A selective DYRK1B inhibitor
AZ191 is a potent and selective DYRK1B inhibitor with IC50 value of 17 nM [1].
DYRK1B (dual-specificity tyrosine phosphorylation-regulated kinase 1B) is particularly expressed in the testis and muscle where it plays an important role in myoblast differentiation. DYRK1B is overexpressed in certain cancers suggesting that it may be an oncogene [1].
In HEK-293 cells, AZ191 at 1uM could't inhibit? DYRK1B autophospho-Tyr273 and selectively inhibited DYRK1B serine/threonine kinase activity. In HEK-293 cells co-expressing CCND1 with either DYRK1A or DYRK1B, AZ191 inhibited phosphorylation of CCND1 with greater potency for DYRK1B over DYRK1A at doses as low as 30–100 nM. AZ191 is a novel DYRK1B-selective inhibitor with ～100-fold selectivity over DYRK2 and 5–10-fold selectivity over DYRK1A. AZ191 will be used as a useful probe for defining DYRK1B functions and DYRK1B substrates [1].
参考文献:
[1]. Ashford AL, Oxley D, Kettle J, 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, 457(1): 43-56.
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