Structure-based design of tetrahydroisoquinoline-7-carboxamides as selective discoidin domain receptor 1 (DDR1) inhibitors.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2016
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| _version_ | 1826272120912478208 |
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| author | Wang, Z Bian, H Bartual, S Du, W Luo, J Zhao, H Zhang, S Mo, C Zhou, Y Xu, Y Tu, Z Ren, X Lu, X Brekken, R Yao, L Bullock, A Su, J Ding, K |
| author_facet | Wang, Z Bian, H Bartual, S Du, W Luo, J Zhao, H Zhang, S Mo, C Zhou, Y Xu, Y Tu, Z Ren, X Lu, X Brekken, R Yao, L Bullock, A Su, J Ding, K |
| author_sort | Wang, Z |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:07:32Z |
| format | Journal article |
| id | oxford-uuid:50a9ec00-791b-4a2e-a3af-7e614f122a56 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:07:32Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:50a9ec00-791b-4a2e-a3af-7e614f122a562022-03-26T16:14:56ZStructure-based design of tetrahydroisoquinoline-7-carboxamides as selective discoidin domain receptor 1 (DDR1) inhibitors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:50a9ec00-791b-4a2e-a3af-7e614f122a56EnglishSymplectic Elements at OxfordAmerican Chemical Society2016Wang, ZBian, HBartual, SDu, WLuo, JZhao, HZhang, SMo, CZhou, YXu, YTu, ZRen, XLu, XBrekken, RYao, LBullock, ASu, JDing, KThe 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. |
| spellingShingle | Wang, Z Bian, H Bartual, S Du, W Luo, J Zhao, H Zhang, S Mo, C Zhou, Y Xu, Y Tu, Z Ren, X Lu, X Brekken, R Yao, L Bullock, A Su, J Ding, K 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 |
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