Brimapitide
An all-D-amino-acid peptide that blocks the stress kinase JNK, tested in sudden deafness and eye-surgery inflammation
Brimapitide is a 31-residue peptide built from D-amino acids, the mirror forms that protein-cutting enzymes barely touch. One part of it is the stretch of the scaffold protein JIP1 that grips the stress kinase JNK; the other is the short sequence from HIV's TAT protein that carries cargo through cell membranes. Under the names AM-111 and XG-102 it was injected through the eardrum in two hearing-loss trials and under the conjunctiva after eye surgery. Neither the main phase 2 nor the phase 3 hearing trial met its primary goal in all patients; benefit appeared only in the most severe losses. It is not approved anywhere.
Used in human trials: 0.4 or 0.8 mg/mL, Single injection, Intratympanic injection (through the eardrum) (Study: sudden deafness, phase 3 (HEALOS)) 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?
JNK, short for c-Jun N-terminal kinase, is one of the enzymes cells switch on when they are injured by noise, loss of blood supply, toxins or inflammation, and its signalling helps push damaged cells toward programmed death. Brimapitide was designed to interrupt that step. It copies the small docking region of JIP1, a scaffold protein that holds JNK, so that the kinase cannot reach its targets, and it carries the TAT sequence from HIV, a run of arginines and lysines that lets the peptide slip into cells. Built from D-amino acids in reverse order, the so-called retro-inverso form, it resists digestion far better than the natural L-form it imitates.
Its first and longest-running use was the inner ear. Delivered in a gel through the eardrum onto the round window, it protected hearing in guinea pigs with inflamed inner ears and in gerbils whose cochlea had lost blood flow for 15 minutes. Eleven people deafened by New Year's Eve firecrackers in Berlin and Munich became the first humans treated. A phase 2 trial of about 210 patients with sudden hearing loss then failed overall because mild cases recovered well on their own, but at 0.4 mg/mL it helped patients whose loss was severe or profound. The phase 3 HEALOS trial in 256 patients repeated the pattern: no benefit in the whole group, a post-hoc signal in profound loss. A second phase 3 trial, ASSENT, was stopped early.
Under the name XG-102 the company Xigen took the same peptide to the eye. Given once under the conjunctiva at the end of complex eye operations, it controlled inflammation about as well as four weeks of dexamethasone drops, although more patients on the lower dose needed rescue treatment. An earlier safety study in 20 patients with post-surgical or traumatic eye inflammation found it barely reached the blood. Two larger phase 3 trials after cataract surgery were completed in 2015 and 2016; we found no published results for them.
In animals the peptide has been tried against a long list of conditions in which JNK is active: stroke, where a single dose into a vein six hours after the blockage shrank infarcts in mice; colitis; Alzheimer-type pathology in transgenic mice; and dying cerebellar neurons. Not every model agreed. In spontaneously hypertensive rats, a strain that resembles older stroke patients more closely, it did not reduce brain damage at all. A 2024 review describes an early bladder trial, under the code KU002, in interstitial cystitis.
Brimapitide is a hospital and clinic drug, never sold or prescribed. Every dose given to people so far was placed by a specialist: through the eardrum, under the lining of the eye, or into a vein during a monitored phase 1 study. Its doses are given below only as what the trials used.
Mechanism of Action
Brimapitide stops JNK from reaching the proteins it normally switches on, so the kinase is present but cannot pass on the stress signal; the TAT segment gets it into cells and the D-amino acids keep it intact.
Blocks JNK's docking site
Its design paper linked the 20-amino-acid JNK-inhibiting domain of IB1 (JIP1) to TAT; the peptide stops JNK reaching targets such as c-Jun, and in treated colitis tissue c-Jun activation fell (PMID 22427801).
Carried into cells by TAT
The arginine-rich HIV TAT sequence lets the peptide cross cell membranes quickly, by active and passive routes, which is why a gel on the round window reaches the cochlea (PMID 29573879).
Strongest where injury is worst
The phase 3 authors propose that JNK switches on only after severe cochlear injury, which would explain why benefit appeared in profound but not milder hearing loss (PMID 31083077).
Published Research
The studies behind brimapitide, read from their PubMed abstracts: the hearing-loss and eye trials, the phase 1 study in healthy volunteers, two reviews, and the animal and tissue studies in the ear, brain and gut. Two are carded because their abstracts name the drug although their titles do not.
