Neuromedin U
A gut and brain neuropeptide that suppresses appetite and simultaneously raises energy expenditure, now being engineered into long-acting analogues as a combination partner for incretins.
Also known as NMU, NmU-25, NMUR1/NMUR2 agonists
Animal data only — Rodent or other animal studies. Dose translation to humans is genuinely uncertain.
Robust rodent and primate preclinical data since the receptor deorphanisation in 2000. Long-acting analogues have entered early clinical development at several companies, but no phase 2 efficacy readout in humans had been published as of mid-2026.
How it works
Neuromedin U signals through two GPCRs with a clean division of labour: NMUR1 is peripheral, on gut, immune cells and adipose tissue, while NMUR2 dominates in the brain, particularly the paraventricular nucleus and arcuate nucleus. Central NMUR2 activation reduces feeding and increases energy expenditure and locomotor activity — the dual effect is what makes it attractive, because most anorectic peptides do nothing for expenditure. NMU knockout mice become obese and hyperphagic. NMUR1 activation in the periphery drives smooth muscle contraction and type 2 immune responses in the airway, which is the main liability: unmodified NMU causes gut cramping and has a role in allergic inflammation. Drug programmes have therefore focused on NMUR2-selective, lipidated or PEGylated long-acting analogues, several of which have shown additive weight loss with GLP-1 agonists in rodents and non-human primates.
Targets: NMUR1, NMUR2, Paraventricular nucleus feeding circuits
Dosing
| Protocol | Dose | Frequency | Route |
|---|---|---|---|
| No human protocol existsNot applicable. | — | not established | subcutaneous |
- · All published dosing is preclinical and body-weight-scaled. Native NMU has a half-life measured in minutes, so injecting the unmodified peptide subcutaneously accomplishes essentially nothing systemically.
Cycling
Not applicable.
Pharmacology
- Half-life
- Native NMU is cleared within minutes. Engineered analogues in development are designed for once-weekly dosing.
- Onset
- Acute suppression of feeding within an hour in animal models.
- Routes
- subcutaneous
- Molecule
- Endogenous neuropeptide, human 25-amino-acid amidated form
- Sequence length
- 25 amino acids
Handling
- Diluent
- Bacteriostatic water
- Lyophilised
- Freezer at -20 C.
- Reconstituted
- Refrigerated, days only.
Mixing
Research reagent only; C-terminal amidation is essential for receptor binding.
Side effects
- commonGastrointestinal cramping and smooth muscle contraction— A direct NMUR1 effect; the reason selective NMUR2 analogues are being pursued.
- commonUnknown human profile— No completed human trial has been published.
- uncommonBlood pressure elevation— NMU is sympathoexcitatory in animal models.
Do not use if
- Human use outside research.
- Asthma or atopic disease - NMUR1 signalling amplifies type 2 innate lymphoid cell responses in the airway.
Combining it
- synergysemaglutide — Additive weight loss shown preclinically; this combination is the explicit commercial thesis for the class.
What to monitor
- · Not applicable outside research.
Legal status
Research reagent. No approved product.
References
- Howard et al. 2000, Nature — identification of the NMU receptor and its role in regulating feeding (preclinical)
- Minamino et al. 1985 — original isolation of neuromedin U from porcine spinal cord (preclinical)
Mechanism in depth
A highly conserved peptide acting at NMUR1 in the periphery and NMUR2 in the brain. Central NMUR2 signalling suppresses food intake and increases energy expenditure; peripheral NMUR1 signalling affects smooth muscle and immune function, including a role in type 2 immunity. Receptor-selective analogues are the route being pursued precisely because the two receptors do different jobs.
What usually goes wrong
Non-selective neuromedin U causes marked blood pressure and smooth-muscle effects through NMUR1, which is why an unselective compound is not a viable weight-loss agent. Anything sold as generic 'neuromedin U' carries the peripheral effects along with the central ones.
Receptor targets
- NMUR1 (peripheral)
Smooth muscle contraction, immune modulation
- NMUR2 (central)
Reduced food intake, increased energy expenditure
Genuinely uncertain
- No human trial data.
- Whether NMUR2 selectivity can be achieved with adequate central exposure is unresolved.