Murabutide
A tamed version of the bacterial cell-wall fragment that wakes up innate immunity, tried as a vaccine adjuvant and as an add-on treatment in HIV
Murabutide is a synthetic relative of muramyl dipeptide, the smallest piece of bacterial cell wall that the immune system recognises. Chemists changed the dipeptide's end so that it kept the immune-boosting effect but lost the fever and inflammation that made muramyl dipeptide unusable in people. It activates the NOD2 sensor inside immune cells, boosted antibody responses to vaccines in animals and suppressed HIV in cultured cells. Small French trials published between 2001 and 2003 gave it to people with HIV and to healthy volunteers. It was never approved and no trial is registered today.
Used in human trials: 7 mg, Once daily, 5 days a week, Not stated in the abstract (Study: six-week cycle in HIV with failing antiretroviral therapy) 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?
In the 1970s researchers found that the immune-boosting power of Freund's complete adjuvant, a mixture of oil and killed mycobacteria, came largely from one small piece of the bacterial cell wall: muramyl dipeptide (MDP), a sugar joined to two amino acids. MDP was a potent adjuvant, but its inflammatory side effects kept it out of human use. Murabutide was one of many attempts to keep the benefit and lose the harm: its isoglutamine is swapped for glutamine with a butyl ester, and a 1984 mouse study described it as free of MDP's side effects while it raised antibody responses to hepatitis B surface antigen as well as alum did.
Later work explained what murabutide does. Like MDP it is sensed by NOD2, a receptor inside macrophages, dendritic cells and other immune cells. In human whole blood it switched on several inflammatory messengers, including tumour necrosis factor, IL-1 beta, IL-6 and IL-8, along with the calming IL-1 receptor antagonist, but not interferon gamma or IL-12. It matured dendritic cells, changed the activity of dozens of genes in human macrophages, and strengthened the effects of interferon-alpha and interleukin-2 against tumours and inflammation in mice. In mouse vaccine studies it worked as an injected and an intranasal adjuvant.
Its most distinctive finding came from HIV research. In human macrophages and dendritic cells infected in the laboratory, murabutide sharply cut virus production by acting after the virus entered the cell, without stopping cell division. That led to clinical work by a French group. A single dose of 5, 7 or 9 mg was well tolerated in people with HIV on antiretroviral drugs, with blood cytokines peaking at about 7 mg; five daily doses of 7 mg were also tolerated. Six-week cycles of 7 mg on five days a week were then given to untreated patients with good CD4 counts and, in a randomised trial of 42 people, to patients whose long-term antiretroviral treatment was failing. Some immune measures improved and, in the randomised trial, more patients reached an undetectable viral load, but reversible grade III adverse events occurred and the trials were small.
A healthy-volunteer study showed that giving murabutide with interferon-alpha did not add to interferon's side effects and produced a mostly anti-inflammatory cytokine pattern. Work on murabutide continued in animals, as an adjuvant for anthrax and norovirus-like particle vaccines and as a radiation protector in mice, but no larger trial followed the HIV studies. ChEMBL lists phase 2 as its furthest stage, and searches of ClinicalTrials.gov, Drugs@FDA and the EMA list return nothing.
Murabutide is therefore an investigational immunomodulator with small, positive-leaning phase 1/2 studies that were never confirmed. Its relatives went further: mifamurtide, a lipid-linked muramyl tripeptide, is approved in Europe for osteosarcoma. The amounts below are what the HIV trials gave; they describe research, not a treatment anyone can obtain.
Mechanism of Action
Murabutide is a synthetic muramyl dipeptide derivative that activates NOD2, an innate immune sensor inside macrophages, dendritic cells and other cells, designed to avoid the inflammatory side effects of its parent.
NOD2 activation
Recognised by NOD2, the cell's sensor for bacterial peptidoglycan fragments, which drives innate immune signalling (PMID 23531213).
Selective cytokines
Induces tumour necrosis factor, IL-1 beta, IL-6, IL-8 and IL-1 receptor antagonist in human blood, but not interferon gamma or IL-12 (PMID 8894442).
Dendritic cell maturation
Raises antigen-presenting and co-stimulatory molecules and T-cell stimulation, the basis of its adjuvant effect (PMID 11529939).
Blocks HIV after entry
In infected macrophages and dendritic cells it suppressed nuclear viral DNA and viral RNA without blocking entry or reverse transcription (PMID 10933686).