Phase 3 HEALOS in sudden deafness
In 256 adults seen within 72 hours of severe to profound one-sided sudden hearing loss, a single injection through the eardrum (0.4 or 0.8 mg/mL) did not improve hearing at day 28 more than placebo in the whole group. A post-hoc analysis found a clinically relevant effect of the 0.4 mg/mL dose in profound loss; drug and procedure were well tolerated.
Phase 2 in acute hearing loss
About 210 patients with acoustic trauma or sudden hearing loss received 0.4 or 2.0 mg/mL or placebo by intratympanic injection within 48 hours. Strong spontaneous recovery of milder cases sank the overall result, but with thresholds of 60 dB or worse the 0.4 mg/mL dose improved hearing, speech discrimination and tinnitus remission compared with placebo.
First people treated: firecracker injuries
Eleven patients deafened by fireworks on New Year's Eve 2005/2006 received AM-111 at 0.4 or 2 mg/mL through the eardrum within 24 hours. The authors judged, from an expected recovery curve rather than a control group, that it seemed to help; 13 adverse events occurred in five people, none serious.
Eye surgery: one injection against drops
In 145 patients after complex eye surgery, one subconjunctival injection of 90 or 900 µg was non-inferior to four weeks of dexamethasone drops for inflammation in the front of the eye at day 28. Rescue treatment was needed by 21% and 15% on the two doses against 4% on dexamethasone; adverse events were similar.
First eye safety study
Twenty patients with inflammation after eye surgery or injury received one subconjunctival dose of 45 to 900 µg. There were 17 non-serious adverse events judged unrelated; inflammation fell from 24 hours and no one needed steroids. The peptide was undetectable in blood except at 900 µg.
Phase 1 infusion in healthy men
Eighteen men received 10, 40 or 80 µg/kg (six placebo) as a one-hour intravenous infusion. Adverse events were mild to moderate and not dose-related; half-life was 0.36-0.65 hours, and exposure rose more than in proportion to the dose.
Bladder pain syndrome (KU002)
A review reports that in a phase 1/2a trial, brimapitide instilled into the bladder acted locally with minimal blood exposure, was well tolerated, and appeared to reduce pain and other symptoms of interstitial cystitis; the trial was exploratory.
Inner-ear uses reviewed
A review of D-JNKI-1 (AM-111) in acute cochlear injury describes its preventive and treatment effects in animal models, its local delivery to the inner ear, and its rapid passage across cell membranes by active and passive routes.
Cochlea starved of blood (gerbils)
After 15 minutes of cochlear ischaemia, AM-111 gel on the round window at 100 µM held the hearing threshold shift at 8 kHz to 3.3 dB against 25 dB in controls and limited inner hair cell loss; 1 and 10 µM worked less well.
Inflamed inner ear (guinea pigs)
In an immune labyrinthitis model, 100 µM AM-111 in gel over the round window within an hour cut hearing loss at day 21 to 39 dB against 68 dB in untreated ears, with better hair cell survival and fewer inflammatory cells; lower concentrations did not differ from controls.
Stroke: a late dose into the vein (mice)
Given intravenously six hours after a 30-minute artery blockage, XG-102 reduced infarct volume from 62 to 18 mm3 at the lowest effective dose and improved behaviour; it still protected when the clot drug rtPA, which worsened damage, was also given.
Stroke: no protection in hypertensive rats
In spontaneously hypertensive rats after 90 minutes of artery blockage, the peptide given into a vein 10 minutes, 1 hour or 2 hours after reperfusion did not reduce infarct volume or improve function at 48 hours, unlike results in other models.
Alzheimer model in transgenic mice
Intravenous brimapitide at 10 mg/kg every three weeks lowered cortical plaque burden after three months; after six months plaques no longer differed, but memory deficits, cell death markers and the inflammatory cytokine IL-1β were reduced.
Lower doses in the same model
Over six months in the same transgenic model, 0.3 mg/kg improved cognition and reduced neuron loss, while only 3 mg/kg also lowered amyloid and synaptic loss, so protection of neurons and effects on plaques separated by dose.
Chemically induced colitis (mice)
One subcutaneous dose of 100 µg/kg, given with the chemical irritant that induced the colitis, reduced weight loss, bleeding, ulceration, immune cell infiltration and TNF-α, and matched or beat daily oral sulfasalazine over 72 hours.
Purkinje cells in brain slices
In cerebellar slice cultures from Lurcher mutant mice, whose Purkinje cells die from a leaky glutamate receptor channel, D-JNKI1 raised surviving Purkinje cells 3.6-fold at 14 days without affecting normal slices.
