Sufugolix 是一种高效的、有口服活性的黄体激素释放激素 (LHRH) 受体拮抗剂(IC50:0.1 nM)。

TAK-013 is a potent and orally available luteinizing hormone-releasing hormone LHRH receptor.

Sufugolix exhibits more than 3- and 2000-fold selectivity for the human receptor over the monkey and rat receptors, respectively. Sufugolix effectively antagonizes LHRH function on CHO cells expressing the human (IC50=0.1 nM) and monkey (IC50=0.6 nM) receptors. It is observed that the cis conformer of the methoxyurea is more populated than the trans conformer by high-temperature molecular dynamics calculation during the conformational analysis of sufugolix[1].

Oral administration of sufugolix causes almost complete suppression of the plasma LH levels in castrated male cynomolgus monkeys at a 30 mg/kg dose with sufficient duration of action (more than 24 h). Sufugolix has the apparent lipophilicity to allow increased membrane permeability and consequently improve its oral absorption in monkeys. The maximum plasma concentrations of sufugolix are 0.34 μM (reached 6 h after administration) and 0.18 μM (reached 4 h after administration) at 30 and 10 mg/kg doses, respectively[1].

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].

308831-61-0

C36H31F2N5O4S

667.72

TAK-013

DMSO:10mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years