典型文献
Discovery of small molecule Gαq/11 protein inhibitors against uveal melanoma
文献摘要：
Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies.The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma(UM)cases,making directly targeting Gαq/11 to be a promising strategy for combating UM.Herein,we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors,and iden-tified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties.GQ262 efficiently blocked UM cell proliferation and migration in vitro.Analysis of the apoptosis-related proteins,extracel-lular signal-regulated kinase(ERK),and yes-associated protein(YAP)demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly.Significantly,GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose.Collectively,our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.
文献关键词：
中图分类号：
作者姓名：
Yang Ge;Jun-Jie Deng;Jianzheng Zhu;Lu Liu;Shumin Ouyang;Zhendong Song;Xiaolei Zhang;Xiao-Feng Xiong
作者机构：
National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation,Guangdong Province Engineering Laboratory for Druggability and New Drugs Evaluation,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China
文献出处：
引用格式：
[1]Yang Ge;Jun-Jie Deng;Jianzheng Zhu;Lu Liu;Shumin Ouyang;Zhendong Song;Xiaolei Zhang;Xiao-Feng Xiong-.Discovery of small molecule Gαq/11 protein inhibitors against uveal melanoma)[J].药学学报（英文版）,2022(08):3326-3340
A类：
Constitutively,imidazopiperazine,GQ262
B类：
Discovery,small,molecule,inhibitors,against,uveal,melanoma,activated,proteins,caused,by,specific,mutations,mediate,development,multiple,malignancies,mutated,are,perceived,oncogenic,drivers,vast,majority,UM,cases,making,directly,targeting,be,promising,strategy,combating,Herein,report,optimization,derivatives,iden,tified,improved,inhibitory,activity,drug,like,properties,efficiently,blocked,proliferation,migration,vitro,Analysis,apoptosis,related,extracel,lular,signal,regulated,kinase,ERK,yes,associated,YAP,demonstrated,that,distinctly,induced,cells,disrupted,downstream,effectors,Significantly,showed,outstanding,antitumor,efficacy,vivo,good,safety,testing,dose,Collectively,our,findings,along,favorable,pharmacokinetics,revealed,may
AB值：
0.629832
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机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