Dosing Data
Every human dose of brimapitide was given by a specialist inside a trial. The amounts below are what those trials used; there is no approved dose and no form for use outside a clinic.
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 regulator's label that says in what form Brimapitide is supplied. It is prepared and given by clinical staff, not bought and mixed at home: the next part says where.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Brimapitide is prepared and given by clinical staff, by an ear or eye specialist, or in a phase 1 unit.
In every trial carded here it was placed by clinicians: one injection through the eardrum for hearing loss, one injection under the conjunctiva at the end of eye surgery, or a monitored infusion into a vein in healthy volunteers.
Source: PMID 31083077 and PMID 27810317 and PMID 25505576 (studies carded under Research below).
Storage before and after mixing
Unknown: no label on file says how Brimapitide is stored. It is kept and prepared by the hospital or clinic that gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intratympanic injection (through the eardrum) (Single injection; Study: sudden deafness, phase 3 (HEALOS)); Subconjunctival injection (Single injection; Study: inflammation after eye surgery); Intravenous infusion (Single 60-minute infusion; Study: healthy volunteers, phase 1).
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: a half-life of 0.36-0.65 hours (geometric means) after a 60-minute intravenous infusion in healthy men. After about five half-lives almost none is left.
How long the doses were given: Study: sudden deafness, phase 3 (HEALOS): Once, within 72 hours of onset; Study: acute hearing loss, phase 2: Once, within 48 hours of onset; Study: inflammation after eye surgery: Once, at the end of surgery.
When effects appear: unknown; no source on this page gives a time to effect for Brimapitide. Results reported in the studies are under Published Research.
Source: half-life: PMID 25505576; 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: The drug and the injection through the eardrum were well tolerated in both hearing-loss trials (PMIDs 24979398, 31083077); In the first ear study, 13 adverse events in five of 11 patients, none serious or severe (PMID 17712672); After eye surgery, adverse events were similar to dexamethasone drops, but more patients needed rescue treatment for inflammation (PMID 27810317); After an infusion in healthy men: mild to moderate events; headache and fatigue were the only ones judged possibly related (PMID 25505576). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Brimapitide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Brimapitide (reviewed 2026-10-30) 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 Brimapitide 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 Brimapitide's expected mass, 3,822.5 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved (Not approved: Drugs@FDA (openFDA) holds no application for brimapitide, AM-111 or XG-102, and the EMA medicines list no entry (searched October 30, 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 trials above. No serious adverse event in them was attributed to the drug.
Contraindications & Cautions
There is no label. These cautions follow from how and where it was tested.
Legal Status
Brimapitide is an investigational drug. It has no marketing approval in any country checked.
Frequently Asked Questions
?What is brimapitide?
A synthetic peptide of 31 D-amino acids that blocks the stress enzyme JNK inside cells. It was developed as AM-111 for sudden hearing loss and as XG-102 for eye inflammation.
?Does it restore hearing after sudden deafness?
Not in the trials as a whole. Both the phase 2 and the phase 3 trial missed their main goal; the benefit appeared only in patients with severe or profound loss, found partly by post-hoc analysis.
?How is it given?
In the ear trials, as one injection of gel through the eardrum. In the eye trials, as one injection under the conjunctiva at the end of surgery. A phase 1 study gave it as a one-hour infusion into a vein.
?Why is it made of D-amino acids?
The body's protein-cutting enzymes are built for L-amino acids. A chain made in the mirror form and in reverse order keeps the shape of the active site while resisting digestion.
?Is it the same as AM-111 and XG-102?
Yes. AM-111, XG-102 and D-JNKI-1 are names for the same peptide used by different developers; the trial abstracts give brimapitide as its official name.
?Can I buy it?
No. It is not approved anywhere and was only ever given by clinicians inside trials.
References
- [clinical-trial] Staecker H, et al. "Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study." Otol Neurotol, 2019;40(5):584-594. PMID: 31083077.
- [clinical-trial] Suckfuell M, et al. "Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: a double-blind, randomized, placebo-controlled phase II study." Otol Neurotol, 2014;35(8):1317-26. PMID: 24979398.
- [clinical-trial] Suckfuell M, et al. "Intratympanic treatment of acute acoustic trauma with a cell-permeable JNK ligand: a prospective randomized phase I/II study." Acta Otolaryngol, 2007;127(9):938-42. PMID: 17712672.
