Comp-10

Comp-10 is a novel small molecule identified through structure-based screening that functions as a selective allosteric inhibitor of Inosine monophosphate dehydrogenase 2 (IMPDH2). It binds to the GTP allosteric domain of IMPDH2, mimicking the inhibitory action of phosphatidylinositol 3-phosphate (PI(3)P). Unlike existing IMPDH inhibitors such as mycophenolic acid (MPA), Comp-10 potently inhibits human IMPDH2 enzymatic activity (IC50 ~260 nM), selectively reduces IMPDH2 protein levels, and disrupts IMPDH2 filament formation, which MPA tends to stabilize. It has demonstrated significant reduction in cell growth across various hematological malignancy cell lines, including anaplastic large cell lymphoma (ALCL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL), including variants resistant to ALK inhibitors.