CLK1-IN-3 (compound 10ad) is a potent and selective Clk1 inhibitor, with an IC50 of 5 nM and over 300-fold selectivity for Dyrk1A. CLK1-IN-3 also shows a relatively potent inhibition against Clk2 and Clk4, with IC50 values of 42 and 108 nM, respectively. CLK1-IN-3 potently induces autophagy in vitro. CLK1-IN-3 can be used for acute liver injury (ALI) research.
CLK1-IN-3 (compound 10ad) shows potential in anti-tumor because of dual inhibition of Clk1 and Clk2[1].CLK1-IN-3 (10 μM-1000 μM) can effectively bind to Clk1 protein and inhibit its degradation in a dose-dependent manner[1]. CLK1-IN-3 (0-10 μM, 24 h) induces autophagy in Hela, BNLCL.2 and HCT 116 cells[1]. CLK1-IN-3 stimulates the degradation of SQSTM1/p62 (a marker of autolysosomes)[1].
CLK1-IN-3 (compound 10ad) (0-40 mg/kg, IP, once) significantly suppresses acute liver injury (ALI) without apparent liver cell death in the ALI model induced by acetaminophen [1].CLK1-IN-3 (10 mg/kg; IV, PO, IP, once) shows acceptable pharmacokinetic profile, has a relatively long T1/2 with 5.29 h and oral bioavailability of 19.5%[1].
References:
[1]. Yang T, et al. Rational design and appraisal of selective Cdc2-Like kinase 1 (Clk1) inhibitors as novel autophagy inducers for the treatment of acute liver injury (ALI). Eur J Med Chem. 2023 Mar 15;250:115168.