Iseganan
An antimicrobial peptide mouth rinse that killed oral bacteria fast in people but failed to prevent mouth ulcers or ventilator pneumonia in phase 3
Iseganan (IB-367) is a synthetic antimicrobial peptide modelled on protegrin-1, a natural peptide that kills bacteria and fungi by breaking their membranes. IntraBiotics developed it as a swish-and-swallow rinse to stop the mouth ulcers caused by cancer treatment, on the theory that mouth bacteria make those ulcers worse. In people it cut the bacteria in the mouth sharply and was not absorbed into the blood. But in three phase 3 trials it did not reliably prevent oral mucositis, and in a 709-patient trial it did not prevent ventilator-associated pneumonia. It was never approved.
Used in human trials: 9 mg oral rinse, Six times daily, swish and swallow, Oral rinse (Study: PROMPT-CT, patients starting high-dose chemotherapy) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Protegrins are short natural antimicrobial peptides with a stiff hairpin shape, held together by two disulfide bridges, that punch through the membranes of bacteria and yeasts. Its developers made several hundred variants to learn which features mattered. The hairpin and its two-faced, oily-and-charged layout were essential, the exact amino acids much less so; even a version made entirely of D-amino acids worked. From that work, and from a hamster model of mouth ulcers, they chose one analogue, IB-367, for development as a topical drug. It was later named iseganan.
Its laboratory profile was strong. It killed the bacteria found in the mouth, including methicillin-resistant Staphylococcus aureus and Pseudomonas, within minutes, and bacteria exposed to it repeatedly became only slightly less sensitive. In pooled human saliva it cut the natural flora ten-thousand-fold in two minutes. In a phase 1 study in healthy volunteers, one rinse reduced the dominant mouth bacteria a thousand-fold, and no drug was detected in the blood. In hamsters, rinsing with it lowered both mouth bacteria and ulcer scores after chemotherapy.
The clinical trials tested the idea that killing mouth bacteria would prevent oral mucositis, the painful ulceration caused by chemotherapy and radiotherapy. In the PROMPT-CT trial in 323 patients having high-dose chemotherapy, 43% on iseganan against 33% on placebo stayed free of ulcers, a difference that missed statistical significance; a computer error had sent the wrong drug to about a third of patients. Pain scores were somewhat lower. A second chemotherapy trial in 502 patients found no significant difference on its primary endpoint or any other measure.
In 545 patients receiving radiotherapy for head-and-neck cancer, the result was the same: 9% on iseganan and 9% on placebo stayed free of ulcers. Both groups did better than standard care alone, which the authors attributed to the extra oral hygiene or the rinse vehicle itself, and they concluded that killing bacteria may not change how radiation ulcers form. A 2024 analysis of oral-mucositis drug programmes lists iseganan among the failed phase 3 trials.
The last test was in intensive care. Ventilator-associated pneumonia often starts with bacteria from the mouth, so 709 ventilated patients had iseganan or placebo applied to the mouth six times a day for up to 14 days. Pneumonia among survivors at day 14 was 16% with iseganan and 20% with placebo, not a significant difference, and day-14 deaths were 22.1% against 18.2%, also not significantly different. The authors concluded it was not effective, and a 2013 meta-analysis found that oral decontamination worked when antibiotics other than iseganan were used. Development stopped. The rinse amount below is from the chemotherapy trials and is history, not a treatment.
Mechanism of Action
Iseganan is a membrane-active antimicrobial peptide. Its positive charge draws it to the negatively charged surfaces of bacteria and fungi, and its two-faced hairpin structure disrupts their membranes.
Membrane disruption
Rapid killing of gram-positive and gram-negative bacteria and yeasts, within minutes (PMIDs 10858334, 18073150).
Endotoxin binding
Neutralised bacterial endotoxin in rat sepsis models (PMIDs 15019206, 12740345).
Stays in the mouth
Not detected in blood after oral rinsing (PMIDs 10858334, 12916869).
Published Research
These are studies of iseganan (IB-367) itself, read from their PubMed abstracts: the phase 3 trials in chemotherapy, radiotherapy and ventilated patients, the phase 1 and microbiology work, animal infection and endotoxin models, and reviews and analyses that discuss its trials. Studies of protegrin-1 or other protegrin analogues are not carded here.
Radiotherapy mucositis: no better than placebo
545 patients having radiotherapy for head-and-neck cancer received iseganan rinse plus standard oral care, placebo rinse plus standard care, or standard care alone. 9% on iseganan and 9% on placebo avoided ulcerative mucositis, against 2% on standard care alone. Pain and swallowing were no better with iseganan than placebo. Nausea was slightly more common with iseganan (51% vs 42%).
Ventilator-associated pneumonia: no benefit
709 mechanically ventilated patients in the US and Europe had iseganan or placebo applied to the mouth six times daily for up to 14 days. Pneumonia among survivors at day 14 was 16% against 20% (p = 0.145), and day-14 mortality 22.1% against 18.2% (p = 0.206). No excess of side effects was seen, and the authors concluded it did not improve outcomes.
