Dusquetide
An innate defense regulator for mouth sores caused by cancer treatment
Dusquetide is a synthetic five-amino-acid peptide, Arg-Ile-Val-Pro-Ala amide, developed as an 'innate defense regulator': rather than killing microbes, it adjusts how the body's first-line immune system responds. It halved severe oral mucositis in a phase 2 trial in head and neck cancer, but the 266-patient phase 3 trial missed its primary endpoint. A small Behçet's ulcer pilot followed in 2025.
What is it?
Innate defense regulators are short synthetic peptides that act on the host instead of on bacteria. Dusquetide's target is p62, an adaptor protein that sits where stress, autophagy and innate immune signals meet. A 2022 structural study showed the peptide entering cells and binding p62's ZZ domain, shifting signalling through the p62-RIP1 complex without switching on autophagy. In animal infection models it improved bacterial clearance and survival, worked alongside standard antibiotics, and moved cytokines toward a less damaging balance.
Its main clinical target was oral mucositis, the painful mouth ulceration that almost everyone receiving chemoradiation for head and neck cancer develops. Dusquetide shortened mucositis by about half in mouse and hamster models, and a randomized, placebo-controlled phase 2 trial reported a similar halving in the duration of severe oral mucositis, along with fewer infections. Long-term follow-up found it did not increase infection, tumour growth or deaths.
The phase 3 trial, DOM-INNATE, enrolled 266 patients and completed in 2021. A 2024 review of phase 3 mucositis trials counts it among the three failures, alongside iseganan and clonidine, because its primary endpoint did not reach statistical significance; the successes were palifermin and avasopasem. The review points to differences in sponsor funding, patient selection and endpoint choice between phase 2 and phase 3 as recurring reasons such trials fail.
Development moved to Behçet's syndrome. In an open-label pilot, 8 patients with oral ulcers despite colchicine received intravenous dusquetide twice weekly for four weeks; 7 reported fewer, shorter and less painful ulcers, and comparisons with historical placebo groups were favourable. There was no control group, and the sponsor's scientists are among the authors of every clinical study. Dusquetide is not approved anywhere.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Published Research
Studies of dusquetide, from their PubMed abstracts.
Phase 2a in head and neck cancer
Dusquetide reduced oral mucositis duration by about 50% in mouse and hamster models, matched by a 50% reduction in severe oral mucositis in a randomized, placebo-controlled phase 2 trial, with fewer infections.
Long-term phase 2 follow-up
Extended follow-up found dusquetide well tolerated and not associated with more infection, tumour growth or mortality in head and neck cancer patients receiving chemoradiation.
Behçet's syndrome pilot
In an open-label pilot of 8 patients with oral ulcers despite colchicine, intravenous dusquetide twice weekly for 4 weeks led 7 to report fewer, shorter and less painful ulcers; there were no treatment-related or serious adverse events.
Binding to p62
Dusquetide bound the ZZ domain of p62, penetrated cells, modulated the p62-RIP1 complex, increased p38 phosphorylation and C/EBP-beta expression, and did not activate autophagy.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
There is no label.
Legal Status
Dusquetide is investigational.
Frequently Asked Questions
?What is dusquetide?
An investigational five-amino-acid peptide, Arg-Ile-Val-Pro-Ala amide, that adjusts innate immune signalling by binding the adaptor protein p62. It is called an innate defense regulator.
?Does dusquetide work for oral mucositis?
A phase 2 trial reported a 50% reduction in severe oral mucositis, but the 266-patient phase 3 trial did not reach statistical significance on its primary endpoint.
?Is dusquetide an antimicrobial peptide like LL-37?
No. It does not kill bacteria directly. In animals it improved bacterial clearance by acting on the host's own cells, which is why it is grouped separately from antimicrobial peptides such as LL-37.
?What is SGX945?
The code used for dusquetide in Behçet's syndrome. An 8-patient open-label pilot completed in 2025 reported fewer and less painful oral ulcers, without a control group.
References
- [other] PubChem CID 122177130, Dusquetide: formula C25H47N9O5, molecular weight 553.7. Read October 3, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/122177130
- [fda] FDA. Drugs@FDA (openFDA): no application on record for dusquetide. Read October 3, 2026.
- [registry] ClinicalTrials.gov API v2, read October 3, 2026: NCT03237325 (DOM-INNATE, phase 3, 266 enrolled, completed 2021-06-24) and NCT06386744 (Behçet's disease, phase 2, 8 enrolled, completed 2025-06-17).
- [pubmed] Liang L, et al. "Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck." Drug Dev Res, 2024;85(3):e22188. PMID: 38678547.
- [clinical-trial] Kudrimoti M, et al. "Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study." J Biotechnol, 2016;239:115-125. PMID: 27746305.
- [pubmed] Kudrimoti M, et al. "Dusquetide: Reduction in oral mucositis associated with enduring ancillary benefits in tumor resolution and decreased mortality in head and neck cancer patients." Biotechnol Rep (Amst), 2017;15:24-26. PMID: 28649557.
- [clinical-trial] Donini O, et al. "Results from a pilot study of dusquetide for the treatment of aphthous ulcers associated with Behçet's syndrome." Rheumatology (Oxford), 2026;65(2). PMID: 41400947.
- [pubmed] Zhang Y, et al. "Dusquetide modulates innate immune response through binding to p62." Structure, 2022;30(8):1055-1061.e7. PMID: 35640615.
- [pubmed] North JR, et al. "A novel approach for emerging and antibiotic resistant infections: Innate defense regulators as an agnostic therapy." J Biotechnol, 2016;226:24-34. PMID: 27015977.
Sources & Citations
Studies were read from their PubMed records and trial registrations from ClinicalTrials.gov, October 3, 2026.
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