Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity

Siddiquee, Khandaker; Zhang, Shumin; Guida, Wayne C.; Blaskovich, Michelle A.; Greedy, Benjamin; Lawrence, Harshani R.; Yip, M.L. Richard; Jove, Richard; McLaughlin, Mark M.; Lawrence, Nicholas J.; Sebti, Saı̈d M.; Turkson, James

doi:10.1073/pnas.0609757104

articleProceedings of the National Academy of SciencesApr 27, 2007GREEN OA

Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity

KSKhandaker Siddiquee SZShumin Zhang WCWayne C. Guida MAMichelle A. Blaskovich BGBenjamin Greedy

University of Central Florida · Molecular Research Institute · +7 more institutions

PubMed

Indexed incrossrefdatacitepubmed

Abstract

S3I-201 (NSC 74859) is a chemical probe inhibitor of Stat3 activity, which was identified from the National Cancer Institute chemical libraries by using structure-based virtual screening with a computer model of the Stat3 SH2 domain bound to its Stat3 phosphotyrosine peptide derived from the x-ray crystal structure of the Stat3beta homodimer. S3I-201 inhibits Stat3.Stat3 complex formation and Stat3 DNA-binding and transcriptional activities. Furthermore, S3I-201 inhibits growth and induces apoptosis preferentially in tumor cells that contain persistently activated Stat3. Constitutively dimerized and active Stat3C and Stat3 SH2 domain rescue tumor cells from S3I-201-induced apoptosis. Finally, S3I-201 inhibits…

Citation impact

742

total citations

FWCI: 15.37
Percentile: 100%
References: 39

Citations per year

Authors

12

Topics & keywords

Topics

Keywords

Virtual screening
Chemistry
Cancer research
Medicine
Drug discovery
Biochemistry

UN Sustainable Development Goals

Good health and well-being

No related works found for this paper.