GNF362 是肌醇三磷酸3'激酶 B (Itpkb) 的选择性，有效且可口服生物利用的抑制剂，IC50为 9 nM。 GNF362 还抑制 Itpka 和 Itpkc，IC50 值分别为 20 nM 和 19 nM。 肌醇三磷酸3'激酶 B (Itpkb) 是一种 Ca2+ 依赖性激酶，其磷酸化 Ins (1,4,5) P3 的 3' 位置，生成肌醇 1,3,4,5-四磷酸 [Ins (1,3,4,5) P4]。
货号:ajcx15616
CAS:1003019-41-7
分子式:C22H21F3N6
分子量：426.44
溶解度:DMSO: 125 mg/mL (293.12 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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].

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]. Animal Model: A Lewis rat antigen-induced arthritis (rAIA) model[1]

[1]. Miller AT, et al. Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19. Sci Immunol. 2019 Oct 25;4(40). pii: eaaw2707.