Source comparison
Structural and Receptor Pharmacology Comparison
Both MT-II and PT-141 are cyclic lactam analogues of the core bioactive sequence of α-MSH (ACTH/MSH-family peptides; the most potent endogenous melanocortin). The cyclic lactam bridge between the D-Phe7 and Lys11 residues (cyclisation between an ε-amino group
This comparison does not assign a generated winner or score.
- Both MT-II and PT-141 are cyclic lactam analogues of the core bioactive sequence of α-MSH (ACTH/MSH-family peptides; the most potent endogenous melanocortin). The cyclic lactam bridge between the D-Phe7 and Lys11 residues (cyclisation between an ε-amino group and an α-carboxyl) constrains the peptide backbone into a β-turn conformation that optimises melanocortin receptor binding relative to the linear parent sequence.
- MT-II (cyclo[Nle4,Asp5,D-Phe7,Lys10]-α-MSH(4-10); molecular formula C₅₀H₆₉N₁₅O₉; ~1024.2 Da) is a 7-residue cyclic peptide binding all five human melanocortin receptors (MC1R through MC5R) with high affinity, with relative potency approximately: MC1R ~0.3 nM > MC3R ~0.9 nM > MC4R ~1.1 nM > MC5R ~3.8 nM, with MC2R (ACTH-specific receptor) showing minimal binding (Ki >1000 nM) — reflecting the requirement for the full ACTH 1–24 sequence for MC2R activation. MT-II is therefore an essentially pan-MC1/3/4/5R agonist with approximately equal potency at MC3R and MC4R.
- PT-141 (bremelanotide; cyclo[Nle4,Asp5,D-Phe7,Arg10]-α-MSH(4-10); molecular formula C₅₀H₆₈N₁₄O₁₀; ~1025.2 Da) differs from MT-II by a single conservative substitution: Lys10 → Arg10 in the ring closure. This single amino acid change alters the ring conformation modestly (Arg has a more extended, guanidinium-bearing side chain versus Lys’s ε-amino) and produces a receptor selectivity shift: PT-141 shows approximately 10-fold lower affinity at MC1R (~3.5 nM versus MT-II’s ~0.3 nM) while maintaining similar affinity at MC3R (~1.2 nM) and MC4R (~1.8 nM). PT-141 therefore has a more MC3R/MC4R-selective profile relative to MC1R compared to MT-II.
- This receptor selectivity difference has direct mechanistic implications: MT-II’s 10-fold higher MC1R affinity makes it the superior tool for melanocyte biology and anti-inflammatory MC1R research (MC1R is the dominant melanocortin receptor on melanocytes, monocytes, dendritic cells, and NK cells). PT-141’s relative MC1R sparing makes it more selectively biased toward the CNS and reproductive MC3R/MC4R biology, reducing the pigmentation and immune confounds that MT-II’s potent MC1R activation introduces in research designs focused on reproductive or CNS outcomes.