2. Academic Validation
  3. 4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase

4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase

  • Bioorg Med Chem. 2014 May 1;22(9):2724-32. doi: 10.1016/j.bmc.2014.03.022.
Cheng Hua Jin 1,  Maddeboina Krishnaiah 1,  Domalapally Sreenu 1,  Vura Bala Subrahmanyam 1,  Hyun-Ju Park 2,  So-Jung Park 2,  Yhun Yhong Sheen 1,  Dae-Kee Kim 3
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Republic of Korea.
  • 2 School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
  • 3 Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Republic of Korea. Electronic address: dkkim@ewha.ac.kr.
PMID: 24704197 DOI: 10.1016/j.bmc.2014.03.022
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.

Keywords

ALK5 inhibitor; Cancer; Cell-based luciferase reporter assay; Docking; Fibrosis; Kinase assay; TGF-β.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z