期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 243, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114684
关键词
TEAD; YAP; Palmitoylation; Protein-protein interaction; Covalent inhibitor
资金
- National Natural Science Foundation of China [82073682, 81872724]
- Jinan Innovation Team Project [2021GXRC069]
- Science and Technology Commission of Shanghai Municipality [22ZR1474500, 18431907100]
TEADs play important roles in the Hippo pathway and their dysregulation can lead to various diseases. Several inhibitors and activators of TEADs have been identified, but further development is needed for clinical applications.
TEADs are transcription factors and core downstream components of the Hippo pathway. Mutations of the Hippo pathway and/or dysregulation of YAP/TAZ culminate in aberrant transcriptional activities of TEADs, which were considered as key contributing factors of mesotheliomas, fibrotic diseases, Alzheimer's diseases, Huntington's diseases, suppressive immune response, and drug resistance, among others. To modulate transcriptional activities of TEADs, several pharmacological approaches have been pursued, including TEAD/YAP protein-protein inter-action inhibitors, TEAD PBP inhibitors, and TEAD activators. As summarized in this review, a large number of inhibitors and activators of TEADs have been reported with decent in vitro potencies, a few exerted robust and compelling in vivo efficacies, and three that are undergoing clinical trials for the treatment of human cancers. Despite clinical advancement of the TEAD PBP inhibitors, development of other types TEAD inhibitors and ac-tivators generally lags behind. Information showcased herein might benefit discovery of next generation TEAD modulators for treatment of human oncological diseases and beyond.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据