- [clinical-trial] Chiquet C, et al. "Postoperative Ocular Inflammation: A Single Subconjunctival Injection of XG-102 Compared to Dexamethasone Drops in a Randomized Trial." Am J Ophthalmol, 2017;174:76-84. PMID: 27810317.
- [clinical-trial] Beydoun T, et al. "Subconjunctival injection of XG-102, a JNK inhibitor peptide, in patients with intraocular inflammation: a safety and tolerability study." J Ocul Pharmacol Ther, 2015;31(2):93-9. PMID: 25347151.
- [clinical-trial] Deloche C, et al. "XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind, placebo-controlled, dose-escalating study." Pharmacol Res Perspect, 2014;2(1):e00020. PMID: 25505576.
- [review] Taubert E, et al. "Bladder pain syndrome AKA interstitial cystitis - a condition with severe unmet medical need: an exploration of brimapitide as a potential treatment opportunity." Curr Opin Urol, 2024;34(2):52-57. PMID: 37975427.
- [review] Eshraghi AA, et al. "Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111)." Hear Res, 2018;368:86-91. PMID: 29573879.
- [pubmed] Omotehara Y, et al. "Protection against ischemic cochlear damage by intratympanic administration of AM-111." Otol Neurotol, 2011;32(9):1422-7. PMID: 22089955.
- [pubmed] Barkdull GC, et al. "AM-111 reduces hearing loss in a guinea pig model of acute labyrinthitis." Laryngoscope, 2007;117(12):2174-82. PMID: 18322422.
- [pubmed] Wiegler K, et al. "The JNK inhibitor XG-102 protects from ischemic damage with delayed intravenous administration also in the presence of recombinant tissue plasminogen activator." Cerebrovasc Dis, 2008;26(4):360-6. PMID: 18728363.
- [pubmed] Gow WR, et al. "Lack of neuroprotection of inhibitory peptides targeting Jun/JNK after transient focal cerebral ischemia in spontaneously hypertensive rats." J Cereb Blood Flow Metab, 2011;31(12):e1-8. PMID: 21971350.
- [pubmed] Gourmaud S, et al. "Brimapitide Reduced Neuronal Stress Markers and Cognitive Deficits in 5XFAD Transgenic Mice." J Alzheimers Dis, 2018;63(2):665-674. PMID: 29660941.
- [pubmed] Porte B, et al. "Dose-dependent neuroprotective effect of the JNK inhibitor Brimapitide in 5xFAD transgenic mice." Brain Res, 2020;1727:146587. PMID: 31811838.
- [pubmed] Reinecke K, et al. "The JNK inhibitor XG-102 protects against TNBS-induced colitis." PLoS One, 2012;7(3):e30985. PMID: 22427801.
- [pubmed] Repici M, et al. "Specific JNK inhibition by D-JNKI1 protects Purkinje cells from cell death in Lurcher mutant mouse." Cerebellum, 2008;7(4):534-8. PMID: 18949529.
- [pubmed] Bonny C, et al. "Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death." Diabetes, 2001;50(1):77-82. PMID: 11147798.
- [pubmed] Borsello T, et al. "A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia." Nat Med, 2003;9(9):1180-6. PMID: 12937412.
- [registry] ClinicalTrials.gov API v2, read October 30, 2026: NCT02561091 (HEALOS, phase 3, AM-111 in acute inner ear hearing loss, 256 enrolled, completed September 2017); NCT02809118 (ASSENT, phase 3, terminated February 2018: 'Availability of relevant new efficacy data from another study'); NCT00802425 (phase 2, 210, completed); NCT02235272 and NCT02508337 (phase 3, XG-102 in post-cataract surgery intraocular inflammation, 339 and 309 enrolled, completed 2015 and 2016); NCT01570205 (phase 1, single IV infusion of 10, 40 and 80 µg/kg, completed). https://clinicaltrials.gov/study/NCT02561091
- [other] ChEMBL CHEMBL4297650 (brimapitide, synonym XG-102): structure of 31 D-amino acids with a C-terminal glycinamide, full molecular formula C164H286N66O40, molecular weight 3822.51. Read October 30, 2026. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL4297650/
- [other] US FDA, Drugs@FDA (openFDA drugsfda endpoint), searched October 30, 2026: no application for brimapitide, AM-111 or XG-102.
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Trial registrations come from ClinicalTrials.gov and regulatory status from Drugs@FDA and the EMA medicines list, read the same day; structure and formula from ChEMBL. 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.