Sufugolix

SKU: orb1225350

Description

Sufugolix (TAK-013) is a highly potent and orally bioavailable non-peptide antagonist of luteinizing hormone-releasing hormone (LHRH) receptor with binding and functional IC50 of 0.1 and 0.06 nM for human LHRH, respectively; completely suppresses plasma LH levels in castrated male cynomolgus monkeys at 30 mg/kg dose with sufficient duration of action (>24 h)(In Vitro):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. During the conformational analysis of sufugolix, using high-temperature molecular dynamics calculation, it is observed that the cis conformer of the methoxyurea is more populated than the trans conformer .(In Vivo):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). 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.

Key Properties

• CAS Number: 308831-61-0
• MW: 667.7242
• Purity: >98% (HPLC)
• Formula: C₃₆H₃₁F₂N₅O₄S
• SMILES: O=C(NOC)NC1=CC=C(C(S2)=C(CN(C)CC3=CC=CC=C3)C(C(N4C5=CC=CC=C5)=O)=C2N(CC6=C(F)C=CC=C6F)C4=O)C=C1
• Target: LHR
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  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). 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.
• In Vitro:
  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. During the conformational analysis of sufugolix, using high-temperature molecular dynamics calculation, it is observed that the cis conformer of the methoxyurea is more populated than the trans conformer.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TAK013 | TAK-013 | TAK 013

Quick Database Links

Gene Symbol

LHR