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

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

doi:10.1016/j.bmc.2015.01.025

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

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

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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 language	English (US)
Pages (from-to)	1348-1355
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	6
DOIs	https://doi.org/10.1016/j.bmc.2015.01.025
State	Published - Mar 15 2015
Externally published	Yes

Keywords

Inhibitor
Molecular docking
SARs
SH2
STAT3
Small organic molecule

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmc.2015.01.025

Cite this

@article{49b8cc7be984464db60e39982b75c3ba,

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

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.",

keywords = "Inhibitor, Molecular docking, SARs, SH2, STAT3, Small organic molecule",

author = "Philias Daka and Aiguo Liu and Chamini Karunaratne and Erika Csatary and Cameron Williams and Hui Xiao and Jiayuh Lin and Zhenghu Xu and Page, {Richard C.} and Hong Wang",

year = "2015",

month = mar,

day = "15",

doi = "10.1016/j.bmc.2015.01.025",

language = "English (US)",

volume = "23",

pages = "1348--1355",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "6",

}

TY - JOUR

T1 - Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors

AU - Daka, Philias

AU - Liu, Aiguo

AU - Karunaratne, Chamini

AU - Csatary, Erika

AU - Williams, Cameron

AU - Xiao, Hui

AU - Lin, Jiayuh

AU - Xu, Zhenghu

AU - Page, Richard C.

AU - Wang, Hong

PY - 2015/3/15

Y1 - 2015/3/15

N2 - 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.

AB - 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.

KW - Inhibitor

KW - Molecular docking

KW - SARs

KW - SH2

KW - STAT3

KW - Small organic molecule

UR - http://www.scopus.com/inward/record.url?scp=84923608705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923608705&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2015.01.025

DO - 10.1016/j.bmc.2015.01.025

M3 - Article

C2 - 25698618

AN - SCOPUS:84923608705

SN - 0968-0896

VL - 23

SP - 1348

EP - 1355

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this