Leucettinib-21 (LCTB-21) is a potent, selective DYRKs and CLKs kinases with IC50 of 2.4, 6.7, 12, 33, and 5 nM for DYRK1A, DYRK1B, CLK1, CLK2, and CLK4, respectively.
Leucettinib-21 weakly inhibits DYRK2/3/4, and CLK3 (IC50=200-1000 nM), inhibits only weakly inhibits some kinases (RPS6KA4, CDK7, DMPK) in a panel of 468 kinases at 1 uM.
Leucettinib-21 shows Kd values of 0.272 and 0.388 nM for DYRK1A and CLK1, respectively, 26 and 22 times lower than that for Leucettine L41 (Cat#PC-61025).
Leucettinib-21 triggers a dose-dependent inhibition of endogenous DYRK1A catalytic activity in HT-22 mouse hippocampal neuronal cells with IC50 of 36 nM.
Leucettinib-21 (0-10 uM) inhibits the phosphorylation of reported DYRK1A substrate sites in SH-SY5Y cells, such as Thr286-cyclin D1 and Thr212-Tau, protects cyclin D1 from proteolytic degradation, leading to its accumulation.
Leucettinib-21 (0.4 mg/kg, oral gavage daily, 10 days) corrects memory disorders in the Down syndrome mouse model Ts65Dn, a classical animal model of Down syndrome (DS).