Selective MC1R AgonistFDA-Approved Analog (Scenesse)EPP TreatmentTanning Peptideα-MSH Linear Analog
Melanotan I (MT-I, afamelanotide) is a linear α-melanocyte stimulating hormone (α-MSH) analog that selectively activates the MC1R receptor — producing melanogenesis (skin darkening) with minimal activation of MC3R, MC4R, or MC5R. This selectivity is its key research advantage over Melanotan II: MT-I drives tanning without the appetite suppression, libido effects, spontaneous erections, and nausea associated with MT-II’s MC4R activation. Afamelanotide (Scenesse, Clinuvel) is the FDA and EMA-approved pharmaceutical form of MT-I, specifically indicated for erythropoietic protoporphyria (EPP) — a rare photodermatosis where MT-I’s melanogenesis protects against phototoxic pain from sun exposure. MT-I is therefore the only melanocortin agonist with pharmaceutical-grade regulatory data.
MC1R selective
Tanning without MC4R side effects
1646.9 g/mol
MW — linear α-MSH analog
FDA-approved
Scenesse for erythropoietic protoporphyria
~40 min
Plasma half-life
≥99%
Purity — HPLC verified
Melanotan I (Afamelanotide) — Specifications
Melanotan I (Afamelanotide) — specifications
Property
Value
CAS Number
75921-69-6
Molecular Formula
C₇₈H₁₁₁N₂₁O₁₉
Molecular Weight
1646.9 g/mol
Half-life
~40 min plasma; tanning effect days (depot from SC)
Class
Selective MC1R agonist (α-MSH analog)
Purity
≥99% HPLC verified
COA
Janoshik independent third-party
⚙️
Mechanism of Action — Melanotan I (Afamelanotide)
MT-I (afamelanotide) activates melanocortin receptor 1 (MC1R) — a Gs-coupled GPCR expressed on melanocytes, keratinocytes, fibroblasts, and immune cells:
MITF targets: TYR (tyrosinase), TYRP1, DCT — rate-limiting enzymes in melanin synthesis. Both eumelanin (brown/black) and phaeomelanin (red/yellow) pathways are upregulated but eumelanin increases preferentially
Eumelanin UV protection: Eumelanin absorbs UV radiation more effectively than phaeomelanin — provides photoprotection. Basis for EPP use.
MC1R vs MC4R selectivity: MT-I has ~100× selectivity for MC1R over MC4R. MT-II has similar affinity for MC1R and MC4R — explaining the different side effect profiles.
Why MC1R selectivity matters — MT-I vs MT-II for melanogenesis research
MT-II activates MC4R (appetite, libido, erections, nausea) in addition to MC1R (tanning). For research studying pure MC1R-mediated melanogenesis, MT-II’s MC4R activation is a confounder — body weight and food intake changes from MC4R activity complicate dose-response interpretation. MT-I allows isolated MC1R biology. For researchers studying the full melanocortin axis including MC4R, MT-II is the tool. For isolated melanogenesis mechanism studies, MT-I is mechanistically essential.
MT-I 0.1–1 mg/kg SC daily × 14 days vs MT-II vs vehicle. Skin melanin content (Fontana-Masson), eumelanin/phaeomelanin ratio (HPLC acid hydrolysis), TYR/TYRP1/DCT mRNA (qPCR), MITF protein (WB), MC4R-mediated readouts (food intake, body weight, plasma LH) — confirms MC1R selectivity profile.
Protocol 2: Photoprotection model
MT-I 0.5 mg/kg SC daily × 10 days in Skh-1 hairless mice. UV irradiation (1–3 MED broadband UVB). Erythema score, sunburn cell count (H&E), CPD formation (IHC), thymine dimer content (ELISA), skin melanin index (reflectance spectrophotometry).
Protocol 3: MC1R vs MC4R dissection
MT-I vs MT-II equimolar SC in C57BL/6 mice. Melanin (skin biopsy), food intake, body weight, penile erection frequency (scoring), plasma corticosterone (MC2R proxy), serum LH (HPG axis via MC3/4R) — complete receptor selectivity fingerprint.
Protocol 4: In vitro melanocyte melanogenesis
MT-I 1 nM–1 µM in primary human melanocytes. cAMP (competitive binding, 30 min), MITF/TYR protein (WB, 24hr), melanin content (spectrophotometric, 72hr), eumelanin/phaeomelanin HPLC (96hr). Dose-response and time course.
❓
Frequently Asked Questions
What is Melanotan I?
Melanotan I (MT-I, afamelanotide) is a selective MC1R agonist that drives melanogenesis (skin darkening) with minimal MC4R activation. It is FDA and EMA-approved as Scenesse for erythropoietic protoporphyria — the only approved melanocortin agonist.
What is the difference between Melanotan I and Melanotan II?
MT-I is selective for MC1R — it produces tanning with minimal MC4R-mediated effects (appetite suppression, libido, nausea, erections). MT-II activates MC1R through MC5R broadly — stronger tanning but with significant MC4R side effects. For isolated MC1R melanogenesis research, MT-I is the mechanistically cleaner tool.
What is Scenesse?
Scenesse (afamelanotide) is the FDA/EMA-approved pharmaceutical form of MT-I, specifically for erythropoietic protoporphyria (EPP). It is administered as a biodegradable SC implant releasing afamelanotide over 60 days. QSC MT-I is research-grade material with the same peptide sequence — not the same product.
Does Melanotan I cause side effects like Melanotan II?
MT-I has a much cleaner side effect profile because of MC1R selectivity. The nausea, spontaneous erections, and appetite suppression associated with MT-II are primarily MC4R-mediated — and MT-I has ~100× lower MC4R affinity. Flushing (likely MC1R-mediated) can occur with MT-I.
What formats does QSC supply Melanotan I in?
QSC supplies Melanotan I as 10mg lyophilised vials in 10-vial and 20-vial kits (100mg and 200mg total), ≥99% purity HPLC verified with Janoshik COA. Ships from domestic QSC warehouses in USA, EU, UK, Canada, and Australia.
Research Use Only: All QSC compounds are sold strictly for laboratory research purposes. Not for human use. Not approved by the FDA or equivalent regulatory bodies for human administration. All purchases confirm research intent and compliance with applicable local regulations.
