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].