This potent and selective DYRK inhibitor (FW = 429.53 g/mol), also systematically named N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4- (1-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine, selectively targets DYRK1B, a Dual specificity tyrosine-phosphorylation-regulated kinase, with an IC50 value of 17 nM, or about 5x and 110x higher affinity than for DYRK1A and DYRK2. AZ191 is effective both in vitro and in cells. DYRK1B has also been proposed to promote the turnover of Cyclin D1, a key regulator of mammalian G1-S-phase transitions. Cyclin D1 is phosphorylated on Thr-286 by GSK3β (or glycogen synthase kinase 3β), thereby promoting its degradation.
