Sufugolix (TAK-013)

A gonadotropin-releasing hormone receptor antagonist

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5mg

￥1075.00

860.00

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10mg

￥1775.00

1420.00

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25mg

￥3900.00

3120.00

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50mg

￥7000.00

5600.00

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100mg

￥12287.00

9830.00

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货号: ajce49040
CAS: 308831-61-0
别名: TAK-013
分子式: C36H31F2N5O4S
分子量: 667.72
纯度: >98%
溶解度: DMSO : 1.25 mg/mL (1.87 mM)
储存: Store at -20°C,unstable in solution, ready to use.
库存: 现货

Background

Sufugolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist (IC₅₀ = 0.1 nM).¹ Sufugolix inhibits GnRH-induced arachidonic acid release in CHO cells expressing human recombinant or monkey recombinant GnRH (IC₅₀s = 0.1 and 10 nM, respectively), but not the rat GnRH receptor. It inhibits luteinizing hormone (LH) release stimulated by GnRH in monkey pituitary cells ex vivo (IC₅₀ = 36 nM).² Sufugolix (10 and 30 mg/kg) reduces increases in plasma LH following castration in male cynomolgus monkeys and lowers serum LH, estradiol, and progesterone levels in female cynomolgus monkeys when administered at a dose of 90 mg/kg.^1,2

1.Sasaki, S., Cho, N., Nara, Y., et al.Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: A highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptorJ. Med. Chem.46(1)113-124(2003) 2.Hara, T., Araki, H., Kusaka, M., et al.Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeysJ. Clin. Endocrinol. Metab.88(4)1697-1704(2003)

Protocol

Kinase experiment:

The receptor-expressing CHO cells are seeded into 24-well plates at a density of 4×104 cells/well and cultured for 1 day. The cells are then incubated with [5,6,8,9,11,12,14,15-3H]arachidonic acid (11 kBq/well) for 1 day and ished with DMEM supplemented with 20 mM HEPES and 0.2% BSA. The cells are then preincubated with the compounds (Sufugolix) at 37 °C for 60 min and the reaction is started by addition of LHRH (1 nM). After incubation at37 °C for 40 min, radioactivity in the medium is measured with a liquid scintillation counter[1].

Animal experiment:

Monkeys: Sufugolix (10 or 30 mg/kg, 3 mL/kg, n=3 for each group) is suspended in 0.5% methylcellulose containing 1.2% citric acid, or 0.5% methylcellulose containing 1.2% citric acid alone (3 mL/kg, n=3), are administered orally. Blood samples (heparin-plasma) are collected from a femoral vein 24 h before administration and 0, 2, 4, 8, 24, and 48 h after administration. LH concentrations in the plasma are measured by bioassays using mouse testicular cells[1].

参考文献:

[1]. Sasaki S, et al. Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: a highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor. J Med Chem. 2003 Jan 2;46(1):113-24.