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 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].
Animal Model:
A Lewis rat antigen-induced arthritis (rAIA) model[1]
Dosage:
6 or 20 mg/kg
Administration:
Orally administration; 6 or 20 mg/kg; twice daily; 21 days
Result:
Reduced knee swelling in both the 20mg/kg and 6mg/kg treatment groups of GNF362 by 47% and 34%, respectively.
storage
Store at -20°C
References
[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. DOI:10.1371/journal.pone.0131071
