Verified Active Pharmaceutical Ingredients synthesized under rigorous cGMP protocols for global clinical trials and commercial distribution.
Bremelanotide (PT-141, CAS 189691-06-3) represents a transformative synthetic cyclic heptapeptide analog of alpha-MSH (melanocyte-stimulating hormone), operating downstream via central melanocortin receptor agonism (MC3R and MC4R).
Unlike phosphodiesterase-5 (PDE5) inhibitors that act exclusively through peripheral vascular smooth muscle relaxation, PT-141 activates central nervous system neuromodulators within the hypothalamus, providing therapeutic utility across hypoactive sexual desire disorder (HSDD) and treatment-resistant neurovascular deficits.
The core technical barrier in PT-141 manufacturing is cyclization. Synthesizing the linear sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH requires selective side-chain lactam bridge closure without inducing Asp epimerization, racemization of D-Phe, or premature Trp degradation during acidolytic cleavage.
Modern compounding pharmacies, generic formulation developers, and biopharmaceutical sponsors require uninterrupted access to multi-kilogram batches accompanied by compliant DMF filings, low bioburden profiles, and validated residual solvent thresholds (ICH Q3C compliant).
Procurement pricing varies dramatically depending on peptide net content, counter-ion exchange (Acetate vs. TFA-free), sterile lyophilization packaging, and regulatory documentation completeness.
| Procurement Tier | Order Volume | Target Purity (RP-HPLC) | Counter-Ion Profile | Indicative Price Range | Documentation Scope |
|---|---|---|---|---|---|
| Preclinical Pilot | 10g – 50g | ≥ 98.0% | TFA / Residual Acetate | $45 – $75 / gram | Standard CoA, MS, RP-HPLC Chromatogram |
| Scale-Up Development | 100g – 500g | ≥ 99.0% | Acetate (≤ 10.0%) | $28 – $42 / gram | Full CoA, MS, HPLC, Karl Fischer, Amino Acid Analysis |
| Pilot Commercial (cGMP) | 1 kg – 5 kg | ≥ 99.5% (Single max ≤ 0.2%) | Pharma Grade Acetate | $14,000 – $22,000 / kg | Open Part DMF, Elemental Impurities (Q3D), Endotoxin |
| Commercial Multi-Kilogram | 10 kg – 50 kg+ | ≥ 99.5% (Enantiomeric Purity ≥ 99.8%) | Pure Controlled Acetate | Contract Price / CDMO Agreement | Full cGMP CTD Dossier Module 3, Site Audit Access, Stability |
Solid-Phase Peptide Synthesis (SPPS) scaling of Bremelanotide demands strict chemical orchestration to minimize related diastereomeric byproducts and optimize high-throughput crystallization.
Execution utilizes low-loaded 2-Chlorotrityl chloride (CTC) resin or Wang resin to mitigate steric crowding during the assembly of the protected intermediate Ac-Nle-Asp(OAll)-His(Trt)-D-Phe-Arg(Pbf)-Trp(Boc)-Lys(Alloc)-Resin. Orthogonal allyl-based protection ensures selective deprotection prior to on-resin macrocyclization.
Deprotection of Allyl/Alloc groups mediated by Pd(PPh3)4 in the presence of phenylsilane scavengers is followed by amide linkage closure between Asp and Lys. Leveraging PyBOP or HATU in DIPEA ensures cyclization rates exceeding 94%, suppressing linear oligomer formation and preventing D-Phe racemization down to < 0.15%.
Crude cleavage yields are purified using dual-stage axial-compression preparative RP-HPLC with C18 stationary phases. A dedicated second run executes dynamic ion-exchange, replacing trifluoroacetate adducts with pharmaceutical acetate. Subsequent terminal filtration through 0.22 μm PES filters precedes sterile lyophilization.
Navigating global chemical commerce requires rigorous vendor auditing. Qualified contract manufacturing organizations (CMOs) must satisfy strict analytical parameters before approval.
Insist on high-resolution UHPLC chromatograms coupled with Orbitrap MS/MS data. The critical impurity profile for PT-141 involves D-Phe stereoisomers, des-Arg truncations, and Trp-oxidation derivatives. Suppliers must demonstrate baseline separation with peak purity indices confirming absence of co-eluting degradants.
TFA (Trifluoroacetic acid) residues introduce cellular toxicity and regulatory non-compliance in finished parenteral formulations. Verified manufacturers must provide quantitation via Ion Chromatography (IC) verifying acetate content between 4.0% and 10.0%, with residual TFA strictly suppressed below 0.1% (w/w).
Lyophilized peptides intended for compounding or formulation into autoinjectors require stringent microbiological control. Cleanroom Grade C/A processing environments ensure bioburden levels < 10 CFU/g and bacterial endotoxins quantified via kinetic chromogenic LAL assays at < 0.1 EU/mg.
PT-141 in lyophilized solid form displays optimal stability when preserved at -20°C. Suppliers must provide real-time and accelerated stability data (25°C/60% RH) under ICH Q1A(R2) conditions, executed in validated temperature-monitored vacuum containers with humidity barrier integrity.
Navigating global peptide transactions across US FDA, EMA, NMPA, and GCC health ministries requires seamless dossier integration and transparent customs handling.
Comprehensive Type II Active Pharmaceutical Ingredient Drug Master Files (DMF) maintained in eCTD format. Ready assistance for ANDA reference filings, Section 503A/503B compounding quality compliance, and GDUFA facility fee verification.
ASMF (Active Substance Master File) dossiers aligned with EDQM chemical monograph guidelines. Integrated Qualified Person (QP) Declaration auditing capability and REACH chemical registration compliance for raw intermediate imports.
Dedicated regulatory desks supporting legalized Certificate of Pharmaceutical Product (CPP), localized GMP site certifications, and specialized customs clearance using dual dry-ice packaging to guarantee viability upon arrival.
Authoritative technical answers to common queries submitted by industrial synthesis directors and pharmaceutical procurement officers.
Procure custom synthesized APIs, GLP-1/GLP-2 receptor agonists, and immunomodulatory peptide standards manufactured for commercial formulation scale.
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