CLK1-IN-1

CLK1-IN-1 is a potent and selective of Cdc2-like kinase 1 (CLK1) inhibitor, with an IC₅₀ of 2 nM. IC50 & Target: IC50: 2 nM (CLK1)^[1]. In Vitro: CLK1 is the most potently inhibited kinase (IC₅₀: 2 nM). In addition to CLK1, only two kinases have an IC₅₀ value less than 100 nM, namely CLK2 (IC₅₀: 31 nM) and CLK4 (IC₅₀: 8 nM), DYRK1A is the strongest off-target. The ability of CLK1-IN-1 to induce autophagy in BNL CL.2 and SKOV-3 (human ovarian cancer cell line) cells is also examined. The effects of CLK1-IN-1 on yellow LC3 puncta also displays obvious dose dependency, and a dose of 10 μM shows the best performance. In addition, in CLK1-IN-1-treated cells, the number of red LC3 puncta (mRFP signals only35) increases compared with that of DMSO-treated cells, indicating the formation of autolysosomes. Importantly, CLK1-IN-1 stimulats the degradation of SQSTM1/p62 and increases the ratio of red LC3 puncta to yellow LC3 puncta, both of which indicate an induction of autophagic flux by CLK1-IN-1^[1]. In Vivo: APAP exposure results in severe liver injury, and treatment with CLK1-IN-1 (ip, 30 mg/kg) imparts a significant hepatoprotective effect. The results show that treatment with CLK1-IN-1 decreases serum ALT and AST levels significantly such that both marker enzymes return to normal levels^[1].