dc.contributor.authorLeung, Ka-Ho
dc.contributor.authorLiu, Li-Juan
dc.contributor.authorLin, Sheng
dc.contributor.authorLu, Lihua
dc.contributor.authorZhong, Hai-Jing
dc.contributor.authorSusanti, Dewi
dc.contributor.authorRao, Weidong
dc.contributor.authorWang, Modi
dc.contributor.authorChe, Weng Ian
dc.contributor.authorChan, Daniel Shiu-Hin
dc.contributor.authorLeung, Chung-Hang
dc.contributor.authorChan, Philip Wai Hong
dc.contributor.authorMa, Dik-Lung
dc.identifier.citationLeung, K.-H., Liu, L.-J., Lin, S., Lu, L., Zhong, H.-J., Susanti, D., et al. (2014). Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening. Methods, 71, 38-43.en_US
dc.description.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.en_US
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en_US
dc.rights© 2014 Elsevier Inc.en_US
dc.titleDiscovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screeningen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Physical and Mathematical Sciencesen_US

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