Muramyl Dipeptide
The bacterial fragment the immune system's NOD2 sensor recognises, why it matters in Crohn's disease, and how it differs from the drugs built on it
Muramyl dipeptide (MDP) is a sugar joined to two amino acids, the smallest part of the bacterial cell wall that still stirs the immune system. Almost all bacteria carry it. Inside our cells it is recognised by NOD2, and the NOD2 variants that raise the risk of Crohn's disease are the ones that fail to recognise it. In animals it causes fever and sleepiness and, in mice, protected against influenza. MDP itself has never been given to people as a treatment; its derivatives, such as mifamurtide and murabutide, are different molecules.
No established human dose Details ↓
Recommended Dosing
No established human dose
Muramyl dipeptide has not been given to people in any study read. The human evidence is laboratory work on blood, gut and immune cells from donors and patients, and one study that measured MDP already circulating in elderly people's plasma.
What is it?
Bacteria are wrapped in a mesh called peptidoglycan, made of sugar chains cross-linked by short peptides. Muramyl dipeptide is the smallest piece of that mesh that still has a strong effect on the immune system: the sugar N-acetylmuramic acid attached to two amino acids, L-alanine and D-isoglutamine. It occurs in most Gram-negative and Gram-positive bacteria, and chemists have made many derivatives of it to use as immune boosters.
In 2003 two groups showed which receptor senses it. NOD2, a protein inside immune and gut-lining cells, responded to MDP but not to the near-identical molecules in which either amino acid was swapped for its mirror image, and the Toll-like receptor TLR2 did not respond. The NOD2 variants linked to Crohn's disease, above all a frameshift mutation, could not detect MDP, and blood cells from people carrying two copies of that variant responded to bacterial endotoxin but not to MDP. Later work found the binding site in NOD2's leucine-rich repeat region, with both the sugar and the peptide part of MDP contributing.
That made MDP a central tool in Crohn's disease research. In blood cells from healthy donors, MDP on its own triggered interleukin-8 but little TNF-α, and it strongly boosted the response to Toll-like receptor signals; the common Crohn's double-mutant genotypes lost both effects, which suggested a test of NOD2 function. Dendritic cells from Crohn's patients with NOD2 mutations failed to switch on pathogen-response genes when given MDP. In the gut, the peptide transporter hPepT1 carries MDP into colon cells, where it sets off inflammatory signalling, and normal stool and caecal contents held micromolar amounts. A 2013 review traces how MDP signalling, through NOD2 and other routes, shapes the gut inflammation of Crohn's disease.
MDP's effects reach beyond NOD2. In mouse macrophages it is taken up into acidic vesicles and, when the pore protein pannexin-1 opens, released into the cell's interior, where it drives caspase-1 activation through the NLRP3 inflammasome independently of NOD2. In human endothelial cells from the eye it raised interleukin-6 release, a finding relevant to Blau syndrome, another disease caused by NOD2 mutations.
In animals MDP is a pyrogen and a sleep-inducing substance. Injected into rabbits it suppressed REM sleep and raised body temperature in a time-of-day-dependent way, a single injection made squirrel monkeys spend much less of their day alert, and repeated injections gave guinea pigs fever with rising TNF-α and interleukin-6. In mice, MDP reduced deaths and viral load after influenza infection by recruiting monocytes to the lungs through NOD2, and weekly injections slowed memory decline in a mouse model of Alzheimer's disease.
In people, the only measurements here are of MDP produced by bacteria: plasma MDP in 135 frail elderly people was linked to lower levels of the anti-inflammatory cytokine interleukin-10. MDP itself has not been developed as a medicine, and in animals it causes fever. Its derivatives went to the clinic instead: mifamurtide, a muramyl tripeptide joined to a lipid and packed in liposomes, is authorised in the EU for osteosarcoma and has its own entry; murabutide, a safer derivative studied as an adjuvant, also has its own entry; and muroctasin was tried after lymphoma chemotherapy (see References). Their results are theirs, not MDP's. ChEMBL lists a maximum clinical phase of 1 for MDP, but no study read gave it to people.
Mechanism of Action
Muramyl dipeptide is a bacterial fragment that the body senses, not a hormone it makes. Inside cells, the receptor NOD2 recognises it and switches on inflammatory signalling.
