PN-943
Oral α4β7 integrin antagonist peptide
Also PN943, PN 943, Oral alpha4beta7 antagonist
- Evidence
- CAnimal and cell studies
- FDA status
- In clinical trialsas of 2026-10-27
- Route
- Oral
- Studies cited
- 2 human1 animal or cell
A pill meant to treat ulcerative colitis, a bowel disease. In a trial of 159 people it missed its main goal at the higher dose and only narrowly helped at the lower one.
Sold for
PN-943 was pitched as an oral, gut-restricted pill that could do what vedolizumab infusions do for ulcerative colitis.
Studies say
The one controlled trial in ulcerative colitis failed its primary endpoint at the higher dose and showed only a borderline signal at the lower one, so the evidence does not support the claimed use.
Why grade C. PN-943 has been through phase 1 in healthy volunteers and one randomized, placebo-controlled phase 2 trial in 159 adults with ulcerative colitis, which missed its primary endpoint at the higher dose. A randomized trial exists, but it did not show benefit on its main outcome, so there is no controlled evidence supporting the intended use. The predecessor compound PTG-100 has separate preclinical and phase 2a data. 12
FDA. PN-943 is an investigational oral peptide that is not approved by the FDA for any use. After the phase 2 IDEAL trial in ulcerative colitis reported in 2022, its sponsor, Protagonist Therapeutics, said it would put no further internal resources into the program and would look for a licensing partner. No phase 3 trial has been registered.
Written from 3 cited sources. Fact-checked 2026-10-27: 14 claims checked, 3 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Calming ulcerative colitis.
- Can a US doctor prescribe it?
- No. It is not approved, and its maker is looking for a partner to take it on.
- Properly tested in people?
- Not properly: animal or lab studies, or small uncontrolled human reports. one 159-person trial that missed its main goal.
Evidence checklist
- Randomised controlled trial IDEAL phase 2, placebo-controlledyes
- Human study over 100 people IDEAL 159 adultsyes
- More than one research group Single sponsor, one trialno
- Clinical outcomes, not surrogate markers Missed remission endpoint at higher doseno
- Human safety data beyond case reports Press release data; 12 weeks onlyno
Drawn from the cited studies below. A dash means the sources give no information.
What it is
PN-943 is a lab-made peptide. It is meant to be swallowed and to act inside the gut without being absorbed. Protagonist Therapeutics engineered it as a more potent successor to PTG-100. PTG-100 was an earlier oral peptide with the same target. The company took it through a phase 2a trial in ulcerative colitis. 1
The target is the alpha4beta7 integrin. Vedolizumab (Entyvio) blocks the same protein. It is an injected antibody approved for ulcerative colitis and Crohn's disease. PN-943 aimed to deliver that mechanism in a pill. Exposure in the rest of the body would be minimal. 12
How it works
Alpha4beta7 integrin sits on the surface of certain immune cells (T lymphocytes). It lets them stick to MAdCAM-1, a molecule on blood vessel walls in the gut. That handshake is how inflammatory cells leave the bloodstream and enter gut tissue. PN-943 binds the integrin and blocks the handshake. This should reduce the flow of inflammatory cells into the bowel lining. The PTG-100 program used the same approach. It cut receptor availability on blood cells in a dose-dependent way. This is how researchers confirmed the drug was hitting its target despite low blood levels. 1
What human research shows
The phase 2 IDEAL trial randomized 159 adults with moderate to severe ulcerative colitis. They got a higher dose, a lower dose or placebo for 12 weeks. The higher dose did not meet the primary endpoint of clinical remission, which was set in advance. The lower dose beat placebo by 13 percentage points in the main analysis population. This did not reach statistical significance. In patients who had never had a biologic, the gap was 16 points. That did reach significance. Endoscopic and histologic measures moved the same way at the lower dose. Clinical remission was 27.5 percent at the lower dose versus 14.5 percent on placebo. The company said the results supported a phase 3 program. In November 2022 it said it would put no further internal resources into PN-943 and would look for a licensing partner. 23
Earlier, PTG-100 was the first-generation compound. It showed target engagement in healthy volunteers. It also showed a signal in a phase 2a ulcerative colitis trial. That trial had been stopped early for futility. A re-analysis of endoscopy readings then suggested an effect. That history is part of why the field treated the PN-943 result with caution. 1
| Study | Model | Finding |
|---|---|---|
| IDEAL phase 2 | Humans, n=159, randomized, double-blind, placebo-controlled, 12 weeks | The higher dose missed the primary endpoint of clinical remission; the lower dose gave 27.5% remission versus 14.5% on placebo, a 13 point difference that was not significant (P=0.08). 2 |
| PTG-100 preclinical and phase 1/2a | Humans (healthy volunteers and ulcerative colitis patients) plus animal models | The first-generation oral alpha4beta7 antagonist engaged its target in blood and showed a signal in ulcerative colitis after re-analysis. 1 |
Safety
In the phase 2 trial, adverse events were described as balanced between PN-943 and placebo. The sponsor's summary reported no serious safety signal. The peptide is barely absorbed. So side effects in the body were expected to be few. Only 159 patients were treated, for 12 weeks. The full trial has no peer-reviewed publication. So the safety picture is thin. It rests on a press release and a conference presentation. 2
Questions for your clinician
- Is there any trial showing PN-943 helps ulcerative colitis?
- What approved treatments might help my colitis?
- Are other oral peptide trials open for me?
Questions people ask
Is PN-943 FDA-approved?
No. It is an investigational compound that has not gone beyond phase 2. No phase 3 trial has been registered. Protagonist said in November 2022 that it would put no further internal resources into the program and would look for a licensing partner. 23
How is PN-943 related to vedolizumab?
Both block the alpha4beta7 integrin. This keeps inflammatory immune cells from entering the gut lining. Vedolizumab is an injected antibody approved for ulcerative colitis and Crohn's disease. PN-943 was an attempt to deliver the same mechanism as a pill that stays in the gut. 12
Why did the phase 2 trial fail?
The higher dose did not beat placebo on clinical remission. The lower dose fell just short of statistical significance in the main analysis. This could mean the drug has a small effect. It could mean the trial was too small. It could mean the oral approach does not deliver enough drug to the tissue. The data do not tell these apart. 2
Can PN-943 be bought online?
It is not approved anywhere. It is not a legitimate research chemical with a published synthesis in the public domain. Anything offered under that name has no verifiable origin. 2
Citations
- Sandborn 2021, Gastroenterology: PTG-100, an oral alpha4beta7 antagonist peptide, preclinical development and phase 1 and 2a studies in ulcerative colitis doi.org
- HCPLive 2022: phase 2 IDEAL trial results for PN-943 in ulcerative colitis hcplive.com
- BioSpace: Protagonist third quarter 2022 results and corporate update biospace.com