CAS 183552-38-7 Abarelix

Abarelix Chemical Properties

Boiling point 1688.4±65.0 °C(Predicted)

density 1.286±0.06 g/cm3(Predicted)

pka 9.82±0.15(Predicted)

Safety Information

MSDS Information

Abarelix Usage And Synthesis

Description Abarelix is an antagonist of the gonadotropin releasing-hormone (Gn RH) receptor, and it was launched as an intramuscular injection for the palliative treatment of advanced symptomatic prostate cancer. Hormonal therapy of prostate cancer is based on the modulation of testosterone to achieve medical castration levels. The inhibition of GnRH activity causes the suppression of luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion, thereby reducing the secretion of testosterone by the testes. Abarelix is the first GnRH antagonist to reach its market. Hormonal therapy with GnRH agonists such as leuprolide, buserelin, and goserelin has been in use for over two decades. Drugs of this type achieve the suppression of LH and FSH by a feedback inhibition mechanism, which involves an initial rise in the LH and FSH levels and, consequently, in the levels of testosterone. A testosterone surge may induce a clinical tumor flare that worsens cancer-related symptoms. This phenomenon is observed in 4–33% of patients receiving a GnRH agonist. A GnRH antagonist such as abarelix acts by direct inhibition of LH and FSH secretion, which avoids the initial surge in serum testosterone concentrations. Abarelix is a decapeptide, and it is prepared by a typical coupling cycle for peptide synthesis using Boc-amino acids and a methylbenzhydrylamine (MBHA) resin. Abarelix has high binding affinity for GnRH receptor (Kd=0.1 nM). Following intramuscular administration of a 100 mg dose, abarelix is absorbed slowly with a Cmax of 43.4 ng/mL observed approximately 3 days after the injection and has a half-life of about 13 days. The apparent volume of distribution is over 4000 L, suggesting extensive distribution. Abarelix has high protein binding (96–99%), and it is primarily metabolized via hydrolysis