SPI-2127

SPI-2127 (also known as SPH2127) is an orally bioavailable small molecule inhibitor of the Menin-MLL (Mixed Lineage Leukemia) protein-protein interaction, developed by Shanghai Pharmaceuticals Holding Co., Ltd. It is specifically designed for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML), particularly those harboring MLL rearrangements (KMT2A-r) or NPM1 mutations. By binding to Menin, SPI-2127 prevents its interaction with MLL fusion proteins, which are critical drivers of leukemogenesis. This disruption leads to the downregulation of pro-leukemogenic transcription factors such as HOXA9 and MEIS1, subsequently inducing cell cycle arrest, differentiation, and apoptosis in leukemia cells.