL-r) or nucleophosmin 1 (NPM1) mutations—genetic alterations that play key roles in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Preclinical studies show HMPL-506 strongly inhibits menin–MLL interaction and demonstrates potent anti-tumor activity against both MLL-r and NPM1-mutant tumor models. It has shown synergistic effects when combined with other agents such as BCL2 inhibitors, FLT3 inhibitors, azacytidine, or CDK4/6 inhibitors. The drug displays favorable pharmacokinetics, high selectivity for its target, low risk of cardiac toxicity, and acceptable safety properties. Currently in Phase I clinical trials in China for hematological malignancies including AML, ALL, multiple myeloma (MM), and other genetically defined leukemias[1][2][3][4][5][6].