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 Degarelix Acetate

MedKoo Code#:  100255

Name:  Degarelix acetate

CAS#:  214766-78-6 (Degarelix );  934246-14-7 (Degarelix acetate) 　 Synonym:  Code name: FE200486  ||   Chemical structure name: N-acetyl-3-(naphtalen-2-yl)-D-alanyl-4-chloro-D-phenylalanyl-3-(pyridin-3-yl)-D-alanyl-L-seryl-4-((((4S)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-L-leucyl-N6-(1-methylethyl)-L-lysyl-L-prolyl-D-alaninamide.   IUPAC/Chemical name: (S)-N-(4-((2S,5S,8R,11R,14R)-2-(((R)-1-(((S)-1-(((S)-1-((S)-2-(((R)-1-amino-1-oxopropan-2-yl)carbamoyl)pyrrolidin-1-yl)-6-(isopropylamino)-1-oxohexan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)amino)-1-oxo-3-(4-ureidophenyl)propan-2-yl)carbamoyl)-11-(4-chlorobenzyl)-5-(hydroxymethyl)-14-(naphthalen-2-ylmethyl)-4,7,10,13,16-pentaoxo-8-(pyridin-3-ylmethyl)-3,6,9,12,15-pentaazaheptadecyl)phenyl)-2,6-dioxohexahydropyrimidine-4-carboxamide

Chemical structure

Theoretical analysis

Degarelix Chemical Formula: C82H103ClN18O16 Exact Mass: 1630.74880 Molecular Weight: 1632.26 m/z: 1630.74880 (100.0%), 1631.75215 (88.7%), 1632.75551 (38.8%), 1632.74585 (32.0%), 1633.74920 (28.3%), 1634.75256 (12.4%), 1633.75886 (11.2%), 1631.74583 (6.6%), 1632.74919 (5.9%), 1635.75591 (3.6%), 1632.75304 (3.3%), 1633.75640 (2.9%), 1633.75254 (2.6%), 1634.76222 (2.4%), 1633.74288 (2.1%), 1634.74624 (1.9%), 1634.75975 (1.3%), 1631.75507 (1.2%), 1634.75009 (1.1%), 1632.75843 (1.1%) Elemental Analysis: C, 60.34; H, 6.36; Cl, 2.17; N, 15.45; O, 15.68 Degarelix  acetate: Chemical Formula: C84H107ClN18O18 Molecular Weight: 1692.31 Elemental Analysis: C, 59.62; H, 6.37; Cl, 2.09; N, 14.90; O, 17.02

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degarelix is a long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

On 24 December 2008, the Food and Drug Administration (FDA) approved degarelix for the treatment of patients with advanced prostate cancer in the USA.[2] It was subsequently approved by the European Commission at the recommendation of the European Medicines Agency (EMEA) on February 17 2009 for use in adult male patients with advanced, hormone-dependent prostate cancer. Ferring Pharmaceuticals markets the drug under the name Firmagon. From http://en.wikipedia.org/wiki/Degarelix.

Mode of action

GnRH antagonists (receptor blockers) such as degarelix are a new type of hormonal therapy for prostate cancer. These agents are synthetic peptide derivatives of the natural GnRH decapeptide – a hormone that is made by neurons in the hypothalamus. GnRH antagonists compete with natural GnRH for binding to GnRH receptors in the pituitary gland. This reversible blinding blocks the release of LH and FSH from the pituitary. The reduction in LH subsequently leads to a rapid and sustained suppression of testosterone release from the testes and subsequently reduces the size and growth of the prostate cancer. This in turn results in a reduction in prostate-specific antigen (PSA) levels in the patient's blood. Measuring PSA levels is a way to monitor how patients with prostate cancer are responding to treatment. Unlike the GnRH agonists, which cause an initial stimulation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to a surge in testosterone levels, and under certain circumstances, a flare-up of the tumour, GnRH antagonists do not cause a surge in testosterone or clinical flare. Clinical flare is a phenomenon that occurs in patients with advanced disease, which can precipitate a range of clinical symptoms such as bone pain, ureteral obstruction, and spinal cord compression. Drug agencies have issued boxed warnings regarding this phenomenon in the prescribing information for GnRH agonists. As testosterone surge does not occur with GnRH antagonists, there is no need for patients to receive an antiandrogen as flare protection during prostate cancer treatment. GnRH agonists also induce an increase in testosterone levels after each reinjection of the drug – a phenomenon that does not occur with GnRH antagonists such as degarelix.  GnRH antagonists have an immediate onset of action leading to a fast and profound suppression of testosterone and are therefore especially valuable in the treatment of patients with prostate cancer, where fast control of disease is neede. from http://en.wikipedia.org/wiki/Degarelix.

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