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1. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Author:
Page, Brent D. G.,   et al.   ; Zhang, Xiaolei; Yue, Peibin; Li, Tianshu; Zhao, Wei; Namanja, Andrew T.; Paladino, David; Zhao, Jihe; Chen, Yuan; Gunning, Patrick T.; Turkson, James;     Show all 11 Authors
Source:
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.24 pp. 9623-9628
ISSN:
0027-8424
Subject:
antagonists; breast neoplasms; cadherins; cell adhesion; cell movement; cyclins; genes; granulocyte colony-stimulating factor; human growth; humans; interleukin-1; intravenous injection; lung neoplasms; macrophages; neoplasm cells; non-specific protein-tyrosine kinase; phosphorylation; pro-apoptotic proteins; proteinase inhibitors; serine proteinases; signal transduction; tissues; transactivators; vascular endothelial growth factors
Abstract:
... Computer-aided lead optimization derives a unique, orally bioavailable inhibitor of the signal transducer and activator of transcription (Stat)3 Src homology 2 domain. BP-1-102 binds Stat3 with an affinity (K D) of 504 nM, blocks Stat3–phospho-tyrosine (pTyr) peptide interactions and Stat3 activation at 4–6.8 μM, and selectively inhibits growth, survival, migration, and invasion of Stat3-dependent ...
DOI:
10.1073/pnas.1121606109
PubMed:
22623533
PubMed Central:
PMC3386073