AI Article Synopsis
- A series of imidazole and pyrazole compounds were synthesized and tested for their ability to inhibit the ALK5 enzyme.
- The most effective compound, pyrazole derivative 21b, demonstrated an IC50 value of 0.018 μM and achieved 95% inhibition in a luciferase reporter assay.
- Docking analysis indicated that 21b fits perfectly into the ATP binding site of ALK5, forming multiple hydrogen bonds, and also showed a high selectivity index against p38α MAP kinase.
Article Abstract
A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 μM and showed 95% inhibition at 0.03 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38α MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions.
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| http://dx.doi.org/10.1016/j.bmc.2014.03.022 | DOI Listing |
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