NOD2 sensing
NOD2 binds MDP through its leucine-rich repeat domain and turns on NF-κB, leading to cytokines such as interleukin-8; Crohn's-linked NOD2 variants lose this response.
Priming other alarms
MDP strongly boosts the response of blood cells to Toll-like receptor signals and, through pannexin-1, can activate the NLRP3 inflammasome.
Fever and sleep (animals)
In rabbits, monkeys and guinea pigs it causes fever and changes sleep; in guinea pigs the fever followed rises in TNF-α and interleukin-6.
Published Research
These are studies of muramyl dipeptide itself, read from their PubMed abstracts: the NOD2 discovery papers and Crohn's disease studies on human cells, one measurement in human plasma, mechanism studies, animal studies of fever, sleep, influenza and Alzheimer-type disease, and a review. No study here gave MDP to a person; trials of its derivatives belong to those drugs.
NOD2 recognises MDP; Crohn's variants do not
MDP was the bacterial structure NOD2 needed, and recognition was stereoselective: mirror-image amino-acid versions were inactive. TLR2 did not respond. Crohn's-associated NOD2 mutants failed to recognise MDP, and blood cells from people homozygous for the main frameshift variant responded to endotoxin but not to MDP.
NOD2 is a general sensor of peptidoglycan
A second group showed NOD2 detects peptidoglycan from all bacteria through MDP, the minimal active motif, and that the 3020insC frameshift, the commonest Crohn's variant, abolishes this detection completely.
MDP primes blood cells; Crohn's mutants do not
In human blood mononuclear cells, MDP alone induced strong interleukin-8 but little TNF-α or interleukin-1β, and it greatly amplified cytokine release to Toll-like receptor ligands. The common Crohn's double-mutant NOD2 genotypes abolished these effects at low nanomolar MDP.
Dendritic cells from Crohn's patients
Stimulated with MDP, dendritic cells from wild-type Crohn's patients changed 683 genes, mostly inflammatory, and those from healthy volunteers 50, mostly pathogen-response genes. Cells from patients with two NOD2 mutations did not switch on pathogen-response genes, changing mainly apoptosis-regulation genes instead.
NOD2 mutations blunt the B-cell response
In 294 inflammatory bowel disease patients and 298 controls, three NOD2 mutations were tied to Crohn's disease. NOD2 was expressed in human B cells, and the rise in its expression with MDP stimulation was impaired in cells carrying the mutations.
Where NOD2 grips MDP
A purified leucine-rich repeat domain of NOD2 bound MDP with high affinity (dissociation constant about 212 nM) in surface plasmon resonance tests. Mutations and MDP fragments showed both the peptide and the sugar parts take part in binding.
Carried into colon cells by hPepT1
The gut peptide transporter hPepT1 took up MDP into human colon cells, where it activated NF-κB and interleukin-8 release through NOD2. MDP measured 20 to 87 µmol/L in normal caecal and stool samples and was undetectable in duodenal fluid.
A NOD2-independent route to the inflammasome
In macrophages, MDP was taken up into acidified vesicles regardless of NOD2 and released into the cytosol through pannexin-1 when adenosine triphosphate was added, activating caspase-1 through cryopyrin (NLRP3). Induction of pro-interleukin-1β still needed NOD2.
Eye blood-vessel cells respond to MDP
Endothelial cells of the human uveal tract expressed NOD2, more so after inflammatory cytokines, and choroidal endothelial cells released more interleukin-6 with MDP, synergising with Toll-like receptor ligands, relevant to the eye inflammation of Blau syndrome.
MDP activates human monocytes
Human monocytes exposed to free MDP for 48 hours became better at stopping the growth of a leukaemia cell line, though not at killing it; the effect did not appear to depend on hydrogen peroxide or released factors.
Circulating MDP in the frail elderly
In 135 frail elderly people, plasma MDP, measured with other bacterial products, was not linked to age, sex or illnesses after correction for multiple tests, but higher MDP went with lower interleukin-10, an anti-inflammatory cytokine.
Sleep and fever in rabbits
Injected into the brain ventricles of rabbits, MDP cut REM sleep and, in a warmer room, deepened slow-wave sleep; the mirror-image isomer had no effect. Given intravenously, it raised body temperature more during the light hours than the dark.
