Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.
Eur J Med Chem, 2013/7;65:112-8.
Ye L[1], Ou X, Tian Y, Yu B, Luo Y, Feng B, Lin H, Zhang J, Wu S
Affiliations
PMID: 23702473
Impact factor: 7.088
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.
Keywords: AQKULDWMVLPKPM-RQNOJGIXSA-N; ASSDAYRAIJUAKP-UHFFFAOYSA-N; Bioisosterism principles; IOEGMAJBPLCGLZ-RQNOJGIXSA-N; Indazole; Isomer; KFHKXMBLOGYCPH-OGESRWMOSA-N; KUZAYSZLNQTGIG-UHFFFAOYSA-N; LNULRIFOOHDLKU-UHFFFAOYSA-N; Molecular docking; QONCLFMRNBSJDL-UHFFFAOYSA-N; SGCGRBMTXZLJBR-OGESRWMOSA-N; Suzuki coupling reaction; VMWYPUTZWINMTO-UHFFFAOYSA-N; VXDNOGKPNKBTFZ-UHFFFAOYSA-N; c-Met inhibitor
MeSH terms
Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Design; Humans; Indazoles; Models, Molecular; Molecular Structure; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Structure-Activity Relationship
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