Synonym
Sufugolix; TAK-013; TAK013; TAK 013.
IUPAC/Chemical Name
1-(4-(5-((benzyl(methyl)amino)methyl)-1-(2,6-difluorobenzyl)-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-3-methoxyurea
InChi Key
UCQSBGOFELXYIN-UHFFFAOYSA-N
InChi Code
InChI=1S/C36H31F2N5O4S/c1-41(20-23-10-5-3-6-11-23)21-28-31-33(44)43(26-12-7-4-8-13-26)36(46)42(22-27-29(37)14-9-15-30(27)38)34(31)48-32(28)24-16-18-25(19-17-24)39-35(45)40-47-2/h3-19H,20-22H2,1-2H3,(H2,39,40,45)
SMILES Code
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
Appearance
Yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Sufugolix is a LHRH receptor antagonist with an IC50 of 0.1 nM.
In vitro activity:
Sufugolix is an insurmountable GnRH receptor antagonist, more effective at blocking the human receptor (hGnRHR) than the macaque receptor (mGnRHR). Additionally, mutating Met-24 in hGnRHR abolishes sufugolix's insurmountable activity. This suggests a model where specific receptor regions prolong sufugolix's binding, enhancing its insurmountable effect.
Reference: Mol Pharmacol. 2007 Aug;72(2):238-47. https://pubmed.ncbi.nlm.nih.gov/17409285/
In vivo activity:
Sufugolix holds promise for treating reproductive disorders and for assisting reproductive technology procedures. Sufugolix effectively suppressed LH release in cynomolgus monkeys at concentrations above 100 nM, with an IC(50) value of 36 nM. Chronic oral administration of sufugolix continued to suppress LH, estradiol, and progesterone levels in female cynomolgus monkeys, but not FSH, with reversible effects upon discontinuation. This suppressive effect was not observed in marmoset monkeys.
Reference: J Clin Endocrinol Metab. 2003 Apr;88(4):1697-704. https://pubmed.ncbi.nlm.nih.gov/12679460/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.0 |
29.95 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
667.73
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kohout TA, Xie Q, Reijmers S, Finn KJ, Guo Z, Zhu YF, Struthers RS. Trapping of a nonpeptide ligand by the extracellular domains of the gonadotropin-releasing hormone receptor results in insurmountable antagonism. Mol Pharmacol. 2007 Aug;72(2):238-47. doi: 10.1124/mol.107.035535. Epub 2007 Apr 4. PMID: 17409285.
2. Nakata D, Masaki T, Tanaka A, Yoshimatsu M, Akinaga Y, Asada M, Sasada R, Takeyama M, Miwa K, Watanabe T, Kusaka M. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice. Eur J Pharmacol. 2014 Jan 15;723:167-74. doi: 10.1016/j.ejphar.2013.12.001. Epub 2013 Dec 11. PMID: 24333551.
3. Hara T, Araki H, Kusaka M, Harada M, Cho N, Suzuki N, Furuya S, Fujino M. Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys. J Clin Endocrinol Metab. 2003 Apr;88(4):1697-704. doi: 10.1210/jc.2002-021065. PMID: 12679460.
In vitro protocol:
1. Kohout TA, Xie Q, Reijmers S, Finn KJ, Guo Z, Zhu YF, Struthers RS. Trapping of a nonpeptide ligand by the extracellular domains of the gonadotropin-releasing hormone receptor results in insurmountable antagonism. Mol Pharmacol. 2007 Aug;72(2):238-47. doi: 10.1124/mol.107.035535. Epub 2007 Apr 4. PMID: 17409285.
In vivo protocol:
1. Nakata D, Masaki T, Tanaka A, Yoshimatsu M, Akinaga Y, Asada M, Sasada R, Takeyama M, Miwa K, Watanabe T, Kusaka M. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice. Eur J Pharmacol. 2014 Jan 15;723:167-74. doi: 10.1016/j.ejphar.2013.12.001. Epub 2013 Dec 11. PMID: 24333551.
2. Hara T, Araki H, Kusaka M, Harada M, Cho N, Suzuki N, Furuya S, Fujino M. Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys. J Clin Endocrinol Metab. 2003 Apr;88(4):1697-704. doi: 10.1210/jc.2002-021065. PMID: 12679460.
Szkudlinski MW. Challenges and opportunities of trapping ligands. Mol Pharmacol. 2007 Aug;72(2):231-4. doi: 10.1124/mol.107.038208. Epub 2007 May 23. PMID: 17522183.
Miwa K, Hitaka T, Imada T, Sasaki S, Yoshimatsu M, Kusaka M, Tanaka A, Nakata D, Furuya S, Endo S, Hamamura K, Kitazaki T. Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor. J Med Chem. 2011 Jul 28;54(14):4998-5012. doi: 10.1021/jm200216q. Epub 2011 Jun 23. PMID: 21657270.
Alves VM, Bobrowski T, Melo-Filho CC, Korn D, Auerbach S, Schmitt C, Muratov EN, Tropsha A. QSAR Modeling of SARS-CoV Mpro Inhibitors Identifies Sufugolix, Cenicriviroc, Proglumetacin, and other Drugs as Candidates for Repurposing against SARS-CoV-2. Mol Inform. 2021 Jan;40(1):e2000113. doi: 10.1002/minf.202000113. Epub 2020 Aug 24. PMID: 33405340.
