Sufugolix (TAK-013) is a potent and orally available luteinizing hormone-releasing hormone (LHRH) receptor antagonist.

LHRH:0.1 nM.

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

Oral administration of sufugolix at a 30 mg/kg dose causes almost complete suppression of plasma LH levels in castrated male cynomolgus monkeys for more than 24 hours. Sufugolix exhibits sufficient lipophilicity for enhanced membrane permeability and improved oral absorption in monkeys. Maximum plasma concentrations are 0.34 μM (6 hours post-administration) and 0.18 μM (4 hours post-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].