Sufugolix-TAK-013-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESufugolixCat. No.: HY-100209CAS No.: 308831-61-0Synonyms: TAK-013分式: CHFNOS分量: 667.72作靶點: Others作通路: Others儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 1.25 mg/mL (1.87 mM; Need ultrason

2、ic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.4976 mL 7.4882 mL 14.9763 mL5 mM - - -10 mM - - -請根據產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 Sufugolix (TAK-013)效有服活性的黃體激素釋放激素 (LHRH) 受體拮抗劑，IC50值為0.1 nM。IC50 & Target IC50: 0.1 nM (human LHRH), 0.6 nM (monkey LHRH) 1體外研究S

3、ufugolix exhibits more than 3- and 2000-fold selectivity for the human receptor over the monkey and ratreceptors, respectively. Sufugolix effectively antagonizes LHRH function on CHO cells expressing the human1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE(IC50=0.1 nM) and monkey (IC50=0.6 nM) rec

4、eptors. During the conformational analysis of sufugolix, usinghigh-temperature molecular dynamics calculation, it is observed that the cis conformer of the methoxyurea ismore populated than the trans conformer 1.體內研究 Oral administration of sufugolix causes almost complete suppression of the plasma L

5、H levels in castratedmale cynomolgus monkeys at a 30 mg/kg dose with sufficient duration of action (more than 24 h). Themaximum plasma concentrations of sufugolix are 0.34 M (reached 6 h after administration) and 0.18 M(reached 4 h after administration) at 30 and 10 mg/kg doses, respectively 1.PROTO

6、COLKinase Assay 1 The receptor-expressing CHO cells are seeded into 24-well plates at a density of 4104 cells/well andcultured for 1 day. The cells are then incubated with 5,6,8,9,11,12,14,15-3Harachidonic acid (11 kBq/well)for 1 day and ished with DMEM supplemented with 20 mM HEPES and 0.2% BSA. Th

7、e cells are thenpreincubated with the compounds (Sufugolix) at 37 C for 60 min and the reaction is started by addition ofLHRH (1 nM). After incubation at37 C for 40 min, radioactivity in the medium is measured with a liquidscintillation counter 1.MCE has not independently confirmed the accuracy of t

8、hese methods. They are for reference only.Animal Monkeys: Sufugolix (10 or 30 mg/kg, 3 mL/kg, n=3 for each group) is suspended in 0.5% methylcelluloseAdministration 1 containing 1.2% citric acid, or 0.5% methylcellulose containing 1.2% citric acid alone (3 mL/kg, n=3), areadministered orally. Blood

9、samples (heparin-plasma) are collected from a femoral vein 24 h beforeadministration and 0, 2, 4, 8, 24, and 48 h after administration. LH concentrations in the plasma aremeasured by bioassays using mouse testicular cells 1.MCE has not independently confirmed the accuracy of these methods. They are

10、for reference only.REFERENCES1. Sasaki S, et al. Discovery of a thieno2,3-dpyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: a highlypotent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor. J Med Chem. 2003Jan 2;46(1):113-24.McePdfHeightCaution: Product has not been fully val