AZ 191

AZ191 is a potent small molecule inhibitor that selectively inhibits DYRK1B with IC50 of 17 nM; selective for DYRK1B over both DYRK1A and DYRK2.IC50 value: 17 nM [1]Target: DYRK1B inhibitorin vitro: Using in vitro kinase assays, phospho-specific immunoblot analysis and MS in conjunction with AZ191 we now show that DYRK1B phosphorylates CCND1 at Thr(286), not Thr(288), in vitro and in cells. In HEK (human embryonic kidney)-293 and PANC-1 cells (which exhibit DYRK1B amplification) DYRK1B drives Thr(286) phosphorylation and proteasome-dependent turnover of CCND1 and this is abolished by AZ191 or DYRK1B RNAi, but not by GSK3β inhibitors or GSK3β RNAi.

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> DYRK

Research Areas >> Cancer

[1]. Ashford AL, et al. A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J. 2014 Jan 1;457(1):43-56.

Harmine | TC-S 7004 | ID 8 | Protein kinase inhibitors 1 | EHT 5372