PN-943
Also known as: Protagonist, oral α4β7 antagonist
An investigational oral, gut-restricted α4β7 integrin antagonist peptide for ulcerative colitis. Not approved; deprioritized by Protagonist in 2022.
Last updated
Mechanism of Action
PN-943 is an orally delivered, gastrointestinal-restricted peptide that binds the α4β7 integrin on circulating gut-homing lymphocytes. Blocking α4β7 prevents it from engaging MAdCAM-1 on intestinal blood vessels, reducing lymphocyte trafficking into inflamed bowel tissue. This is the same target as the injectable antibody vedolizumab, but PN-943 was designed to act locally in the gut with low systemic exposure.
- Half-life
- Not well established
- Administration Routes
- Oral
- Research Status
- Clinical
Reported Benefits
- Studied for induction of remission in moderate-to-severe ulcerative colitis
- Phase 1 showed dose-dependent α4β7 receptor occupancy in blood
- Phase 2 IDEAL trial did not meet its primary endpoint; the 150 mg twice-daily arm showed a numerical remission advantage over placebo
Potential Side Effects
- Reported as generally well tolerated in Phase 1 and Phase 2 studies
- Safety in larger and longer trials is unknown
- Long-term safety not established
Common Dosing
No approved dose; trial regimens have used oral doses of 150 mg or 450 mg twice daily in adults with ulcerative colitis.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Investigational: not established
No documented stacking partners for PN-943 yet.
- View
Single- and Multiple-Dose Pharmacokinetics and Pharmacodynamics of PN-943, a Gastrointestinal-Restricted Oral Peptide Antagonist of α4β7, in Healthy Volunteers
2021