Degarelix Acetate | CAS 214766-78-6 / 934016-19-0 | GnRH Receptor Antagonist (Research Use Only) | Knowlux

Product Description

Degarelix Acetate, CAS 214766-78-6 (free peptide basis) / 934016-19-0 (acetate salt), is a synthetic linear decapeptide gonadotropin-releasing hormone (GnRH) receptor antagonist supplied by Knowlux for laboratory research use. The sequence is Ac-D-2-Nal-D-4-Cl-Phe-D-3-Pal-Ser-4-Aph(Hor)-4-D-Aph(Cbm)-Leu-Lys(ipr)-Pro-D-Ala-NH2. The free peptide molecular formula is C82H103ClN18O16 (MW 1632.26); the acetate salt corresponds to C84H107ClN18O18 (MW 1692.31). Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification: Degarelix is a case in which the CAS number most frequently used in commercial listings belongs to the free peptide, while the product actually supplied is almost always the acetate salt under a separate registry. CAS 214766-78-6 is the free peptide (net Degarelix) registry and is the identifier applied across ChemicalBook, Selleck, MedChemExpress, and the WHO ATC index. The acetate salt is separately registered under CAS 934016-19-0, with molecular formula C84H107ClN18O18 (equivalently C82H103ClN18O16.C2H4O2) and molecular weight 1692.31. Selleck and MedChemExpress both list CAS 214766-78-6 alongside the free peptide molecular weight 1632.26, while MedChemExpress, InvivoChem, Aobious, and Szabo Scandic list CAS 934016-19-0 alongside the acetate formula and MW 1692.31. A third registry, CAS 934246-14-7, appears on Pharmaffiliates for a Degarelix Acetate Hydrate grade. Knowlux specifies the salt stoichiometry, acetate content, and water content per lot on the COA. Buyers should confirm whether the quoted material is reported on a free-peptide or acetate-salt basis before procurement, as the 60 g/mol counter-ion mass is material for molarity calculations.

Structural Note: Degarelix is distinguished from earlier GnRH antagonists by the incorporation of 4-ureidophenylalanine (4-Aph(Cbm)) at position 6 and a 2,6-dioxohexahydropyrimidine-4-carboxamido-phenylalanine (4-Aph(Hor)) at position 5. This structural modification is the basis for two clinically relevant properties: prolonged receptor occupancy and a markedly reduced histamine-releasing capacity relative to Abarelix and Ganirelix. The peptide is linear and contains no cysteine or disulfide bonds. The C-terminus is D-alaninamide (D-Ala-NH2), and the N-terminus is acetylated.

Product Parameters

Product Details

1. Overview

Degarelix is a third-generation synthetic decapeptide GnRH receptor antagonist developed for the treatment of advanced hormone-dependent prostate cancer. It binds the pituitary GnRH receptor competitively and reversibly, producing immediate and sustained suppression of luteinizing hormone (LH) release and, consequently, of testosterone. Unlike GnRH agonists, Degarelix does not produce an initial testosterone surge or flare, a pharmacological distinction that has clinical relevance in patients with metastatic disease. In clinical medicine, Degarelix Acetate is marketed as Firmagon and received FDA approval in 2008. The material supplied under this specification is research-grade and is not intended for human administration. Knowlux supplies this compound strictly for laboratory investigation of GnRH receptor pharmacology, androgen deprivation biology, and the structure-activity relationships that distinguish third-generation antagonists from the earlier Abarelix and Ganirelix scaffolds.

2. Receptor Pharmacology and the Histamine-Release Advantage

Degarelix binds the human GnRH receptor with high affinity and produces competitive antagonism of GnRH-stimulated signaling. MedChemExpress and Selleck report an IC50 of 3 nM in HEK293 cells expressing the human GnRH receptor, a value widely cited as the primary potency reference for this compound. Guide to Pharmacology and ChEMBL curated data provide a broader set of orthogonal constants from independent assays: pKd 9.2 (Kd 0.63 nM) for competitive antagonism in a reporter gene assay; pKi 8.77 (Ki 1.7 nM); pIC50 8.06 (IC50 8.8 nM) in HEK293 cells; pIC50 8.79 (IC50 1.64 nM) in a second HEK293 reporter assay; and pIC50 9.24 (IC50 0.58 nM) for inhibition of GnRH-induced LH secretion. These values span approximately 0.6 nM to 8.8 nM depending on assay format, receptor density, and readout, with the 3 nM figure representing a central consensus for the recombinant human receptor.

The most consequential pharmacological difference between Degarelix and the earlier GnRH antagonists is its histamine-releasing profile. MedChemExpress reports that Degarelix shows only very weak histamine-releasing properties and has the lowest capacity for histamine release among the LHRH antagonists tested, including Cetrorelix, Abarelix, and Ganirelix. This property is structurally attributable to the 4-Aph(Hor) and 4-D-Aph(Cbm) substitutions and is the pharmacological rationale for the reduced hypersensitivity liability that distinguishes Degarelix from Abarelix, which was withdrawn from the US market in 2006 due to immediate-onset histamine-mediated reactions. For research designs in which mast cell activation or pseudoallergic mechanisms could confound interpretation, Degarelix serves as a low-histamine-release comparator within the GnRH antagonist series. These values are assay- and system-dependent and are provided for scientific reference only.

