SKI-178

SKI-178 is a novel, small molecule dual-action therapeutic agent designed for the treatment of acute myeloid leukemia (AML). It uniquely co-targets sphingosine kinase 1 (SphK1) and microtubule dynamics. By inhibiting SphK1, SKI-178 disrupts the "sphingolipid rheostat," leading to the accumulation of pro-apoptotic ceramide and depletion of pro-survival sphingosine-1-phosphate (S1P). Simultaneously, it acts as a microtubule-disrupting agent (MDA) by binding to the colchicine site on tubulin. This dual mechanism synergistically induces apoptosis in AML cells, including multi-drug resistant lines, while sparing normal hematopoiesis. Preclinical studies in various mouse models, including patient-derived xenografts, have demonstrated significant therapeutic efficacy and survival extension.