Biological Activity |
GNF362 is a selective, potent, and orally bioavailable inhibitor of inositol trisphosphate 3' kinase B (Itpkb) with an IC50 of 9 nM. GNF362 also inhibits Itpka and Itpkc with IC50 values of 20 nM and 19 nM, respectively. Inositol trisphosphate 3' kinase B (Itpkb) is a Ca2+-dependent kinase, which phosphorylates the 3' position of Ins (1, 4, 5) P3 to generate inositol 1, 3, 4, 5-tetrakisphosphate [Ins (1, 3, 4, 5) P4][1]. In Vitro: GNF362 (0-10 mM) blocks Ins (1, 3, 4, 5) P4 production, enhances antigen receptor-driven Ca2+ responses and lead to apoptosis of activated T cells in an Itpkb-dependent manner in lymphocytes[1]. GNF362 augments SOC responses following antigen receptor cross-linking, with an EC50 of 12 nM in primary B or T lymphocytes[1]. In Vivo: GNF362 (orally administration; 6 or 20 mg/kg; twice daily; 21 days) shows minimal block in antibody production but shows significant inhibition of joint swelling at 6 mg/kg, reduces inflammatory cell infiltrate, joint damage, and proteoglycan loss at 20 mg/kg[1]. |