PROMPT-CT: chemotherapy mucositis
323 patients starting high-dose chemotherapy rinsed with iseganan 9 mg or placebo six times daily for 21 to 28 days. 43% against 33% avoided ulcerative mucositis (P = 0.067), a miss on significance; a dispensing error affected 32% of patients. Mouth and throat pain and stomatitis scores were lower with iseganan, and no drug was found in the blood.
Second chemotherapy trial: no difference
502 patients receiving stomatotoxic chemotherapy, many with stem cell transplants, rinsed with iseganan 9 mg or placebo six times daily for up to 21 days. 43% and 37% avoided grade 2 or worse stomatitis (P = 0.182), and stomatitis severity, ulcers, pain, swallowing, opioid use and side effects did not differ.
It did kill mouth bacteria
In 225 patients from a phase 3 chemotherapy trial, cultures showed a 1.59 log drop in total oral microbes after the first day of iseganan against 0.18 log on placebo, mostly in streptococci and yeasts, with a cumulative effect by the last day. Its minimum inhibitory concentration against the flora did not change during treatment.
Lab activity and the phase 1 rinse
IB-367 inhibited oral gram-positive and gram-negative bacteria at low concentrations, killed MRSA and Pseudomonas by over 3 logs in under 16 minutes, and showed little resistance after repeated exposure. In healthy volunteers it was well tolerated with no detectable absorption, and an hour after one 9 mg rinse the main gram-positive flora was down a thousand-fold.
Hamster model of mouth ulcers
In hamsters given 5-fluorouracil and a scratched cheek pouch, topical IB-367 five or six times a day lowered mucositis scores at 0.5 and 2.0 mg/mL against placebo, cut oral bacteria more than 100-fold, and reduced severity in a dose-dependent way.
Septic shock models in rats
In three rat models of septic shock (endotoxin, live E. coli and caecal puncture), injected IB-367 had weaker antibacterial action than piperacillin but also neutralised endotoxin, and the two together worked best.
Endotoxin in jaundiced rats
In rats with a tied-off bile duct given endotoxin, IB-367 lowered plasma endotoxin and TNF-alpha and cut deaths to 10%, against 55% to 60% with placebo or piperacillin-tazobactam.
Catheter biofilm in rats
Filling central venous catheters in rats with IB-367 before challenge with Staphylococcus aureus or Enterococcus faecalis made linezolid lock therapy far more effective against biofilm, and no bacteria were found in the blood.
MRSA wounds in mice
Pretreating MRSA-infected mouse wounds with IB-367 before daptomycin or teicoplanin gave a 4-log drop in bacteria against 2 logs with the antibiotics alone, along with higher natural killer cell activity.
Gram-negative wounds
IB-367 killed Pseudomonas aeruginosa and E. coli isolates within 40 minutes in the dish and acted synergistically with colistin and imipenem; in infected mouse wounds, topical IB-367 with injected colistin reduced bacterial loads the most.
Candida isolates
Against 25 clinical Candida isolates, including fluconazole-resistant ones, IB-367 had MICs of 2 to 32 micrograms per mL, killed quickly, and acted synergistically with fluconazole or amphotericin B in over 40% of pairings, with no antagonism.
The developers' case before phase 3 results
Written while trials were running, this review lists iseganan's rapid broad-spectrum killing, lack of observed resistance, stability and lack of absorption, describes early benefit in transplant patients, and names ventilator pneumonia and inhaled use in cystic fibrosis as next targets.
Dosing Data
Iseganan was never approved and its development ended. These are the rinse amounts used in its chemotherapy trials and phase 1 study, as stated in their abstracts. The radiotherapy and ventilator trial abstracts give the schedule (six times a day) but not the amount, so they have no row.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Iseganan is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: oral rinse). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Iseganan, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Iseganan stays intact once mixed.
How it is taken
As it was given in human studies: Oral rinse (Six times daily, swish and swallow; Study: PROMPT-CT, patients starting high-dose chemotherapy).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: PROMPT-CT, patients starting high-dose chemotherapy: 21 to 28 days from the start of chemotherapy; Study: stomatotoxic chemotherapy, 502 patients: Up to 21 days; Study: phase 1, healthy volunteers: One dose.
When effects appear: unknown; no source on this page gives a time to effect for Iseganan. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Nausea slightly more common than with placebo in radiotherapy patients, 51% against 42% (PMID 14967419); No excess adverse events over placebo in ventilated patients; day-14 deaths 22.1% against 18.2%, not significantly different (PMID 16192451); Adverse events no different from placebo in chemotherapy patients (PMID 15120931). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Iseganan. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the phase 3 trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Iseganan (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Iseganan products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Iseganan's expected mass, 1,900.3 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (Never approved: Drugs@FDA and the EMA medicines list hold no record (searched October 28, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the phase 3 trials above.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Iseganan was never approved, and its development ended after its phase 3 trials.
Frequently Asked Questions
?What is iseganan?
