CLK1-IN-3

• CAT Number: I041227
• CAS Number: 2922550-28-3
• Molecular Formula: C24H23FN6O
• Molecular Weight: 430.48
• Purity: ≥95%
• Synonyms: N-[3-(5-fluoropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-4-(4-methylpiperazin-1-yl)benzamide
• InChI: InChI=1S/C24H23FN6O/c1-30-6-8-31(9-7-30)20-4-2-16(3-5-20)24(32)29-19-11-21-22(15-28-23(21)27-14-19)17-10-18(25)13-26-12-17/h2-5,10-15H,6-9H2,1H3,(H,27,28)(H,29,32)
• InChIKey: LQKHTRXKHPHEPP-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=CC4=C(NC=C4C5=CC(=CN=C5)F)N=C3

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[1].
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 (HY-66005, APAP)[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].

Reference

[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.
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