Melanotan I (MT-1) — Peptide Protocol Wiki reference

Is Melanotan-1 FDA approved?

Melanotan-1 is currently in the approved stage.

FDA-approved (October 2019) as SCENESSE for adults with EPP Regulations vary by country and may change.

Melanotan-1 (Afamelanotide): Skin Peptide Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides?

Reproductive Health Skin & Hair PT-141 PT-141 (Bremelanotide): FDA-approved for hypoactive sexual desire.

Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About Melanotan-1 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides Melanotan-1 Skin & Hair Cosmetic & Anti-Wrinkle approved Melanotan-1 Also known as: MT-1, MT1, Melanotan I, MT-I, Afamelanotide, Scenesse, NDP-alpha-MSH, CUV1647 Compare with 2 peptide s Research compiled by Peptide Protocol Wiki 📅 Updated February 1, 2026 Citations Verified TL;DR Melanotan-1 (Afamelanotide) is a synthetic 13-amino acid linear analog of alpha-melanocyte-stimulating hormone (alpha-MSH).

It is EMA-approved (as Scenesse) for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP) and has been investigated for broader photoprotective applications.

Browse all skin peptides → Table of Contents 📌 TL;DR • EMA-approved for erythropoietic protoporphyria (EPP) as Scenesse • Stimulates melanogenesis for enhanced photoprotection • More selective MC1R agonist compared to Melanotan-2 • Demonstrated UV protection in clinical trials Community-Reported Side Effects Anecdotal ?

Quick-Reference Photoprotection and skin tanning via MC1R agonism (approved as afamelanotide for EPP) 💉 Dosing Amount 0.16 mg/kg daily (injection protocol); 16 mg implant every 2 months (approved) Frequency Daily for 10 days per cycle (injection); every 2 months (implant) Duration 10-day injection cycles repeated monthly for 3 months; or 3-4 implants per year seasonally 💊 Administration Route SC Schedule Daily for 10 days per cycle (injection); every 2 months (implant) Timing No specific timing; implant insertion by specialist physician 📅 Cycle Duration 10-day injection cycles repeated monthly for 3 months; or 3-4 implants per year seasonally Repeatable Yes Course-based protocol with rest periods Preparation & Storage Diluent: Sterile water ⚗️ Suggested Bloodwork ( 3 tests) CMP with liver enzymes When: Baseline Why: Baseline metabolic function CBC When: Baseline Why: Baseline blood counts Liver enzymes When: 3 months Why: Monitor hepatic function 💡 Key Considerations → SC injection bioavailability is approximately 100% relative to IV → Half-life is approximately 1.3 hours after SC injection → Contraindication: Avoid in melanoma or history of melanoma; use with caution in patients with many atypical nevi Subscribe to unlock this content Get weekly peptide research summaries, new study alerts, and protocol updates — free.

uce UV‑induced cyclobutane pyrimidine/thymine dimers, and bolster antioxidant defenses, thereby decreasing genotoxic burden after UV exposure.

Restore access No thanks, continue reading Related Reading Peptide Melanotan-2 melanocortin receptor agonist Peptide PT-141 bremelanotide melanocortin agonist Comparison Melanotan-1 vs Melanotan-2: Tanning Peptides Compared How Melanotan-1 works at the cellular level Overview of Melanotan-1 benefits and applications Scientific Details Molecular Formula C78H111N21O19 Molecular Weight 1646.85 Da CAS Number 75921-69-6 Sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 What is Melanotan-1?

Mechanism of Action # Melanotan‑1 (afamelanotide; NDP‑α‑MSH) is a synthetic α‑MSH analog that agonizes melanocortin receptors, with its principal pharmacodynamic effects mediated through MC1R on melanocytes and immune cells.

It is generally characterized as a nonselective melanocortin agonist (inactive at MC2R), but exhibits high affinity and strong cAMP efficacy at MC1R relative to native α‑MSH, consistent with its clinical pigmentation and photoprotective effects.

titutions in afamelanotide increase MC1R affinity and cAMP potency (added ligand–receptor interactions), while the receptor’s intracellular and extracellular loops contribute to Gs engagement and ligand selectivity.

Canonical cAMP pathway and melanogenesis.

Elevated cAMP activates PKA, which phosphorylates/activates CREB, driving expression of MITF and MITF‑dependent melanogenic genes, including tyrosinase (TYR), TYRP1, and DCT/TYRP2.

These changes increase tyrosinase activity, promote eumelanin biosynthesis in melanosomes, and enhance melanosome maturation and transfer to keratinocytes, yielding photoprotective pigmentation.

Relative to α‑MSH, Melanotan‑1 produces stronger cAMP signaling and eumelanin accumulation in human melanocytes.

Adjacent signaling nodes (ERK/MAPK and PI3K/AKT).

In melanocytes, MC1R activation engages additional pathways that modulate MITF and cell survival.

cAMP‑independent signals via cKIT can activate NRAS–BRAF–MEK–ERK, leading to MITF phosphorylation and regulation of proliferation/differentiation; PI3K–AKT activation has also been observed, supporting survival and antioxidant defenses.

MC1R signaling induced by Melanotan‑1 enhances genome maintenance programs in melanocytes.

Increased cAMP/PKA activity and associated signaling accelerate nucleotide excision repair (NER), red

In clinical contexts, afamelanotide‑induced pigmentation was accompanied by reduced thymine dimer formation, consistent with enhanced DNA repair and photoprotection.

MC1R is expressed on monocytes/macrophages and other immune cells.

