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Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Selective STAT3 Allosteric Inhibitors HCB-5300 and HCB-5400 Alleviate Dextran Sulfate Sodium-Induced Ulcerative
Wook-Young Baek1, Ji-Won Kim1, So-Won Park2
1Department of Rheumatology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Novel STAT3 inhibitors, HCB-5300 and HCB-5400, effectively reduced inflammation and damage in a mouse model of inflammatory bowel disease (IBD). HCB-5400 demonstrated superior efficacy, highlighting its therapeutic potential for IBD flares.
Area of Science:
- Pharmacology
- Gastroenterology
- Immunology
Background:
- Inflammatory bowel disease (IBD) involves chronic gastrointestinal inflammation and damage.
- STAT3 signaling is a key pathway implicated in IBD pathogenesis.
Purpose of the Study:
- To evaluate the efficacy of novel selective STAT3 allosteric inhibitors, HCB-5300 and HCB-5400, in a dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model.
- To assess the anti-inflammatory effects and therapeutic potential of these inhibitors in IBD.
Main Methods:
- Ulcerative colitis was induced in C57BL/6 mice using 3% DSS.
- Mice were treated orally with HCB-5300 (25 mg/kg) or HCB-5400 (12.5 mg/kg) during DSS induction.
- Disease activity index (DAI), colon length, histopathology, and IL-6 levels were assessed.
Main Results:
- Both HCB-5300 and HCB-5400 significantly mitigated DSS-induced colitis, reducing body weight loss and improving DAI scores.
- Treatment preserved colon length and decreased mucosal damage and inflammation, with lower IL-6 levels observed.
- HCB-5400 showed superior efficacy across most evaluated parameters.
Conclusions:
- HCB-5300 and HCB-5400 are potent, selective STAT3 allosteric inhibitors with significant anti-inflammatory effects.
- HCB-5400 demonstrates promising therapeutic potential for managing inflammatory flares in IBD.
- These findings support further investigation of STAT3 allosteric inhibitors for IBD treatment.
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