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Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors
[Image: see text] 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 K(d) value of 4.7 nM and suppresses its kinase activity with an IC(50) value of 9.4 nM, but it is sign...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2016
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053573/ https://www.ncbi.nlm.nih.gov/pubmed/27219676 http://dx.doi.org/10.1021/acs.jmedchem.6b00140 |
| _version_ | 1782458439756152832 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Wang, Zhen |
| collection | PubMed |
| description | [Image: see text] 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 K(d) value of 4.7 nM and suppresses its kinase activity with an IC(50) 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. |
| format | Online Article Text |
| id | pubmed-5053573 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2016 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-50535732016-10-10 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 J Med Chem [Image: see text] 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 K(d) value of 4.7 nM and suppresses its kinase activity with an IC(50) 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. American Chemical Society 2016-05-24 2016-06-23 /pmc/articles/PMC5053573/ /pubmed/27219676 http://dx.doi.org/10.1021/acs.jmedchem.6b00140 Text en Copyright © 2016 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
| spellingShingle | 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 Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors |
| title | Structure-Based
Design of Tetrahydroisoquinoline-7-carboxamides
as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors |
| title_full | Structure-Based
Design of Tetrahydroisoquinoline-7-carboxamides
as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors |
| title_fullStr | Structure-Based
Design of Tetrahydroisoquinoline-7-carboxamides
as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors |
| title_full_unstemmed | Structure-Based
Design of Tetrahydroisoquinoline-7-carboxamides
as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors |
| title_short | Structure-Based
Design of Tetrahydroisoquinoline-7-carboxamides
as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors |
| title_sort | structure-based
design of tetrahydroisoquinoline-7-carboxamides
as selective discoidin domain receptor 1 (ddr1) inhibitors |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053573/ https://www.ncbi.nlm.nih.gov/pubmed/27219676 http://dx.doi.org/10.1021/acs.jmedchem.6b00140 |
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