GNF362 (GNF-362) is a highly potent, selective inhibitor of inositol 1,4,5-trisphosphate 3-kinase B (ITPKB) with IC50 of 9 nM.
GNF362 also inhibits Itpka (expressed in the brain, IC50=20 nM) and Itpkc (IC50=19 nM), GNF362 has no activity against a panel of >150 proteins or lipid kinases.
GNF362 ameliorated acute GVHD without impairing GVL against 2 acute myeloid leukemia lines (MLL-AF9-eGFP and C1498-luciferase).
GNF362 more selectively deleted alloreactive T cells without eliminating GVL compared with FK506.
GNF362 attenuated aGVHD lethality in vivo administration.
GNF362 reversed established cGVHD BO and inhibited lung macrophage infiltration, but did not alter GC reactions in both BO and scleroderma models.
GNF362 reversed skin disease in mice with cGVHD and scleroderma.
