Development of PI3Kγ selective inhibitors: the strategies and application
文献类型：期刊论文
| 作者 | Gu, Dong-Yan2; Zhang, Meng-Meng1; Li, Jia1 ; Zhou, Yu-Bo1; Sheng, Rong2
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2023-10-06 |
| 页码 | 10 |
| 关键词 | PI3K PI3K gamma inhibitors isoform selectivity drug development rational drug design |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-023-01166-8 |
| 通讯作者 | Sheng, Rong(shengr@zju.edu.cn) |
| 英文摘要 | The gamma isoform of Class I PI3Ks (PI3K gamma) is primarily found in leukocytes and is essential for the function of myeloid cells, as it regulates the migration, differentiation, and activation of myeloid-lineage immune cells. Thus, PI3K gamma has been identified as a promising drug target for the treatment of inflammation, autoimmune disease, and immuno-oncology. Due to the high incidence of serious adverse events (AEs) associated with PI3K inhibitors, in the development of PI3K gamma inhibitors, isoform selectivity was deemed crucial. In this review, an overview of the development of PI3K gamma selective inhibitors in the past years is provided. The isoform selectivity of related drugs was achieved by different strategies, including inducing a specificity pocket by a propeller-shape structure, targeting steric differences in the solvent channel, and modulating the conformation of the Asp-Phe-Gly DFG motif, which have been demonstrated feasible by several successful cases. The insights in this manuscript may provide a potential direction for rational drug design and accelerate the discovery of PI3K gamma selective inhibitors. |
| WOS关键词 | PI3K INHIBITORS ; SOLID TUMORS ; INFLAMMATION ; DISCOVERY ; PI3K-DELTA ; TARGETS ; THERAPY ; LESSONS ; PATHWAY |
| 资助项目 | National Natural Science Foundation of China[82003780] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001081779500001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307406]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Sheng, Rong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gu, Dong-Yan,Zhang, Meng-Meng,Li, Jia,et al. Development of PI3Kγ selective inhibitors: the strategies and application[J]. ACTA PHARMACOLOGICA SINICA,2023:10. |
| APA | Gu, Dong-Yan,Zhang, Meng-Meng,Li, Jia,Zhou, Yu-Bo,&Sheng, Rong.(2023).Development of PI3Kγ selective inhibitors: the strategies and application.ACTA PHARMACOLOGICA SINICA,10. |
| MLA | Gu, Dong-Yan,et al."Development of PI3Kγ selective inhibitors: the strategies and application".ACTA PHARMACOLOGICA SINICA (2023):10. |
入库方式： OAI收割
来源：上海药物研究所
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