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Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf.

Authors :
Chen KF
Tai WT
Huang JW
Hsu CY
Chen WL
Cheng AL
Chen PJ
Shiau CW
Source :
European journal of medicinal chemistry [Eur J Med Chem] 2011 Jul; Vol. 46 (7), pp. 2845-51. Date of Electronic Publication: 2011 Apr 14.
Publication Year :
2011

Abstract

STAT3 is a transcription factor that modulates survival-directed transcription. It is persistently activated in many human cancers. Literature has shown that sorafenib, Raf kinase inhibitor, reduces Phospho-STAT3 and induces cell death. A series of sorafenib derivatives were synthesized as new inhibitors for STAT3. Urea, sulfonamide, and carboxamide linkers brought out different SARs from the end of sorafenib. Urea and carboxamide linked derivatives showed greater inhibition against STAT3 activity than sulfonamide linked derivatives. In particular, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)phenyl)urea (1), a urea linker, was as potent as sorafenib in reducing P-STAT3 level and cell death but no inhibition for Raf activity. Such result provides a new lead for the design of STAT3 inhibitors.<br /> (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Details

Language :
English
ISSN :
1768-3254
Volume :
46
Issue :
7
Database :
MEDLINE
Journal :
European journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
21531053
Full Text :
https://doi.org/10.1016/j.ejmech.2011.04.007