Chemical Identity

Mechanism of Action

Melanotan I (MT-I) is a full-length linear synthetic analogue of α-MSH differing by two key substitutions: norleucine (Nle) at position 4 and D-phenylalanine (D-Phe) at position 7. These modifications enhance MC1R binding affinity and resistance to enzymatic degradation, while the linear full-length structure provides greater MC1R selectivity compared to the shorter cyclic MT-II analogue.

MC1R is a Gαs-coupled GPCR expressed on epidermal melanocytes, keratinocytes, and immune cells. Upon binding by MT-I, MC1R activates adenylyl cyclase, elevating cAMP and driving PKA-mediated CREB phosphorylation, upregulating MITF — the master transcription factor for tyrosinase, TYRP1, and TYRP2.

Beyond melanogenesis, MC1R activation enhances nucleotide excision repair (NER) capacity in melanocytes. MT-I’s relative MC1R selectivity makes it a preferred tool compound for isolating MC1R-specific effects from broader melanocortin pharmacology.

Research Applications

• MC1R-selective pharmacology and binding affinity studies
• Eumelanin biosynthesis pathway research (MITF/tyrosinase axis)
• Nucleotide excision repair (NER) and DNA damage response studies
• cAMP/PKA/CREB signaling in MC1R-expressing cell lines
• Comparative α-MSH analogue selectivity research (MT-I vs. MT-II vs. α-MSH)
• UV-response biology and photoprotection mechanism research

Peer-Reviewed References

1. Kadekaro AL, et al. Alpha-melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes. Cancer Res. 2005;65(10):4292–4299.
2. Scott MC, et al. Human melanocortin 1 receptor variants and melanocyte response to UV radiation. J Cell Sci. 2002;115(Pt 11):2349–2357.
3. Lim HW, et al. Afamelanotide and narrowband UV-B phototherapy for vitiligo. JAMA Dermatol. 2019;155(10):1234–1236.

Testing & Supply Specifications

Every Blueprint Labs batch is independently verified by third-party analytical laboratories prior to release. Identity and purity confirmed via HPLC and mass spectrometry. Full batch records maintained for chain-of-custody traceability.

No COA available for this batch.