Design, Synthesis and Evaluation of Small Molecules as ALK5 Inhibitors

Karpoormath, Rajshekhar/ Noolvi, Malleshappa N./ Patel, Harun M.

ISBN 10: 3659479926 / ISBN 13: 9783659479922

Published by LAP LAMBERT Academic Publishing, 2018

About this Item

52 pages. 8.66x5.91x0.12 inches. In Stock.

Seller Inventory # 3659479926

Bibliographic Details

• Title: Design, Synthesis and Evaluation of Small Molecules as ALK5 Inhibitors
• Publisher: LAP LAMBERT Academic Publishing
• Publication Date: 2018
• Language: English
• ISBN 10: 3659479926
• ISBN 13: 9783659479922
• Binding: Paperback
• Condition: Brand New
• Weight: 0.13 kilograms

About this title

Synopsis

A new series of imidazo[2,1-b][1,3,4]thiadiazoles were synthesized as transforming growth factor-β (TGF- β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β -induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. One of the compound from this series displayed prominent ALK5 inhibition (IC50 = 0.0012 µM) and elective inhibition (91%) against the P38α kinase at 10 µM. The binding mode of this compound by XP docking studies showed that it fits well into the active site cavity of ALK5 by forming broad and tight interactions. Lipinski’s rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use, thereby indicating their potential as a drug-like molecules.