Small-molecule compounds targeting the STAT3 DNA-binding domain suppress survival of cisplatin-resistant human ovarian cancer cells by inducing apoptosis

Wei Huang, Yuan Liu, Jun Wang, Xia Yuan, Hong Wei Jin, Liang Ren Zhang, Jian-Ting Zhang, Zhen Ming Liu, Jing Rong Cui

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) plays important roles in oncogenic occurrence and transformation by regulating the expression of diverse downstream target genes important for tumor growth, metastasis, angiogenesis and immune evasion. Feasibility of targeting the DNA-binding domain (DBD) of STAT3 has been proven previously. With the aid of 3D shape- and electrostatic-based drug design, we identified a new STAT3 inhibitor, LC28, and its five analogs, based on the pharmacophore of a known STAT3 DBD inhibitor. Microscale thermophoresis assay shows that these compounds inhibits STAT3 binding to DNA with a Ki value of 0.74–8.87 μM. Furthermore, LC28 and its analogs suppress survival of cisplatin-resistant ovarian cancer cells by inhibiting STAT3 signaling and inducing apoptosis. Therefore, these compounds may serve as candidate compounds for further modification and development as anticancer therapeutics targeting the DBD of human STAT3 for treatment of cisplatin-resistant ovarian cancer.

Original languageEnglish (US)
Pages (from-to)887-897
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume157
DOIs
StatePublished - Sep 5 2018

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STAT3 Transcription Factor
Ovarian Neoplasms
Cisplatin
Cells
Apoptosis
Molecules
Survival
DNA
Thermophoresis
Immune Evasion
Drug Design
Static Electricity
Tumors
Electrostatics
Assays
Genes
Chemical activation
Neoplasm Metastasis
Growth
Pharmaceutical Preparations

Keywords

  • Cisplatin resistance
  • DNA binding domain (DBD)
  • Microscale thermophoresis
  • Signal transducer and activator of transcription 3 (STAT3)
  • Similarity screening

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Small-molecule compounds targeting the STAT3 DNA-binding domain suppress survival of cisplatin-resistant human ovarian cancer cells by inducing apoptosis. / Huang, Wei; Liu, Yuan; Wang, Jun; Yuan, Xia; Jin, Hong Wei; Zhang, Liang Ren; Zhang, Jian-Ting; Liu, Zhen Ming; Cui, Jing Rong.

In: European Journal of Medicinal Chemistry, Vol. 157, 05.09.2018, p. 887-897.

Research output: Contribution to journalArticle

Huang, Wei ; Liu, Yuan ; Wang, Jun ; Yuan, Xia ; Jin, Hong Wei ; Zhang, Liang Ren ; Zhang, Jian-Ting ; Liu, Zhen Ming ; Cui, Jing Rong. / Small-molecule compounds targeting the STAT3 DNA-binding domain suppress survival of cisplatin-resistant human ovarian cancer cells by inducing apoptosis. In: European Journal of Medicinal Chemistry. 2018 ; Vol. 157. pp. 887-897.
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AU - Zhang, Liang Ren

AU - Zhang, Jian-Ting

AU - Liu, Zhen Ming

AU - Cui, Jing Rong

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