3. Research Applications

Published pharmacological characterizations and documented protocols describe the following research applications:

• GnRH receptor binding and functional antagonist assays (LH suppression, reporter gene antagonism)

• Androgen deprivation and prostate cancer research models (prostate cell line viability and apoptosis studies)

• Comparative histamine-release profiling across GnRH antagonists (Degarelix as the low-release comparator)

• Structure-activity relationship studies of position-5 and position-6 substitutions in the antagonist series

• Atherosclerosis and metabolic research models (Degarelix used to suppress testosterone/FSH in ApoE-deficient mice)

• Reference standard development for HPLC and LC-MS analytical methods

These descriptions are derived from published research and are provided for scientific reference only. They do not constitute clinical guidance or dosing recommendations.

Quality Control

Solubility and Handling

Solubility: Degarelix Acetate solubility is batch-, salt-form-, and source-dependent, and the reported values span a range that requires empirical confirmation on the specific lot. ChemicalBook lists DMSO 10 mg/mL (6.13 mM) and water 25 mg/mL (15.32 mM) for the CAS 214766-78-6 material. Selleck's batch-tested experimental data for its acetate salt reports DMSO 33 mg/mL and water 33 mg/mL, with ethanol insoluble, and notes that moisture-contaminated DMSO reduces solubility and freshly opened anhydrous DMSO should be used. MedChemExpress reports DMSO 10 mg/mL (5.91 mM) with ultrasonic and warming to 60C for its acetate salt. Szabo Scandic reports approximately 30 mg/mL in DMSO and DMF, approximately 0.25 mg/mL in ethanol, and approximately 10 mg/mL in PBS (pH 7.2) for the acetate salt. For in vivo formulation, MedChemExpress describes a vehicle of 10% DMSO -> 40% PEG300 -> 5% Tween-80 -> 45% saline achieving >=1 mg/mL (0.59 mM) as a clear solution. For practical stock preparation, DMSO at 10 mg/mL is the most consistently supported value across the principal suppliers; water solubility may be higher on specific lots, but Selleck's 33 mg/mL figure should not be assumed to apply universally. Aqueous solutions should be used fresh; Szabo Scandic explicitly does not recommend storing aqueous solutions for more than one day.

Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. ChemicalBook assigns GHS08 (Danger, H360) for CAS 214766-78-6, indicating reproductive toxicity hazard. Wear nitrile gloves, lab coat, and eye protection. Follow institutional chemical hygiene plans for research peptides and reproductive toxicants.

Storage and Stability

Storage guidance converges on -20C as the standard long-term condition for the lyophilized powder, with desiccation, light protection, and an inert atmosphere. Selleck, InvivoChem, and AbMole specify 3 years at -20C for powder and 2 years at 4C; Szabo Scandic specifies >=2 years at -20C. MedChemExpress offers a more conservative tier of 2 years at -80C and 1 year at -20C, with solutions stable for 6 months at -80C or 1 month at -20C. Selleck states that stability testing supports room-temperature shipping without cooling measures for short transit periods. The -20C condition is the most widely supported archival temperature across the principal suppliers; -80C is the conservative choice for extended storage of either powder or solutions. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening to prevent condensation. Protect from light and moisture throughout storage.

Documentation Support

Per lot: COA, MSDS, certificate of origin, HPLC chromatogram, and mass spectrometry data. Acetate content, water content, peptide content, and salt-form stoichiometry available on request. Custom specifications and third-party inspection can be arranged on a project basis.

About Knowlux

Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.

Compliance Statement

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.

This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. Degarelix Acetate is an approved medicinal product in certain jurisdictions for specific clinical indications (advanced prostate cancer); however, the material offered under this specification is research-grade and is not intended for clinical use. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.

Data Verification Notes

The free peptide molecular formula C82H103ClN18O16 and molecular weight 1632.26 are confirmed by ChemicalBook, Selleck, MedChemExpress, and VWR. The acetate salt molecular formula C84H107ClN18O18 and molecular weight 1692.31 are confirmed by MedChemExpress, InvivoChem, Aobious, and Szabo Scandic. The CAS mapping (214766-78-6 = free peptide; 934016-19-0 = acetate salt; 934246-14-7 = acetate hydrate) is confirmed by ChemicalBook, Selleck, MedChemExpress, InvivoChem, and Pharmaffiliates. The sequence Ac-D-2-Nal-D-4-Cl-Phe-D-3-Pal-Ser-4-Aph(Hor)-4-D-Aph(Cbm)-Leu-Lys(ipr)-Pro-D-Ala-NH2 is confirmed by ChemicalBook and MedChemExpress. The receptor pharmacology constants (IC50 3 nM; pKd 9.2/Kd 0.63 nM; pKi 8.77/Ki 1.7 nM; pIC50 8.06/IC50 8.8 nM; pIC50 8.79/IC50 1.64 nM; pIC50 9.24/IC50 0.58 nM) are from MedChemExpress and the Guide to Pharmacology/ChEMBL curated dataset; the spread is reported as-is because the assays differ in format and readout. The low-histamine-release ranking relative to Cetrorelix, Abarelix, and Ganirelix is from MedChemExpress. Solubility values are reported with their source conditions rather than reconciled into a single figure because the underlying measurements reflect different salt forms, lots, and dissolution techniques. The GHS08 (H360) classification is from ChemicalBook.

Formatting Note: All formulas, sequences, and comparison operators use plain ASCII notation to prevent character corruption on the platform. Section headings, table alignment, and spacing follow the approved product detail pattern. No trailing spaces or non-breaking characters are used; tables use consistent pipe alignment.