Degarelix - GNRH Receptor Antagonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDegarelixCat. No.: HY-16168ACAS No.: 214766-78-6分式: CHClNO分量: 1632.26作靶點: GNRH Receptor作通路: GPCR/G Protein儲存式: Powder -20C 3 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 H2O : 500 mg/mL (306.32 mM)* means soluble, but satu

2、ration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 0.6126 mL 3.0632 mL 6.1265 mL5 mM 0.1225 mL 0.6126 mL 1.2253 mL10 mM 0.0613 mL 0.3063 mL 0.6126 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Degarelix種競爭性，可逆的的促性腺激素釋放激素受體 (GnRHR) 拮抗劑。IC50 & Target GnRHR 1體外研究De

3、garelix acts directly on the pituitary receptors for luteinizing hormone-releasing hormone (LHRH), blockingthe action of endogenous LHRH. The use of degarelix eliminates the initial undesirable surge in gonadotropinand testosterone levels, which is produced by agonists of LHRH 1. Degarelix treatment

4、 reduces cell viability1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEin all prostate cell lines (WPE1-NA22, WPMY-1, BPH-1 cells, VCaP cells), with the exception of the PC-3cells. The GnRH antagonist degarelix exerts a direct effect on prostate cell growth through apoptosis 2.體內(nèi)研究 At single subcut

5、aneous injections of 0.3 to 10 g/kg in rats, degarelix produces a dose-dependentsuppression of the pituitary-gonadal axis as revealed by the decrease in plasma luteinizing hormone (LH)and testosterone levels. Duration of LH suppression increases with the dose: in the rat, significantsuppression of L

6、H lasted 1, 2, and 7 days after a single subcutaneous injection of degarelix at 12.5, 50, or200 g/kg, respectively 3. Degarelix is stable when incubated in microsomes and cryopreservedhepatocytes from animal liver tissue. In rat and dog, most of the degarelix dose is eliminated within 48 h viaurine

7、and feces in equal amounts (4050% in each matrix), whereas in monkey the major route of excretionis fecal (50%) and renal (22%) 4.PROTOCOLCell Assay 2 Cells are allowed to attach for 2448 hours (h). After that, they are treated with different concentrations ofdegarelix, a GnRH antagonist (0.1 to 10

8、M). 10 L of MTT labeling reagent is added to each well and theplates are incubated at 37C for 4h. Then, 100 L of solubilization solution is added, and the plates areincubated at 37C, overnight, in a humidified atmosphere. The final reaction is measured at 550600 nm.The obtained absorbance directly c

9、orrelates to the number of live and metabolically active cells, providing anindication of cell viability 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats: To study the absorption, distribution, metabolism, and excretion, male and female rat

10、s are dosed withAdministration 4 30 g 3Hdegarelix free base peptide/kg (-300 Ci/kg). Feces, heparin plasma, and urine samples fromgroups A and B are collected up to 240 h after dosing. Bile sampling from cannulated rats (group C) as wellas urine and feces are collected for up to 48 h. All samples in

11、 this study are analyzed by LC-RAD at thecontract research 4.Monkeys: Four male cynomolgus Monkeys (4.2-7.5 kg) are dosed for a disposition of radioactivity study. Theanimals are administered a single subcutaneous dose of 8.2 g/kg (200 Ci/kg) 3Hdegarelix. Urine andfeces samples are collected quantit

12、atively from each animal after dosing until the time of sacrifice. Bloodsamples are collected at the time of the sacrifice of the individual animal (6, 24, 48, and 240 h) into tubescontaining EDTA as an anticoagulant 4.MCE has not independently confirmed the accuracy of these methods. They are for r

13、eference only.REFERENCES1. Rick FG, et al. An update on the use of degarelix in the treatment of advanced hormone-dependent prostate cancer. Onco Targets Ther.2013 Apr 16;6:391-402.2. Sakai M, et al. In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonistdegareli

14、x on humanprostate cell growth. PLoS One. 2015 Mar 26;10(3):e0120670.3. Broqua P, et al. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormoneantagonist: degarelix. JPharmacol Exp Ther. 2002 Apr;301(1):95-102.4. Sonesson A, et al. Metabolite profiles of degarelix, a new gonadotropin-releasing hormone receptor antagonist, in rat, dog, and monkey.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEDrug Metab Dispos. 2011 Oct