| Identification | Back Directory | [Name]
Benzamide, N-[3-(5-fluoro-3-pyridinyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-4-(4-methyl-1-piperazinyl)- | [CAS]
2922550-28-3 | [Synonyms]
CLK1-IN-3
Benzamide, N-[3-(5-fluoro-3-pyridinyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-4-(4-methyl-1-piperazinyl)- | [Molecular Formula]
C24H23FN6O | [MOL File]
2922550-28-3.mol | [Molecular Weight]
430.48 |
| Chemical Properties | Back Directory | [density ]
1.345±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
12.27±0.40(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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].
| Animal Model: | Male C57BL/6 mice(8 weeks, injected acetaminophen (HY-66005) (500 mg/kg, ip))[1] | | Dosage: | 10, 20, and 40 mg/kg | | Administration: | IP, once | | Result: | Decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels significantly in dose-dependent. |
| Animal Model: | Male Balb/c mice (aged 8 weeks)[1] | | Dosage: | 10 mg/kg | | Administration: | IV, PO, IP, once (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic Parameters of CLK1-IN-3 in male Balb/C mice[1].
| IV (10 mg/kg) | PO (10 mg/kg) | IP (10 mg/kg) | | Cmax (ng/mL) | 13166.5±875.9 | 1457.4±177.3 | 4654.3±435.3 | | T1/2 (h) | 2.96±1.2 | 5.29±2.1 | 3.27 ±1.1 | | AUC0-t (ng/mL?h) | 9520.5±1011.3 | 1860.2±411.0 | 5010.4±987.2 | | CL (L/h/kg) | 1.05±0.10 | 5.51±1.00 | 3.58±0.82 | | F (%) | | 19.5% | |
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| [IC 50]
CLK1: 5 nM (IC50); CLK2: 42 nM (IC50); CLK4: 108 nM (IC50); DYRK1A: 1521 nM (IC50) | [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. DOI:10.1016/j.ejmech.2023.115168 |
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