Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3.

Tian LU; Yong LI; Wenchao LU; Twgm Spitters; Xueyu Fang; Jun Wang; Simian Cai; Jing Gao; Yanting Zhou; Zhe Duan; Huan Xiong; Liping Liu; Qi LI; Hualiang Jiang; Kaixian Chen; Hu Zhou; Hua Lin; Huijin Feng; Bing Zhou; Christopher L Antos; Cheng Luo

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Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3.

Author: Tian LU ¹ ; Yong LI ² ; Wenchao LU ³ ; Twgm SPITTERS ⁴ ; Xueyu FANG ⁴ ; Jun WANG ⁵ ; Simian CAI ⁴ ; Jing GAO ⁶ ; Yanting ZHOU ⁶ ; Zhe DUAN ² ; Huan XIONG ⁷ ; Liping LIU ² ; Qi LI ² ; Hualiang JIANG ² ; Kaixian CHEN ¹ ; Hu ZHOU ⁶ ; Hua LIN ² ; Huijin FENG ⁸ ; Bing ZHOU ⁸ ; Christopher L ANTOS ⁴ ; Cheng LUO ¹
Author Information

1. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
2. The Center for Chemical Biology, Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
3. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
4. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
5. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
6. Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
7. Pharmacological and Toxicological Chemistry and Biochemistry Laboratory, UMR 8601 CNRS, University of Paris, Paris Cedex 06, 75270, France.
8. Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Publication Type:Journal Article
Keywords: ABPP, activity-based protein profiling; Covalent inhibitor; HCC, hepatocellular carcinoma.; Hippo pathway; MS, mass spectrometry; Palmitoylation inhibitor.; TAZ, transcriptional co-activator with PDZ-binding motif; TEAD, TEA domain family; TEAD3; TEAD3, TEA domain transcription factor 3; YAP, Yes-associated protein
From: Acta Pharmaceutica Sinica B 2021;11(10):3206-3219
CountryChina
Language:English
Abstract: The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC