A novel small-molecule inhibitor of IL-6 signalling.

G. Zinzalla, M.R. Haque, B.P. Basu, J. Anderson, S.L. Kaye, Shozeb Haider, F. Hasan, D. Antonow, S. Essex, K.M. Rahman, J. Palmer, D. Morgenstern, A.F. Wilderspin, S. Neidle, D.E. Thurston

Research output: Contribution to journalArticle

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Abstract

A small library of pyrrolidinesulphonylaryl molecules has been synthesized via an efficient 4-step route, and members evaluated for their ability to inhibit IL-6 signalling. One molecule (6a) was found to have promising activity against IL-6/STAT3 signalling at the low micromolar level, and to selectively inhibit phosphorylation of STAT3 (but not STAT1) in IL-6 stimulated MDA-MB-231 breast cancer and HeLa cell lines. It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties.
Original languageEnglish
Pages (from-to)7029-7032
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Volume20(23)
Issue number23
DOIs
Publication statusPublished - 01 Dec 2010

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Interleukin-6
Molecules
Small Molecule Libraries
Null Lymphocytes
Phosphorylation
Cytostatic Agents
HeLa Cells
Cells
Breast Neoplasms
Cell Line

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Zinzalla, G., Haque, M. R., Basu, B. P., Anderson, J., Kaye, S. L., Haider, S., ... Thurston, D. E. (2010). A novel small-molecule inhibitor of IL-6 signalling. Bioorganic & Medicinal Chemistry Letters, 20(23)(23), 7029-7032. https://doi.org/10.1016/j.bmcl.2010.09.117
Zinzalla, G. ; Haque, M.R. ; Basu, B.P. ; Anderson, J. ; Kaye, S.L. ; Haider, Shozeb ; Hasan, F. ; Antonow, D. ; Essex, S. ; Rahman, K.M. ; Palmer, J. ; Morgenstern, D. ; Wilderspin, A.F. ; Neidle, S. ; Thurston, D.E. / A novel small-molecule inhibitor of IL-6 signalling. In: Bioorganic & Medicinal Chemistry Letters. 2010 ; Vol. 20(23), No. 23. pp. 7029-7032.
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author = "G. Zinzalla and M.R. Haque and B.P. Basu and J. Anderson and S.L. Kaye and Shozeb Haider and F. Hasan and D. Antonow and S. Essex and K.M. Rahman and J. Palmer and D. Morgenstern and A.F. Wilderspin and S. Neidle and D.E. Thurston",
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Zinzalla, G, Haque, MR, Basu, BP, Anderson, J, Kaye, SL, Haider, S, Hasan, F, Antonow, D, Essex, S, Rahman, KM, Palmer, J, Morgenstern, D, Wilderspin, AF, Neidle, S & Thurston, DE 2010, 'A novel small-molecule inhibitor of IL-6 signalling.', Bioorganic & Medicinal Chemistry Letters, vol. 20(23), no. 23, pp. 7029-7032. https://doi.org/10.1016/j.bmcl.2010.09.117

A novel small-molecule inhibitor of IL-6 signalling. / Zinzalla, G.; Haque, M.R.; Basu, B.P.; Anderson, J.; Kaye, S.L.; Haider, Shozeb; Hasan, F.; Antonow, D.; Essex, S.; Rahman, K.M.; Palmer, J.; Morgenstern, D.; Wilderspin, A.F.; Neidle, S.; Thurston, D.E.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 20(23), No. 23, 01.12.2010, p. 7029-7032.

Research output: Contribution to journalArticle

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AU - Zinzalla, G.

AU - Haque, M.R.

AU - Basu, B.P.

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AU - Kaye, S.L.

AU - Haider, Shozeb

AU - Hasan, F.

AU - Antonow, D.

AU - Essex, S.

AU - Rahman, K.M.

AU - Palmer, J.

AU - Morgenstern, D.

AU - Wilderspin, A.F.

AU - Neidle, S.

AU - Thurston, D.E.

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AB - A small library of pyrrolidinesulphonylaryl molecules has been synthesized via an efficient 4-step route, and members evaluated for their ability to inhibit IL-6 signalling. One molecule (6a) was found to have promising activity against IL-6/STAT3 signalling at the low micromolar level, and to selectively inhibit phosphorylation of STAT3 (but not STAT1) in IL-6 stimulated MDA-MB-231 breast cancer and HeLa cell lines. It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties.

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Zinzalla G, Haque MR, Basu BP, Anderson J, Kaye SL, Haider S et al. A novel small-molecule inhibitor of IL-6 signalling. Bioorganic & Medicinal Chemistry Letters. 2010 Dec 1;20(23)(23):7029-7032. https://doi.org/10.1016/j.bmcl.2010.09.117