Affordable Access

deepdyve-link
Publisher Website

Fluorescence polarization assay for the identification and evaluation of inhibitors at YAP-TEAD protein-protein interface 3.

Authors
  • Zhou, Wei1
  • Li, Yiping2
  • Song, Jinhua3
  • Li, Chenglong4
  • 1 Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, 32610, United States. , (United States)
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, China. , (China)
  • 3 Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, 32610, United States. , (United States)
  • 4 Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, 32610, United States; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, 32610, United States; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL, 32610, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Analytical Biochemistry
Publisher
Elsevier
Publication Date
Dec 01, 2019
Volume
586
Pages
113413–113413
Identifiers
DOI: 10.1016/j.ab.2019.113413
PMID: 31479631
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The Hippo signaling pathway controls cell-cell contact, cell proliferation, as well as organ size by integrating changes in the cellular microenvironment. In recent years, the pivotal role of Hippo signaling in cancers has been well recognized. Inhibition of the pathway promotes the translocation of the major Hippo pathway effectors, the yes-associated protein (YAP) and its paralog TAZ, to the nucleus, where they interact with the transcription factor family transcriptional enhancer associate domain (TEAD), thus coactivating the expression of downstream genes, leading to cell transformation, tissue overgrowth, and tumor development. Therefore, the interruption of the YAP-TEAD transcriptional complex represents a novel opportunity for the treatment of cancer. Here, we established a fluorescence polarization (FP)-based assay for the identification and evaluation of YAP-TEAD protein-protein interface (PPI) inhibitors at the YAP Ω-loop binding region of TEAD, which is also called interface 3 at the YAP-TEAD binding surface. Furthermore, a patented small molecule (Patent-22) was evaluated by the FP assay, which confirmed that it was a YAP-TEAD PPI inhibitor at interface 3. Possessing great application value, this FP method is reliable, robust, and economical for inhibitor assessment and drug discovery. Copyright © 2019 Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times