Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors

Philias Daka, Aiguo Liu, Chamini V. Karunaratne, Erika Csatary, Cameron Williams, Hui Xiao, Jiayuh Lin, Zhenghu Xu, Richard C. Page, Hong Wang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inhibition of the signaling pathways of signal transducer and activator of transcription 3 (STAT 3) has shown to be a promising strategy to combat cancer. In this paper we report the design, synthesis and evaluation of a novel class of small molecule inhibitors, that is, XZH-5 and its analogues, as promising leads for further development of STAT3 inhibitors. Preliminary SARs was established for XZH-5 and its derivatives; and the binding modes were predicted by molecular docking. Lead compounds with IC50 as low as 6.5 μM in breast cancer cell lines and 7.6 μM in pancreatic cancer cell lines were identified.

Original languageEnglish (US)
Pages (from-to)1348-1355
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number6
DOIs
StatePublished - Mar 15 2015
Externally publishedYes

Fingerprint

Cells
Lead compounds
Cell Line
STAT3 Transcription Factor
Pancreatic Neoplasms
Inhibitory Concentration 50
Breast Neoplasms
Derivatives
Molecules
Neoplasms
Lead

Keywords

  • Inhibitor
  • Molecular docking
  • SARs
  • SH2
  • Small organic molecule
  • STAT3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Daka, P., Liu, A., Karunaratne, C. V., Csatary, E., Williams, C., Xiao, H., ... Wang, H. (2015). Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors. Bioorganic and Medicinal Chemistry, 23(6), 1348-1355. https://doi.org/10.1016/j.bmc.2015.01.025

Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors. / Daka, Philias; Liu, Aiguo; Karunaratne, Chamini V.; Csatary, Erika; Williams, Cameron; Xiao, Hui; Lin, Jiayuh; Xu, Zhenghu; Page, Richard C.; Wang, Hong.

In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 6, 15.03.2015, p. 1348-1355.

Research output: Contribution to journalArticle

Daka, P, Liu, A, Karunaratne, CV, Csatary, E, Williams, C, Xiao, H, Lin, J, Xu, Z, Page, RC & Wang, H 2015, 'Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors', Bioorganic and Medicinal Chemistry, vol. 23, no. 6, pp. 1348-1355. https://doi.org/10.1016/j.bmc.2015.01.025
Daka P, Liu A, Karunaratne CV, Csatary E, Williams C, Xiao H et al. Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors. Bioorganic and Medicinal Chemistry. 2015 Mar 15;23(6):1348-1355. https://doi.org/10.1016/j.bmc.2015.01.025
Daka, Philias ; Liu, Aiguo ; Karunaratne, Chamini V. ; Csatary, Erika ; Williams, Cameron ; Xiao, Hui ; Lin, Jiayuh ; Xu, Zhenghu ; Page, Richard C. ; Wang, Hong. / Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors. In: Bioorganic and Medicinal Chemistry. 2015 ; Vol. 23, No. 6. pp. 1348-1355.
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