UM  > 中華醫藥研究院
Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening
Leung K.-H.1; Liu L.-J.3; Lin S.1; Lu L.1; Zhong H.-J.3; Susanti D.2; Rao W.2; Wang M.1; Che W.I.3; Chan D.S.H.1; Leung C.-H.3; Chan P.W.H.2; Ma D.-L.1
2015
Source PublicationMethods
ISSN10959130 10462023
Volume71Issue:CPages:38-43
AbstractSTAT3 modulates the transcription of a wide variety of regulatory genes involved in cell proliferation, differentiation, migration, apoptosis, and other critical cellular functions. Constitutive activation of STAT3 has been detected in a wide spectrum of human malignancies. A pharmacophore model constructed from a training set of STAT3 inhibitors binding to the SH2 domain was used to screen an in-house database of compounds, from which azepine 1 emerged as a top candidate. Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with comparable potency to the well-known STAT3 inhibitor S3I-201. A fluorescence polarization assay revealed that compound 1 targeted the SH2 domain of STAT3. Furthermore, compound 1 inhibited STAT3 phosphorylation in cells without affecting the total expression of STAT3. This study also validates the use of pharmacophore modeling to identify inhibitors of protein-protein interactions.
KeywordPharmacophore Protein-protein interaction STAT3 Virtual screening
DOI10.1016/j.ymeth.2014.07.010
URLView the original
Language英語
Fulltext Access
Citation statistics
Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Hong Kong Baptist University
2.Nanyang Technological University
3.University of Macau
Recommended Citation
GB/T 7714
Leung K.-H.,Liu L.-J.,Lin S.,et al. Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening[J]. Methods,2015,71(C):38-43.
APA Leung K.-H..,Liu L.-J..,Lin S..,Lu L..,Zhong H.-J..,...&Ma D.-L..(2015).Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening.Methods,71(C),38-43.
MLA Leung K.-H.,et al."Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening".Methods 71.C(2015):38-43.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Leung K.-H.]'s Articles
[Liu L.-J.]'s Articles
[Lin S.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Leung K.-H.]'s Articles
[Liu L.-J.]'s Articles
[Lin S.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Leung K.-H.]'s Articles
[Liu L.-J.]'s Articles
[Lin S.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.