A synthetic antimicrobial peptide modelled on protegrin-1. It kills bacteria and yeasts by breaking their membranes and was developed as a mouth rinse.
?Did iseganan prevent mouth ulcers during cancer treatment?
No. In radiotherapy patients it did no better than placebo, and in two chemotherapy trials the main results were not statistically significant, though pain scores were somewhat lower in one.
?Did it kill mouth bacteria?
Yes. Oral bacterial counts dropped sharply after rinsing, and the bacteria did not become resistant during treatment. That did not translate into fewer ulcers.
?Did it prevent pneumonia on a ventilator?
No. In 709 ventilated patients, pneumonia and deaths at day 14 did not differ significantly from placebo.
?Is it absorbed into the body?
No drug was detected in the blood after rinsing in the phase 1 study or the PROMPT-CT trial.
?Is iseganan available anywhere?
No. It was never approved and development stopped after the phase 3 trials.
References
- [other] PubChem CID 16131103, Iseganan: formula C78H126N30O18S4, molecular weight 1900.3. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/16131103
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT00022373 (phase 3, oral mucositis, status unknown) and NCT00118781 (phase 2/3, ventilator-associated pneumonia, terminated).
- [clinical-trial] Trotti A, et al. "A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy." Int J Radiat Oncol Biol Phys, 2004;58(3):674-81. PMID: 14967419.
- [clinical-trial] Kollef M, et al. "A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia." Am J Respir Crit Care Med, 2006;173(1):91-7. PMID: 16192451.
- [clinical-trial] Giles FJ, et al. "A phase III, randomized, double-blind, placebo-controlled, multinational trial of iseganan for the prevention of oral mucositis in patients receiving stomatotoxic chemotherapy (PROMPT-CT trial)." Leuk Lymphoma, 2003;44(7):1165-72. PMID: 12916869.
- [clinical-trial] Giles FJ, et al. "A phase III, randomized, double-blind, placebo-controlled, study of iseganan for the reduction of stomatitis in patients receiving stomatotoxic chemotherapy." Leuk Res, 2004;28(6):559-65. PMID: 15120931.
- [clinical-trial] Elad S, et al. "The antimicrobial effect of Iseganan HCl oral solution in patients receiving stomatotoxic chemotherapy: analysis from a multicenter, double-blind, placebo-controlled, randomized, phase III clinical trial." J Oral Pathol Med, 2012;41(3):229-34. PMID: 22077420.
- [pubmed] Mosca DA, et al. "IB-367, a protegrin peptide with in vitro and in vivo activities against the microflora associated with oral mucositis." Antimicrob Agents Chemother, 2000;44(7):1803-8. PMID: 10858334.
- [pubmed] Loury D, et al. "Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters." Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1999;87(5):544-51. PMID: 10348510.
- [pubmed] Giacometti A, et al. "Antiendotoxin activity of protegrin analog IB-367 alone or in combination with piperacillin in different animal models of septic shock." Peptides, 2003;24(11):1747-52. PMID: 15019206.
- [pubmed] Giacometti A, et al. "Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats." Gut, 2003;52(6):874-8. PMID: 12740345.
- [pubmed] Ghiselli R, et al. "Pretreatment with the protegrin IB-367 affects Gram-positive biofilm and enhances the therapeutic efficacy of linezolid in animal models of central venous catheter infection." JPEN J Parenter Enteral Nutr, 2007;31(6):463-8. PMID: 17947600.
- [pubmed] Cirioni O, et al. "IB-367 pre-treatment improves the in vivo efficacy of teicoplanin and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus." J Med Microbiol, 2013;62(Pt 10):1552-1558. PMID: 23813277.
- [pubmed] Simonetti O, et al. "In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria." Peptides, 2014;55:17-22. PMID: 24531033.
- [pubmed] Barchiesi F, et al. "In-vitro activity of the synthetic protegrin IB-367 alone and in combination with antifungal agents against clinical isolates of Candida spp." J Chemother, 2007;19(5):514-8. PMID: 18073150.
- [review] Giles FJ, et al. "Iseganan HCl: a novel antimicrobial agent." Expert Opin Investig Drugs, 2002;11(8):1161-70. PMID: 12150709.
- [clinical-trial] Cella D, et al. "Evaluation of pain associated with oral mucositis during the acute period after administration of high-dose chemotherapy." Cancer, 2003;98(2):406-12. PMID: 12872363.
- [pubmed] Chen J, et al. "Development of protegrins for the treatment and prevention of oral mucositis: structure-activity relationships of synthetic protegrin analogues." Biopolymers, 2000;55(1):88-98. PMID: 10931444.
- [review] Li J, et al. "Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials." J Hosp Infect, 2013;84(4):283-93. PMID: 23846238.
- [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.
- [review] Anonymous, et al. "Iseganan. IB 367, protegrin IB 367." Drugs R D, 2002;3(1):52-5. PMID: 11881532.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Identity data come from PubChem (CID 16131103); trial status from ClinicalTrials.gov and regulatory status from Drugs@FDA (openFDA) and the EMA medicines list. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.