PT-141 (Bremelanotide)

PT-141 / bremelanotide (CAS 189691-06-3) has the sequence Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH. The N-terminus is acetylated, the C-terminus is a free acid, and a lactam bridge between the side-chain carboxyl of Asp and the side-chain amine of Lys closes the central six residues into a constrained ring.

Molecular formula C50H68N14O10, theoretical monoisotopic mass 1024.5243 Da, average mass approximately 1025.18 Da. The molecule is the active pharmaceutical ingredient in an FDA-approved product for a specific clinical indication; CertikLabs verifies the chemistry of supplied material and does not publish clinical guidance.

PT-141 is produced by Fmoc solid-phase peptide synthesis with orthogonal side-chain protection on Asp and Lys, followed by an on-resin or solution-phase cyclization step that forms the lactam bridge. The dominant failure modes:

• Incomplete cyclization. Linear PT-141 (no lactam bridge) is the highest-impact impurity — same composition by AAA, distinct by HRMS (no -H2O), and pharmacologically inactive.
• D-Phe racemization. The central D-phenylalanine can racemize to the L-form under repeated base deprotection; the resulting diastereomer is nearly co-eluting on standard achiral HPLC.
• Tryptophan oxidation. The Trp side chain is light- and oxidation-sensitive; storage degradants (kynurenine, hydroxytryptophan) show up as small mass shifts (+4, +16, +32 Da) that an extracted-ion screen catches.

Additional analytes: cyclization isomers (head-to-tail vs side-chain lactam), deamidation, and residual counter-ion. See common peptide impurities for the full taxonomy.

The standard CertikLabs panel for a PT-141 batch:

• RP-HPLC purity (C18, 0.1% TFA / MeCN, UV 214 and 280 nm)
• LC-HRMS identity (ESI-Q-TOF, theoretical [M+H]+ 1025.5316)
• MS/MS fragmentation to confirm the Asp-Lys lactam ring topology
• Chiral HPLC or Marfey's analysis to confirm D-Phe stereochemistry
• Trp-oxidation screen by extracted-ion chromatograms (Δ+16, +32 Da)

MS/MS fragmentation is the linchpin: the lactam-bridged ring produces a characteristic fragmentation pattern that the open-chain (linear) impurity does not, so identity verification confirms not just the mass but the topology.

Non-selective agonist of the melanocortin receptors, with activity at MC1R, MC3R, MC4R, and MC5R. Published pharmacology centers on MC4R activation in the central nervous system. CertikLabs does not publish dosing or clinical recommendations.

Primary sources:

• Molinoff P.B. et al., PT-141: a melanocortin agonist for the treatment of sexual dysfunction.(PMID 14684464)
• Diamond L.E. et al., Co-administration of bremelanotide with sildenafil in patients with erectile dysfunction.(PMID 16422852)

CertikLabs does not publish dosing, administration routes, or clinical recommendations for PT-141.

Lyophilized PT-141 is generally stable refrigerated and protected from light. In aqueous solution the tryptophan residue is light- and oxidation-sensitive and the lactam bridge can be slowly hydrolyzed at elevated pH; analytical re-verification of any working solution is required.