Drowsy squirrel monkeys
After a single MDP injection early in their day, squirrel monkeys were alert only 47% of the daytime against 87% after saline, spending more time in transitional and non-REM sleep; REM sleep was suppressed for some hours.
Fever with repeated injections in guinea pigs
MDP injected into muscle caused a two-phase fever preceded by high TNF-α and interleukin-6. With five injections three days apart, the early fever persisted while the late phase weakened.
Protection against influenza in mice
MDP treatment of influenza-infected mice reduced deaths, viral load and lung inflammation through NOD2, by transiently recruiting inflammatory monocytes to the lungs; a mycobacterial form, N-glycolyl MDP, cut viral load further.
Slower decline in Alzheimer model mice
Weekly MDP for three months in APPswe/PS1 mice delayed cognitive decline in both sexes and protected the blood-brain barrier; males had less amyloid in the brain, while in females microglia surrounded plaques.
MDP pathways in Crohn's disease
The review explains that MDP, found in most Gram-negative and Gram-positive bacteria, triggers immune responses in the gut and that changes in NOD2 and other parts of the MDP response are linked to Crohn's disease, making the normalisation of MDP signalling a possible treatment target.
No Established Human Dose
Muramyl dipeptide has not been given to people in any study read. The human evidence is laboratory work on blood, gut and immune cells from donors and patients, and one study that measured MDP already circulating in elderly people's plasma. The derivatives that did reach people, such as mifamurtide, murabutide and muroctasin, are different molecules, so their doses cannot stand in for one.
What this rests on: PMID 12514169, PMID 15910952, PMID 25278013.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, 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 Muramyl Dipeptide is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Muramyl Dipeptide has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Muramyl Dipeptide, 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 Muramyl Dipeptide stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Muramyl Dipeptide. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Muramyl Dipeptide lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: Raised body temperature in rabbits, and fever with rises in TNF-α and interleukin-6 in guinea pigs (PMIDs 3394839, 9242715); Sleepiness and suppressed REM sleep in squirrel monkeys and rabbits (PMIDs 6496716, 3394839); Strong inflammatory signalling in human immune and gut cells in the laboratory (PMIDs 15910952, 15521010). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Muramyl Dipeptide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“No human safety data exist for MDP itself”).
Interactions
Unknown: a PubMed search for human interaction studies of Muramyl Dipeptide (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 Muramyl Dipeptide 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 Muramyl Dipeptide's expected mass, 492.5 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved: Drugs@FDA and the EMA medicines list hold no record for muramyl dipeptide itself (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
No human safety data exist for MDP itself. In animals it has clear effects.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Muramyl dipeptide is a research chemical; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is muramyl dipeptide?
The smallest part of the bacterial cell wall that still activates the immune system: the sugar N-acetylmuramic acid joined to L-alanine and D-isoglutamine.
?How does the body detect it?
Through NOD2, a sensor inside immune and gut-lining cells. NOD2 binds MDP and switches on inflammatory signalling.
?What does it have to do with Crohn's disease?
The NOD2 variants that raise the risk of Crohn's disease cannot recognise MDP, and cells from people carrying them respond poorly to it. This made MDP a key tool for studying the disease.
?Has MDP been given to people?
Not in any study read. It causes fever in animals. Its derivatives, such as mifamurtide and murabutide, were given to people, but they are different molecules.
?Is mifamurtide the same as muramyl dipeptide?
No. Mifamurtide is a muramyl tripeptide linked to a lipid and packaged in liposomes, approved in the EU for osteosarcoma. It has its own entry.
?Is MDP found in the body?
Yes, from gut bacteria. It was measured in normal stool and caecal contents and in the plasma of elderly people.
References
- [pubmed] Inohara N, et al. "Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease." J Biol Chem, 2003;278(8):5509-12. PMID: 12514169.
- [pubmed] Girardin SE, et al. "Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection." J Biol Chem, 2003;278(11):8869-72. PMID: 12527755.
- [pubmed] van Heel DA, et al. "Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease." Lancet, 2005;365(9473):1794-6. PMID: 15910952.
