Research Chemical Designation & Liability
Compounds indexed in the MinMaxMuscle archive are strictly for laboratory research and development. They are NOT approved for human consumption. Theoretical dosing data is aggregated from clinical literature and must not be construed as medical instruction. Professional medical consultation is mandatory prior to any research application.
Alpha-MSH
Hormonal & Reproductive
Molecular Dossier
- Rank Index: 78
- Status: Research Only
- What does this mean?
- Molecular Structure: MW: 1664.9 Da | 13 AA | CAS: 581-05-5 | Sequence: Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂
About Alpha-MSH
Alpha-melanocyte-stimulating hormone (α-MSH) is a 13-amino acid endogenous peptide derived from proopiomelanocortin (POMC), the same precursor protein that gives rise to ACTH, beta-endorphin, and the melanotrophic peptides. It acts as an agonist at melanocortin receptors 1–4 (MC1R–MC4R), producing effects that vary dramatically by receptor subtype. At MC1R: stimulates melanin production in skin melanocytes — directly relevant to Melanotan I and II which are α-MSH analogues. At MC3R/MC4R: potent appetite suppression via hypothalamic nuclei, making α-MSH one of the body's primary anti-obesity signals; loss-of-function mutations in MC4R are the most common genetic cause of severe early-onset obesity. At MC1R and beyond: potent anti-inflammatory and immunomodulatory activity via NF-κB pathway suppression and pro-inflammatory cytokine inhibition, with research interest in inflammatory conditions, ischemia-reperfusion injury, and sepsis. Melanotan II (MT-II) and PT-141 (bremelanotide) are cyclic analogues developed from α-MSH with modified MC receptor selectivity. Clinically, α-MSH itself is not used therapeutically due to short half-life (<10 min), but its analogues and synthetic fragments (including Melanotan I, II and KPV — the C-terminal tripeptide α-MSH(11-13)) are subjects of active research. The superpotent analogue SHU9119 is used as a pharmacological MC3/4R antagonist tool compound. Understanding α-MSH is foundational to interpreting all melanocortin peptide research.
Clinical Focus
Melanocortin Receptor Agonism, Anti-Inflammation, Appetite Suppression
Archival Aliases
α-Melanocyte-Stimulating Hormone, POMC fragment, Melanocyte-stimulating hormone alpha
Frequently Asked Questions
What is the functional difference between MC1R and MC4R activation by α-MSH?
MC1R and MC4R are the two best-characterized melanocortin receptor subtypes with distinct tissue distribution and effects. MC1R is expressed primarily on melanocytes and immune cells; its activation by α-MSH drives melanin synthesis (tanning) and exerts potent anti-inflammatory effects on macrophages and dendritic cells. MC4R is expressed predominantly in hypothalamic neurons; its activation strongly suppresses appetite, increases energy expenditure, and regulates sexual function — loss-of-function MC4R mutations cause severe early-onset obesity. Melanotan I targets MC1R with high selectivity (primarily a tanning peptide), while Melanotan II and PT-141 are less selective and activate MC3R/MC4R as well, explaining their effects on libido and sexual function.
What is the relationship between α-MSH and the Melanotan peptides?
Melanotan I and Melanotan II are synthetic analogues of α-MSH developed at the University of Arizona in the 1980s–90s to create more potent, longer-lasting melanocortin agonists. α-MSH is the linear 13-amino acid template; Melanotan II introduces a cyclic structure (disulfide bridge) and D-amino acid substitutions that dramatically extend half-life (from <10 min to 1–2 hours), increase potency, and alter receptor selectivity. PT-141 (bremelanotide) is derived from Melanotan II with the N-terminal lactam ring removed, improving the safety profile while preserving MC4R-mediated sexual arousal activity. Understanding α-MSH is essential because all downstream melanocortin peptides are pharmacological attempts to improve upon its native structure.
How does α-MSH produce its anti-inflammatory effects?
α-MSH exerts anti-inflammatory effects through multiple complementary mechanisms: (1) It binds MC1R on macrophages, dendritic cells, and microglia, suppressing NF-κB nuclear translocation and reducing transcription of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). (2) It upregulates IL-10, an anti-inflammatory cytokine. (3) It can cross the blood-brain barrier to act on central immune cells (microglia), explaining its potential in neuroinflammatory conditions. (4) In peripheral tissues, it modulates neutrophil trafficking and T-cell activation. These effects are being studied for applications in ischemia-reperfusion injury, sepsis, inflammatory bowel disease, and traumatic brain injury.
Why is α-MSH's half-life so short and what does this mean for research use?
Native α-MSH has a circulating half-life of under 10 minutes in plasma, due to rapid cleavage by peptidases — particularly at the Met residue in position 4, which is an enzymatic vulnerability. This short half-life means exogenous α-MSH requires either continuous infusion or would need to be reformulated as a stable analogue for any practical therapeutic application. The research community therefore works primarily with its synthetic analogues (Melanotan I, II, KPV, SHU9119) rather than native α-MSH itself. KPV (the C-terminal tripeptide α-MSH 11-13) is particularly interesting as a topically or intrarectally delivered anti-inflammatory fragment with its own receptor activity and improved stability.
Clinical Data Matrix
| Parameter | Clinical Value |
|---|---|
| Molecular Weight | MW: 1664.9 Da | 13 AA | CAS: 581-05-5 | Sequence: Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂ |
| Primary Pathway | Hormonal & Reproductive |
| Research Phase | Research Only |
Clinical Pros
- Highly selective receptor modulation
- Documented efficacy in Phase II trials
- Minimal systemic cross-reactivity
Research Limitations
- Limited long-term human data
- Strict storage and reconstitution requirements
- Potential for acute homeostatic feedback loops
Community Discussion
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Data Verified: 2026-05-15