Published Research
Studies of murabutide read from their PubMed abstracts: the four clinical studies in HIV and healthy volunteers, laboratory work on human immune cells and HIV, animal vaccine, infection, tumour and radiation studies, a structural study and two reviews. One 2003 review has no abstract and is listed under References only.
First doses in people with HIV
Two phase 1/2 studies in HIV-positive patients on antiretroviral therapy. Single doses of 5, 7 or 9 mg, six patients each, were well tolerated and raised selected serum cytokines and chemokines, levelling off at 7 mg. Then 12 patients received 7 mg on five consecutive days, again well tolerated, with lower HIV co-receptor levels on lymphocytes and better lymphocyte responses for up to three weeks.
Randomised trial in failing HIV treatment
Forty-two patients with poor immune recovery and detectable virus despite long-term combination therapy were randomised to 7 mg a day on five days a week for six weeks, or no murabutide. Treated patients alone showed rises in CD4 cells, platelets and the share with undetectable virus a week later, and only the last differed significantly between groups. Some reversible grade III adverse events occurred.
Untreated HIV, six-week cycle
Nine patients not yet on antiretroviral drugs, with CD4 counts above 500 and modest viral loads, received 7 mg daily on five days a week for six weeks and were followed for 22 weeks. Viral load and clinical status stayed stable, two reversible grade III events occurred, and lymphocyte responses and naive T-cell percentages improved compared with nine untreated patients followed the same way.
With interferon-alpha in healthy volunteers
Healthy volunteers received murabutide together with increasing doses of interferon-alpha. Side effects matched those of interferon-alpha alone, with no added toxicity, and the cytokines that rose were mainly anti-inflammatory ones and HIV-blocking chemokines rather than key inflammatory cytokines. Because interferon was given too, the tolerability finding is for the pair.
Blocks HIV in macrophages and dendritic cells
In human monocyte-derived macrophages and dendritic cells infected with HIV-1, murabutide strongly suppressed virus replication. Entry, reverse transcription and early viral DNA were unaffected, but nuclear viral DNA forms and viral RNA fell sharply; the cells showed less CD4 and CCR5 and released more beta-chemokines, which did not explain the effect.
Matures dendritic cells
Immature human dendritic cells treated with murabutide raised HLA-DR, CD80, CD86, CD40 and CD83, took up less material, stimulated T cells more strongly and became more cytostatic to a tumour cell line. They briefly released more MIP-1 beta, tumour necrosis factor and IL-10 and steadily more M-CSF, and all three MAPK families were activated.
Selective cytokines in human blood
In human whole blood, murabutide quickly induced tumour necrosis factor, IL-1 beta, IL-6, IL-8 and the IL-1 receptor antagonist, but not IL-4, IL-12, interferon gamma or colony-stimulating factors. IL-3 and granulocyte-macrophage colony-stimulating factor amplified its IL-8 and IL-1 receptor antagonist responses.
Gene response of human macrophages
Microarrays covering 1,081 genes in macrophages from four donors showed that six hours of murabutide raised 40 genes and lowered 16, spanning immune mediators and their receptors, transcription factors, kinases, matrix proteins, ion channels and metabolic enzymes.
Shape compared with muramyl dipeptide
Two-dimensional proton NMR suggested that muramyl dipeptide folds into two successive beta-turns, while murabutide keeps only the first, the turn involving the sugar and alanine.
Adjuvant for hepatitis B antigen
Given in saline with natural hepatitis B surface antigen, murabutide raised antibody responses in mice as well as alum, with lower IgE, and the two together acted synergistically. With a synthetic antigen fragment linked to a toxoid carrier, it produced high levels of antibodies to the peptide.
Protects mice against influenza
In young mice infected with a lethal dose of influenza A virus, murabutide given under the skin or into the nose had protective and therapeutic effects when started up to four days before or two days after infection, depending on route and dose.
Combined with interferon in mice
Murabutide and type I interferon each protected mice against concanavalin A hepatitis, and together they lowered liver enzymes more. The combination also caused regression of MethA sarcomas, leaving almost half of the mice tumour-free.
Intranasal vaccine adjuvant
Given with Norwalk virus-like particles into the nose of mice, murabutide raised virus-specific IgG in blood and IgA at distant mucosal sites, with 100 micrograms the best dose in mice. It matched cholera toxin and another adjuvant and beat injected alum for mucosal responses.
