RRC ID 44453
Author Ye L, Ou X, Tian Y, Yu B, Luo Y, Feng B, Lin H, Zhang J, Wu S.
Title Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.
Journal Eur J Med Chem
Abstract Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 μM in TR-FRET-based assay and IC50 value of 5.45 μM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.
Volume 65
Pages 112-8
Published 2013-7-1
DOI 10.1016/j.ejmech.2013.04.004
PII S0223-5234(13)00236-5
PMID 23702473
MeSH Cell Line, Tumor Dose-Response Relationship, Drug Drug Design* Humans Indazoles / chemical synthesis Indazoles / chemistry Indazoles / pharmacology* Models, Molecular Molecular Structure Protein Kinase Inhibitors / chemical synthesis Protein Kinase Inhibitors / chemistry Protein Kinase Inhibitors / pharmacology* Proto-Oncogene Proteins c-met / antagonists & inhibitors* Proto-Oncogene Proteins c-met / metabolism Structure-Activity Relationship
IF 5.573
Times Cited 22
Human and Animal Cells