@article{dcba2375beb3415a95a61c547ce93066,
title = "Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening",
abstract = "STAT3 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.",
keywords = "Pharmacophore, Protein-protein interaction, STAT3, Virtual screening",
author = "Leung, {Ka Ho} and Liu, {Li Juan} and Sheng Lin and Lihua Lu and Zhong, {Hai Jing} and Dewi Susanti and Weidong Rao and Modi Wang and Che, {Weng Ian} and Chan, {Daniel Shiu Hin} and Leung, {Chung Hang} and Chan, {Philip Wai Hong} and Ma, {Dik Lung}",
note = "Funding Information: This work is supported by Hong Kong Baptist University ( FRG2/12-13/021 and FRG2/13-14/008 ), Centre for Cancer and Inflammation Research, School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund ( HMRF/13121482 ), the Research Grants Council ( HKBU/201811 , HKBU/204612 , and HKBU/201913 ), the French National Research Agency/Research Grants Council Joint Research Scheme ( A-HKBU201/12 ), the Science and Technology Development Fund , Macau SAR ( 103/2012/A3 ), the University of Macau ( MYRG091(Y3-L2)-ICMS12-LCH , MYRG121(Y3-L2)-ICMS12-LCH and MRG023/LCH/2013/ICMS ), University Research Committee Grant ( RG55/06 ) from Nanyang Technological University and Science and Engineering Research Council Grant ( 092 101 0053 ) from A∗STAR , Singapore. ",
year = "2015",
doi = "10.1016/j.ymeth.2014.07.010",
language = "English",
volume = "71",
pages = "38--43",
journal = "Methods",
issn = "1046-2023",
publisher = "Academic Press Inc.",
number = "C",
}