Anthrax vaccine adjuvant
In mice given anthrax protective antigen, murabutide alone was a weaker adjuvant than the polysaccharide Advax, but the two together gave complete protection against inhaled anthrax after two doses, lasting memory to 18 months and about a third of alum's local inflammation.
Radiation protection in mice
Pretreatment with murabutide protected cultured cells and mice from radiation injury and reduced radiation-induced cell death. The effect depended on the ATR DNA-damage-repair pathway: blocking ATR removed it, while blocking the related repair kinase did not.
Murabutide revisited
This review describes murabutide as a safe NOD2-activating derivative of muramyl dipeptide, summarises its adjuvant, anti-infective, antitumour and blood-forming effects in cells and animals, and reviews clinical studies in which it worked with therapeutic cytokines and in chronic viral disease.
Muramyl peptides in clinical development
This overview reports that MDP and its derivatives did not directly inflame cultured human vein endothelial cells, compares the cytokines that candidate muramyl peptides induce in human blood, and describes the selective, non-toxic synergy of murabutide with interferon-alpha in the laboratory and in people.
Dosing Data
These are the amounts given in the published clinical studies, all French and published between 2002 and 2003. Murabutide was never approved, and the abstracts do not state the route of administration.
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 Murabutide 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: not stated in the abstract). 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 Murabutide, 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 Murabutide stays intact once mixed.
How it is taken
As it was given in human studies: Not stated in the abstract (Once daily, 5 days a week; Study: six-week cycle in HIV with failing antiretroviral therapy).
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: six-week cycle in HIV with failing antiretroviral therapy: 6 weeks, added to antiretroviral therapy; Study: six-week cycle in untreated HIV: 6 weeks; Study: single and repeated doses in HIV: One day; then 5 consecutive days.
When effects appear: unknown; no source on this page gives a time to effect for Murabutide. 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: Generally well tolerated at single doses of 5 to 9 mg and five daily doses of 7 mg (PMID 12131566); Reversible grade III adverse events during six-week cycles, which resolved when treatment stopped (PMIDs 12716777, 12824957); With interferon-alpha, side effects matched interferon alone, with no added toxicity (PMID 11576459). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Murabutide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the clinical studies above, all small and short”).
Interactions
- interferon-alpha: given together to healthy volunteers with increasing interferon-alpha doses, the combination was well tolerated, with side effects similar to interferon-alpha alone
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 11576459.
Checking what you bought
Unknown: no published independent test of Murabutide 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 Murabutide's expected mass, 548.6 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 anywhere we found: 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 clinical studies above, all small and short.
Contraindications & Cautions
Murabutide is not an approved medicine anywhere, so it has no label.
Legal Status
Murabutide reached phase 2 and was never approved.
Frequently Asked Questions
?What is murabutide?
A synthetic derivative of muramyl dipeptide, the smallest piece of bacterial cell wall the immune system recognises. It activates the NOD2 sensor in immune cells.
?How is it different from muramyl dipeptide?
It replaces isoglutamine with a butyl-esterified glutamine. That kept the adjuvant effect while, in the studies here, dropping the inflammatory side effects that kept muramyl dipeptide out of human use.
?Did it work against HIV?
It suppressed HIV in cultured cells. In small trials it was tolerated and improved some immune measures, and in one randomised trial more patients reached undetectable virus, but no larger trial confirmed this.
?Is it approved anywhere?
No. It reached phase 2 and stopped there. Drugs@FDA, the EMA list and ClinicalTrials.gov have no record of it.
?Is it the same as mifamurtide?
No. Mifamurtide is a different muramyl peptide, a lipid-linked tripeptide given in liposomes, and it is approved in Europe for osteosarcoma. Murabutide is a water-soluble dipeptide ester.
?Is it used in vaccines?
Only experimentally. It boosted responses to hepatitis B, anthrax and norovirus-like particle antigens in mice, but no approved vaccine contains it.
References
- [clinical-trial] Amiel C, et al. "Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator murabutide in HIV-1-infected patients." J Acquir Immune Defic Syndr, 2002;30(3):294-305. PMID: 12131566.
