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STAT3 Inhibitory Activity of Structurally Simplified Withaferin A Analogues
Teruyuki Tahara1, Ursula Streit1, Henry E Pelish1
1Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Abstract:
Signal transducer and activator of transcription 3 (STAT3) is a component of the JAK/STAT pathway. Therapeutic inhibition of STAT3 has been of high interest, as its aberrant activation has been linked to cancer, inflammation, and other human diseases. The withanolide family natural product withaferin A (1) inhibits STAT3 activation. We designed, synthesized, and evaluated simplified withanolide analogues SLW1 (3) and SLW2 (4), and found that SLW1 retained the STAT3 inhibitory activity of withaferin A.
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