Unknown

Dataset Information

0

Design and Optimization of 3'-(Imidazo[1,2-a]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as Selective DDR1 Inhibitors.

ABSTRACT: DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3'-(imidazo[1,2-a]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound 8v potently inhibited DDR1 with an IC50 of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC50 = 1740 nM) and negligible activities against Bcr-Abl (IC50 > 10 ?M) and c-Kit (IC50 > 10 ?M). 8v also exhibited excellent selectivity in a KINOMEscan screening platform with 468 kinases. This compound dose-dependently suppressed NSCLC cell tumorigenicity, migration, and invasion. Collectively, these studies support its potential application for treatment of NSCLC.

SUBMITTER: Mo C 

PROVIDER: S-EPMC7074218 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Design and Optimization of 3'-(Imidazo[1,2-<i>a</i>]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as Selective DDR1 Inhibitors.

Mo Cheng C   Zhang Zhang Z   Li Yupeng Y   Huang Minhao M   Zou Jian J   Luo Jinfeng J   Tu Zheng-Chao ZC   Xu Yong Y   Ren Xiaomei X   Ding Ke K   Lu Xiaoyun X  

ACS medicinal chemistry letters 20200106 3

DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3'-(imidazo[1,2-<i>a</i>]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound <b>8v</b> potently inhibited DDR1 with an IC<sub>50</sub> of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC<sub>50</sub> = 1740 nM) and negligib  ...[more]

Similar Datasets

Unknown N-tert-Butyl-2-[4-(dimethyl-amino)-phen-yl]imidazo[1,2-a]pyrazin-3-amine.
| S-EPMC3629650 | biostudies-literature
Unknown N-tert-Butyl-2-(2,6-di-chloro-phen-yl)imidazo[1,2-a]pyrazin-3-amine.
| S-EPMC3685091 | biostudies-literature
Unknown 1-(4-Meth-oxy-phen-yl)ethane-1,2-diyl 1,1'-biphenyl-2,2'-dicarboxyl-ate.
| S-EPMC3379233 | biostudies-literature
Unknown 1-Phenylethane-1,2-diyl 1,1'-biphenyl-2,2'-dicarboxylate.
| S-EPMC3344650 | biostudies-literature
Unknown 1-(2-Bromophenyl)ethane-1,2-diyl 1,1'-biphenyl-2,2'-dicarboxylate.
| S-EPMC3344651 | biostudies-literature
Unknown 2-(3-Chloro-1,2-dihydro-pyrazin-2-yl-idene)malononitrile.
| S-EPMC2968665 | biostudies-literature
Unknown N-[2-(3-Methyl-1-oxo-1,2-dihydro-pyrrolo-[1,2-a]pyrazin-2-yl)eth-yl]methane-sulfonamide.
| S-EPMC3007363 | biostudies-literature
Unknown Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
| S-EPMC5053573 | biostudies-literature
Unknown 6-[(4'-Ethoxycarbonyl-[1,1'-biphenyl]-4-yl)oxy]hexanoic acid.
| S-EPMC3790444 | biostudies-literature
Unknown New Transmission-Selective Antimalarial Agents through Hit-to-Lead Optimization of 2-([1,1'-Biphenyl]-4-carboxamido)benzoic Acid Derivatives.
| S-EPMC10946866 | biostudies-literature