Your browser doesn't support javascript.
loading
Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
Wang, Zhen; Bian, Huan; Bartual, Sergio G; Du, Wenting; Luo, Jinfeng; Zhao, Hu; Zhang, Shasha; Mo, Cheng; Zhou, Yang; Xu, Yong; Tu, Zhengchao; Ren, Xiaomei; Lu, Xiaoyun; Brekken, Rolf A; Yao, Libo; Bullock, Alex N; Su, Jin; Ding, Ke.
Afiliação
  • Wang Z; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Bian H; University of the Chinese Academy of Sciences , 19 Yuquan Road, Beijing 100049, China.
  • Bartual SG; Department of Biochemistry and Molecular Biology, The Fourth Military Medical University , 17 Changle Western Road, Xi'an, Shaanxi 710032, P. R. China.
  • Du W; Structural Genomics Consortium, University of Oxford , Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.
  • Luo J; Division of Surgical Oncology, Department of Surgery and the Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center , Dallas Texas 75390-8593, United States.
  • Zhao H; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Zhang S; Department of Biochemistry and Molecular Biology, The Fourth Military Medical University , 17 Changle Western Road, Xi'an, Shaanxi 710032, P. R. China.
  • Mo C; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Zhou Y; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Xu Y; University of the Chinese Academy of Sciences , 19 Yuquan Road, Beijing 100049, China.
  • Tu Z; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Ren X; University of the Chinese Academy of Sciences , 19 Yuquan Road, Beijing 100049, China.
  • Lu X; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Brekken RA; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Yao L; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Bullock AN; State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • Su J; School of Pharmacy, Jinan University , 601 Huangpu Avenue West, Guangzhou 510632, China.
  • Ding K; Division of Surgical Oncology, Department of Surgery and the Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center , Dallas Texas 75390-8593, United States.
J Med Chem ; 59(12): 5911-6, 2016 06 23.
Article em En | MEDLINE | ID: mdl-27219676
ABSTRACT
The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose Pulmonar / Desenho de Fármacos / Inibidores de Proteínas Quinases / Receptor com Domínio Discoidina 1 / Isoquinolinas Limite: Animals Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose Pulmonar / Desenho de Fármacos / Inibidores de Proteínas Quinases / Receptor com Domínio Discoidina 1 / Isoquinolinas Limite: Animals Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: China