Cobalt PeptidesResearch Grade

Scientific Reference

PT-141 (Bremelanotide)

Evidence profile: Human Phase 3 evidence

PT-141 (bremelanotide) is a synthetic cyclic heptapeptide melanocortin receptor agonist, closely related in structure to melanotan II. The two share the same seven residues and the same lactam bridge between aspartic acid and lysine; they differ only at the C-terminus, which in PT-141 is a free carboxylic acid rather than an amide. Inside the ring sits His-D-Phe-Arg-Trp, the sequence through which melanocortin peptides engage their receptors. Its receptor pharmacology has been characterised in binding and cell-signalling assays and in animal studies, and it has also been the subject of human clinical research. Mechanistic work has concentrated on its action at MC4R in the brain.

Mechanism of Action

Bremelanotide has been reported to activate several melanocortin receptor subtypes, including MC1R, MC3R, MC4R and MC5R, so it is not selective for one. These receptors are G-protein-coupled and signal mainly through Gs and cyclic AMP. MC3R and MC4R are expressed in the hypothalamus and elsewhere in the central nervous system, where their endogenous agonists are α-MSH and related melanocortins and where agouti-related peptide acts as an antagonist and inverse agonist. It shares this lack of subtype selectivity with melanotan II, from which it differs by a single terminal group.

Molecular Information

  • Type: Melanocortin receptor agonist (cyclic heptapeptide)
  • Length: 7 amino acids
  • Molecular weight: 1025.2 g/mol
  • Molecular formula: C50H68N14O10
  • CAS: 189691-06-3

Published Research

  • RECONNECT (Studies 301 and 302)

    Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials

    Kingsberg SA et al. · Obstetrics and gynecology · 2019 · Clinical

    PMID 31599840 — View on PubMed

  • Safety Profile of Bremelanotide Across the Clinical Development Program

    Clayton AH et al. · Journal of women's health (2002) · 2022 · Clinical

    PMID 35147466 — View on PubMed

  • Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide

    Simon JA et al. · Journal of women's health (2002) · 2022 · Clinical

    PMID 35230162 — View on PubMed

  • The Patient Experience of Premenopausal Women Treated with Bremelanotide for Hypoactive Sexual Desire Disorder: RECONNECT Exit Study Results

    Koochaki P et al. · Journal of women's health (2002) · 2021 · Clinical

    PMID 33538638 — View on PubMed

  • Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants

    Clayton AH et al. · Clinical therapeutics · 2017 · Clinical

    PMID 28189361 — View on PubMed

  • Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide

    White WB et al. · Journal of hypertension · 2017 · Clinical

    PMID 27977473 — View on PubMed