- [pubmed] Zelinkova Z, et al. "Muramyl dipeptide-induced differential gene expression in NOD2 mutant and wild-type Crohn's disease patient-derived dendritic cells." Inflamm Bowel Dis, 2008;14(2):186-94. PMID: 17941075.
- [pubmed] Lin Z, et al. "NOD2 mutations affect muramyl dipeptide stimulation of human B lymphocytes and interact with other IBD-associated genes." Dig Dis Sci, 2013;58(9):2599-607. PMID: 23709157.
- [pubmed] Lauro ML, et al. "Molecular Recognition of Muramyl Dipeptide Occurs in the Leucine-rich Repeat Domain of Nod2." ACS Infect Dis, 2017;3(4):264-270. PMID: 27748583.
- [pubmed] Vavricka SR, et al. "hPepT1 transports muramyl dipeptide, activating NF-kappaB and stimulating IL-8 secretion in human colonic Caco2/bbe cells." Gastroenterology, 2004;127(5):1401-9. PMID: 15521010.
- [pubmed] Marina-García N, et al. "Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2." J Immunol, 2008;180(6):4050-7. PMID: 18322214.
- [pubmed] Davey MP, et al. "Human endothelial cells express NOD2/CARD15 and increase IL-6 secretion in response to muramyl dipeptide." Microvasc Res, 2006;71(2):103-7. PMID: 16414084.
- [pubmed] Kildahl-Andersen O, et al. "Activation of human monocytes by free muramyl dipeptide (MDP)." Acta Pathol Microbiol Immunol Scand C, 1984;92(3):181-7. PMID: 6507104.
- [pubmed] Verschoor CP, et al. "Circulating muramyl dipeptide is negatively associated with interleukin-10 in the frail elderly." Inflammation, 2015;38(1):272-7. PMID: 25278013.
- [pubmed] Shoham S, et al. "Muramyl dipeptide-induced sleep and fever: effects of ambient temperature and time of injections." Am J Physiol, 1988;255(1 Pt 2):R157-65. PMID: 3394839.
- [pubmed] Wexler DB, et al. "Effects of a muramyl dipeptide on the temperature and sleep-wake cycles of the squirrel monkey." Am J Physiol, 1984;247(4 Pt 2):R672-80. PMID: 6496716.
- [pubmed] Roth J, et al. "Fever and production of cytokines in response to repeated injections of muramyl dipeptide in guinea-pigs." Pflugers Arch, 1997;434(5):525-33. PMID: 9242715.
- [pubmed] Coulombe F, et al. "Muramyl dipeptide induces NOD2-dependent Ly6C(high) monocyte recruitment to the lungs and protects against influenza virus infection." PLoS One, 2012;7(5):e36734. PMID: 22590599.
- [pubmed] Piec PA, et al. "Muramyl Dipeptide Administration Delays Alzheimer's Disease Physiopathology via NOD2 Receptors." Cells, 2022;11(14). PMID: 35883683.
- [review] Salem M, et al. "Muramyl dipeptide responsive pathways in Crohn's disease: from NOD2 and beyond." Cell Mol Life Sci, 2013;70(18):3391-404. PMID: 23275943.
- [review] Jakopin Ž. "Murabutide revisited: a review of its pleiotropic biological effects." Curr Med Chem, 2013;20(16):2068-79. PMID: 23531213.
- [clinical-trial] Hiraoka A, et al. "Hematological response to the new synthetic muramyl dipeptide derivative muroctasin after chemotherapy in patients with malignant lymphoma. A randomized crossover trial." Arzneimittelforschung, 1988;38(10):1499-501. PMID: 3058133.
- [other] PubChem CID 451714, Muramyl Dipeptide: formula C19H32N4O11, molecular weight 492.5. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/451714
- [other] ChEMBL CHEMBL1779325, muramyl dipeptide (synonyms include N-acetylmuramyl dipeptide): maximum clinical phase 1 in the ChEMBL molecule record, read October 2, 2026 (the Registry's ChEMBL harvest). https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1779325/
Sources & Citations
Every study on this page was read from its PubMed record on October 28, 2026. The formula and weight come from PubChem, regulatory status from Drugs@FDA (openFDA) and the EMA medicines list, and trial status from ClinicalTrials.gov, read the same day. 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.