Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling
Kinases are among the most important families of biomolecules and play an essential role in the regulation of cell proliferation, apoptosis, metabolism, and other critical physiological processes. The dysregulation and gene mutation of kinases are linked to the occurrence and development of various...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/943 |
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| author | Haofan Zhang Fengming He Guiping Gao Sheng Lu Qiaochu Wei Hongyu Hu Zhen Wu Meijuan Fang Xiumin Wang |
| author_facet | Haofan Zhang Fengming He Guiping Gao Sheng Lu Qiaochu Wei Hongyu Hu Zhen Wu Meijuan Fang Xiumin Wang |
| author_sort | Haofan Zhang |
| collection | DOAJ |
| description | Kinases are among the most important families of biomolecules and play an essential role in the regulation of cell proliferation, apoptosis, metabolism, and other critical physiological processes. The dysregulation and gene mutation of kinases are linked to the occurrence and development of various human diseases, especially cancer. As a result, a growing number of small-molecule drugs based on kinase targets are being successfully developed and approved for the treatment of many diseases. The indole/azaindole/oxindole moieties are important key pharmacophores of many bioactive compounds and are generally used as excellent scaffolds for drug discovery in medicinal chemistry. To date, 30 ATP-competitive kinase inhibitors bearing the indole/azaindole/oxindole scaffold have been approved for the treatment of diseases. Herein, we summarize their research and development (R&D) process and describe their binding models to the ATP-binding sites of the target kinases. Moreover, we discuss the significant role of the indole/azaindole/oxindole skeletons in the interaction of their parent drug and target kinases, providing new medicinal chemistry inspiration and ideas for the subsequent development and optimization of kinase inhibitors. |
| first_indexed | 2024-03-11T09:34:50Z |
| format | Article |
| id | doaj.art-e4256cf4c7b144dba5c558e4fa1b9731 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:34:50Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e4256cf4c7b144dba5c558e4fa1b97312023-11-16T17:25:23ZengMDPI AGMolecules1420-30492023-01-0128394310.3390/molecules28030943Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns ProfilingHaofan Zhang0Fengming He1Guiping Gao2Sheng Lu3Qiaochu Wei4Hongyu Hu5Zhen Wu6Meijuan Fang7Xiumin Wang8School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaSchool of Public Health, Xiamen University, Xiamen 361102, ChinaXingzhi College, Zhejiang Normal University, Lanxi 321004, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaKinases are among the most important families of biomolecules and play an essential role in the regulation of cell proliferation, apoptosis, metabolism, and other critical physiological processes. The dysregulation and gene mutation of kinases are linked to the occurrence and development of various human diseases, especially cancer. As a result, a growing number of small-molecule drugs based on kinase targets are being successfully developed and approved for the treatment of many diseases. The indole/azaindole/oxindole moieties are important key pharmacophores of many bioactive compounds and are generally used as excellent scaffolds for drug discovery in medicinal chemistry. To date, 30 ATP-competitive kinase inhibitors bearing the indole/azaindole/oxindole scaffold have been approved for the treatment of diseases. Herein, we summarize their research and development (R&D) process and describe their binding models to the ATP-binding sites of the target kinases. Moreover, we discuss the significant role of the indole/azaindole/oxindole skeletons in the interaction of their parent drug and target kinases, providing new medicinal chemistry inspiration and ideas for the subsequent development and optimization of kinase inhibitors.https://www.mdpi.com/1420-3049/28/3/943indole/azaindole/oxindole derivativesapproved ATP-competitive kinases drugscancerdrug designkinases binding patternsdrug discovery |
| spellingShingle | Haofan Zhang Fengming He Guiping Gao Sheng Lu Qiaochu Wei Hongyu Hu Zhen Wu Meijuan Fang Xiumin Wang Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling Molecules indole/azaindole/oxindole derivatives approved ATP-competitive kinases drugs cancer drug design kinases binding patterns drug discovery |
| title | Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling |
| title_full | Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling |
| title_fullStr | Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling |
| title_full_unstemmed | Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling |
| title_short | Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling |
| title_sort | approved small molecule atp competitive kinases drugs containing indole azaindole oxindole scaffolds r d and binding patterns profiling |
| topic | indole/azaindole/oxindole derivatives approved ATP-competitive kinases drugs cancer drug design kinases binding patterns drug discovery |
| url | https://www.mdpi.com/1420-3049/28/3/943 |
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