Uses
A potent JAK3 inhibitor; selective for JAK3 over JAK1, JAK2 and TYK2. It also inhibits GSK-3β, PKCα and PKCθ.
Biological Activity
tcs 21311 is a potent and selective jak3 inhibitor with the ic50 values of 8 nm. tcs 21311 shows high selectivity for jak3 over jak1, jak2 and tyk2. the ic50 values are 1017, 2550 and 8055 nm respectively. tcs 21311 exihibits inhibitory effect on gsk-3β, pkcα and pkcθ with the ic50 values of 3, 13 and 68 nm, respectively [1].janus kinases (jak) belong to a small family of cytoplasmic protein tyrosine kinases including jak1, jak2, tyk2, and jak3, which play important roles in initiating the cytokine-triggered signaling events by activators of transcription (stat) proteins via tyrosine phosphorylation [2]. due to its association with relevant cytokine signaling pathways, jak3 serves as an important target for therapeutic intervention in the treatment of inflammatory diseases, autoimmune disorders and organ transplant rejection [2].
IC 50
JAK3: 8 nM (IC50); JAK2: 2.55 μM (IC50); JAK1: 1.017 μM (IC50); PKCα: 13 nM (IC50); PKCθ: 68 nM (IC50); GSK-3β: 3 nM (IC50)
References
[1] thoma g, nuninger f, falchetto r, et al. identification of a potent janus kinase 3 inhibitor with high selectivity within the janus kinase family[j]. journal of medicinal chemistry, 2010, 54(1): 284-288.
[2] clark m p, george k m, bookland r g, et al. development of new pyrrolopyrimidine-based inhibitors of janus kinase 3 (jak3)[j]. bioorganic & medicinal chemistry letters, 2007, 17(5): 1250-1253.