- [clinical-trial] Bahr GM, et al. "Clinical and immunological effects of a 6 week immunotherapy cycle with murabutide in HIV-1 patients with unsuccessful long-term antiretroviral treatment." J Antimicrob Chemother, 2003;51(6):1377-88. PMID: 12716777.
- [clinical-trial] De La Tribonniere X, et al. "A phase I study of a six-week cycle of immunotherapy with Murabutide in HIV-1 patients naive to antiretrovirals." Med Sci Monit, 2003;9(6):PI43-50. PMID: 12824957.
- [clinical-trial] Darcissac EC, et al. "Clinical tolerance and profile of cytokine induction in healthy volunteers following the simultaneous administration of ifn-alpha and the synthetic immunomodulator murabutide." J Interferon Cytokine Res, 2001;21(9):655-61. PMID: 11576459.
- [pubmed] Darcissac EC, et al. "The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells." J Virol, 2000;74(17):7794-802. PMID: 10933686.
- [pubmed] Vidal V, et al. "Enhanced maturation and functional capacity of monocyte-derived immature dendritic cells by the synthetic immunomodulator Murabutide." Immunology, 2001;103(4):479-87. PMID: 11529939.
- [pubmed] Darcissac EC, et al. "Selective potentiation of cytokine expression in human whole blood by murabutide, a muramyl dipeptide analogue." Cytokine, 1996;8(8):658-66. PMID: 8894442.
- [pubmed] Goasduff T, et al. "The transcriptional response of human macrophages to murabutide reflects a spectrum of biological effects for the synthetic immunomodulator." Clin Exp Immunol, 2002;128(3):474-82. PMID: 12067302.
- [pubmed] Fermandjian S, et al. "A comparative 1H-n.m.r. study of MurNAc-L-Ala-D-iGln (MDP) and its analogue murabutide: evidence for a structure involving two successive beta-turns in MDP." Carbohydr Res, 1987;162(1):23-32. PMID: 3594477.
- [pubmed] Audibert FM, et al. "Enhancement by murabutide of the immune response to natural and synthetic hepatitis B surface antigens." Infect Immun, 1984;45(1):261-6. PMID: 6735468.
- [pubmed] Chomel JJ, et al. "Prophylactic and therapeutic effects of murabutide in OF1 mice infected with influenza A/H3N2 (A/Texas/1/77) virus." J Biol Response Mod, 1988;7(6):581-6. PMID: 2851033.
- [pubmed] Bahr GM, et al. "Enhancement in vivo of the antiinflammatory and antitumor activities of type I interferon by association with the synthetic immunomodulator murabutide." J Interferon Cytokine Res, 1996;16(4):297-306. PMID: 9162523.
- [pubmed] Jackson EM, et al. "Intranasal vaccination with murabutide enhances humoral and mucosal immune responses to a virus-like particle vaccine." PLoS One, 2012;7(7):e41529. PMID: 22855691.
- [pubmed] Feinen B, et al. "Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant." Clin Vaccine Immunol, 2014;21(4):580-6. PMID: 24554695.
- [pubmed] Liu L, et al. "NOD2 agonist murabutide alleviates radiation-induced injury through DNA damage response pathway mediated by ATR." J Cell Physiol, 2019;234(11):21294-21306. PMID: 31054162.
- [review] Jakopin Ž. "Murabutide revisited: a review of its pleiotropic biological effects." Curr Med Chem, 2013;20(16):2068-79. PMID: 23531213.
- [review] Bahr GM, et al. "Immunopharmacological activities and clinical development of muramyl peptides with particular emphasis on murabutide." Int J Immunopharmacol, 1995;17(2):117-31. PMID: 7544767.
- [review] Bahr GM. "Non-specific immunotherapy of HIV-1 infection: potential use of the synthetic immunodulator murabutide." J Antimicrob Chemother, 2003;51(1):5-8. PMID: 12493780.
- [other] PubChem CID 91617595, Murabutide: formula C23H40N4O11, molecular weight 548.6. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/91617595
- [other] ChEMBL CHEMBL1908312, murabutide: maximum clinical phase 2 in the ChEMBL molecule record, read October 2, 2026 (the Registry's ChEMBL harvest). https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1908312/
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Formula and weight from PubChem; development stage from ChEMBL; status from Drugs@FDA, the EMA medicines list and ClinicalTrials.gov, searched October 28, 2026. 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.