Related Experiment Video

Updated: Feb 11, 2026

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
07:57

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors

Published on: January 20, 2023

6.8K

Discovery of new benzensulfonamide derivatives as tripedal STAT3 inhibitors

Jianpeng Guo1, Wenying Yu1, Guiping Cai1

  • 1Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.

European Journal of Medicinal Chemistry
|April 21, 2018
PubMed

Insights

Researchers developed a novel benzensulfanilamide derivative that selectively inhibits Signal Transducer and Activator of Transcription 3 (STAT3) activation. This compound effectively suppressed cancer cell growth and tumor development in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) is linked to cancer development.
  • STAT3 signaling pathway inhibition is a promising anti-cancer therapeutic strategy.
  • Selective STAT3 inhibitors are challenging to discover, as STAT1 and STAT3 have opposing roles in tumorigenesis.

Purpose of the Study:

  • To design and synthesize small-molecule benzensulfanilamide derivatives targeting STAT3 activation.
  • To identify selective STAT3 inhibitors for potential anti-cancer therapy.

Main Methods:

  • Design and synthesis of small-molecule benzensulfanilamide derivatives (MW < 500).
  • Evaluation of compound inhibitory effects on STAT3 phosphorylation (overexpressed and IL-6 induced).
  • Assessment of compound selectivity against other STAT isoforms (STAT1, STAT5).
  • In vitro assays for STAT3 DNA binding activity, colony formation, ROS levels, and apoptosis.
  • In vivo efficacy study using a mouse-xenograft model.

Main Results:

  • Compound 11 selectively inhibited STAT3 phosphorylation without affecting STAT1 or STAT5.
  • Compound 11 reduced STAT3 DNA binding activity and colony formation in cancer cells.
  • Compound 11 induced apoptosis and elevated reactive oxygen species (ROS) levels.
  • Compound 11 demonstrated significant tumor growth suppression in vivo.

Conclusions:

  • Benzensulfanilamide derivative 11 is a potent and selective STAT3 inhibitor.
  • Compound 11 exhibits anti-cancer properties through multiple mechanisms, including apoptosis induction.
  • This compound shows therapeutic potential for treating cancers driven by STAT3 activation.
Keywords:
Antitumor activityApoptosisSTAT3 phosphorylationSelectivityStructure-based drug designSulfonamide

More Related Videos

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

5.2K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.8K

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.1K
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
11.8K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
693
Measurement: Derived Units03:02

Measurement: Derived Units

The International System of Units or SI system, by international agreement, has fixed measurement units for seven fundamental properties: length, mass, time, temperature, electric current, amount of substance, and luminosity. These are called the SI base units.
56.0K
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
1.6K
Higher Derivatives01:29

Higher Derivatives

In calculus, higher-order derivatives extend the idea of differentiation beyond the first derivative to capture successive rates of change. These derivatives provide detailed information about the behavior of functions and have important applications in both mathematics and physics. To illustrate these concepts, consider the example functionwhich serves as a useful case study for exploring higher derivatives.The first derivative represents the slope of the original function. The second...
115