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Structure-based discovery of potent inhibitors of Axl: design, synthesis, and biological evaluation.
Wu, Shuang; Liao, Min; Li, Minxiong; Sun, Mingming; Xi, Ning; Zeng, Youlin.
Afiliação
  • Wu S; Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University Changsha 410081 PR China youlinzengcn@gmail.com.
  • Liao M; Ningbo University School of Medicine 818 Fenghua Road Ningbo Zhejiang 315211 China xining@nbu.edu.cn.
  • Li M; Sunshine Lake Pharmaceutical Co. Ltd Dongyangguang Hi-tech Park Dongguan Guangdong 523871 China.
  • Sun M; Sunshine Lake Pharmaceutical Co. Ltd Dongyangguang Hi-tech Park Dongguan Guangdong 523871 China.
  • Xi N; School of Chemistry & Chemical Engineering, Guangxi University Nanning 530004 China.
  • Zeng Y; Sunshine Lake Pharmaceutical Co. Ltd Dongyangguang Hi-tech Park Dongguan Guangdong 523871 China.
RSC Med Chem ; 13(10): 1246-1264, 2022 Oct 19.
Article em En | MEDLINE | ID: mdl-36325401
Commonly overexpressed in many cancers and associated with tumor growth, metastasis, drug resistance, and poor overall survival, Axl has emerged as a promising target for cancer therapy. However, the availability of new chemical forms for Axl inhibition is limited. Herein, we present the development and characterization of novel Axl inhibitors, including the design, synthesis, and structure-activity relationships (SARs) of a series of diphenylpyrimidine-diamine derivatives. Most of these compounds exhibited remarkable activity against the Axl kinase. In particular, the promising compound m16 showed the highest enzymatic inhibitory potency (IC50 = 5 nM) and blocked multiple tumor cells' proliferation potencies (the CC50 of 4 out of 42 cancer cell lines <100 nM). Furthermore, compound m16 also possessed preferable pharmacokinetic profiles and liver microsome stability. All these favorable results make m16 a good leading therapeutic candidate for further development.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article