Melanotan‑1/α‑MSH‑like agonism increases cAMP and PKA signaling, which inhibits NF‑κB activation (via preservation of IκB), activates CREB, induces anti‑inflammatory mediators (e.g., IL‑10), and suppresses pro‑inflammatory cytokines (TNF‑α, IL‑1, IL‑6, IL‑8, IL‑12), adhesion molecules, and iNOS.

MC1R activation can also promote macrophage cholesterol efflux via ABCA1/ABCG1 and confer neuroprotective effects through cAMP/PKA/Nurr1 signaling, illustrating broader anti‑inflammatory and tissue‑protective roles beyond pigmentation.

Keratinocyte–melanocyte paracrine context and receptor regulation.

In the epidermis, UV exposure induces keratinocyte production of α‑MSH/ACTH, which activate MC1R on melanocytes; Melanotan‑1 pharmacologically mimics/enhances this paracrine signal to increase eumelanin and UV resistance.

Endogenous antagonists and competitive ligands, including agouti signaling protein (ASIP) and β‑defensin 3, modulate MC1R tone by lowering cAMP output, thereby counterbalancing melanocortin stimulation.

Receptor selectivity across the melanocortin famil

This nonselectivity underlies the potential for extra‑cutaneous actions (e.g., overlapping with other melanocortin pathways), though MC1R’s high affinity and strong signaling efficacy make it the principal molecular target in skin and immune contexts.

Covers MC4R mechanism, Vyleesi trial data, dosing, and side effects.

The immediate molecular outputs of Melanotan‑1–MC1R signaling include: increased intracellular cAMP; PKA activation; CREB phosphorylation; MITF induction; transcriptional upregulation of melanogenesis genes (TYR, TYRP1, DCT); enhanced NER gene activity and DNA repair capacity; suppression of NF‑κB target genes; and induction of anti‑inflammatory mediators.

Together, these signaling modules explain its pigmentation, photoprotective, and anti‑inflammatory profiles.

Erythropoietic protoporphyria (EPP): randomized phase 3 trials • European Union trial (9 months, five implants): In EPP patients, afamelanotide increased pain‑free direct sunlight exposure (10:00–15:00) with median 6.0 h per patient versus 0.8 h on placebo; mean 20.4±40.5 vs 5.6±9.3 h.

Embedded summary table: Component Key details for Melanotan-1 Main downstream effects / targets Notes Primary receptor(s) & selectivity Binds MC1R with high affinity/potency; described as a non‑selective MCR agonist (except MC2R) — activates other MCRs to varying degrees MC1R activation drives pigmentation and extra‑pigmentary MC1R responses (also can engage other MCRs) Clinically used as afamelanotide (EPP); nonselectivity implies possible off‑target MCR effects G protein coupling Couples primarily to Gαs at MC1R → stimulates adenylyl cyclase → raises intracellular cAMP ↑ cAMP → activation of

PKA (proximal step) Canonical GPCR Gs mechanism for MC1R agonists Canonical cAMP pathway PKA → CREB activation → upregulation of MITF transcriptional network; increases melanogenic enzyme expression (TYR, TYRP1, DCT) Increased tyrosinase activity, eumelanin synthesis, melanosome maturation and transfer to keratinocytes Explains tanning/eumelanin increase and photoprotection MAPK / ERK pathway Can be engaged via cKIT→NRAS→BRAF→MEK→ERK (cAMP‑independent routes also reported); ERK phosphorylates/ modulates MITF MITF phosphorylation/state changes → affects melanocyte proliferation, differentiation and melanogenesis regulation ERK activation is context dependent; sustained hyperactivation may have oncogenic potential PI3K / AKT pathway PI3K→AKT signaling reported downstream of MC1R/cKIT signaling in melanocytes AKT activation promotes cell survival and antioxidant responses MC1R variants can alter PI3K signaling; implicated in survival/repair responses DNA repair & oxidative stress responses MC1R activation enhances nucleotide excision repair (NER), increases antioxidant defenses and reduces UV‑induced DNA lesions (e.g., thymine dimers) Lowered cyclobutane pyrimidine dimer formation, accelerated DNA repair, reduced genotoxicity Contributes to reduced UV damage and may modify melanoma risk Anti‑inflammatory signaling cAMP/PKA‑mediated inhibition of NF‑κB, induction of anti‑inflammatory mediators (e.g., IL‑10); reduces pro‑inflammatory cytokines; effects in monoc...

sed TNF‑α/IL‑1, reduced leukocyte infiltration and MAPK phosphorylation; neuroprotective/anti‑fibrotic effects reported Supports therapeutic anti‑inflammatory actions beyond pigmentation Keratinocyte–melanocyte paracrine context UV stimulates keratinocyte production of α‑MSH/ACTH → paracrine MC1R activation; afamelanotide mimics/enhances this signal Enhanced melanin production and transfer to keratinocytes → increased UV shielding Explains physiologic tanning response and clinical photoprotection Competitive modulators Agouti signaling protein (ASIP) acts as MC1R antagonist (reduces cAMP); β‑defensin 3 can compete with melanocortins Antagonism reduces melanogenesis and MC1R signaling output Important for regulation and pharmacological interpretation Structural / affinity notes Afamelanotide = Nle4, D‑Phe7 α‑MSH analogue; D‑Phe7 substitution increases receptor interactions (additional H‑bond with TM2); cryo‑EM structures v...

Structural basis for increased MC1R affinity and superior cAMP potency vs native α‑MSH Rationalizes enhanced potency/duration of action and informs selectivity/design Therapeutic Applications # Plan status: All objectives completed.