| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 1g | |||
| Other Sizes |
| Targets |
GnRH receptor (gonadotropin-releasing hormone receptor). Opigolix is an orally active, small-molecule, non-peptide GnRH receptor antagonist. GnRH receptors are G protein-coupled receptors that regulate the release of gonadotropins (luteinizing hormone and follicle-stimulating hormone) from the pituitary gland. By antagonizing the GnRH receptor, Opigolix suppresses gonadotropin release, thereby reducing the production of sex hormones such as estrogen and testosterone. This mechanism is effective in treating sex-hormone-dependent conditions, including endometriosis, uterine fibroids, prostate cancer, and rheumatoid arthritis. Opigolix was under clinical development by Astellas Pharma for the management of these conditions. However, development was discontinued in 2018.
|
|---|---|
| ln Vitro |
GnRH receptor antagonist Opigolix (compound 726) is utilized in the investigation of illnesses dependent on sex hormones, particularly those connected to GnRH [1].
Opigolix is a GnRH receptor antagonist that suppresses gonadotropin release and reduces sex hormone production. The compound's activity has been characterized in receptor binding assays and functional assays measuring gonadotropin release. Opigolix is an orally active, small-molecule, non-peptide antagonist. The compound was being developed for the treatment of endometriosis-associated pain, rheumatoid arthritis, and uterine fibroids. In clinical studies, 15 mg Opigolix was approximately equivalent to 400 mg elagolix, enabling direct cross-compound pharmacodynamic comparisons. The compound is a fluorinated small molecule suitable as a reference standard for LC-MS/MS method development and metabolic stability profiling. |
| ln Vivo |
Opigolix has been evaluated in vivo in clinical trials. The compound is an orally active GnRH receptor antagonist that was under clinical development by Astellas Pharma. It was being investigated for the management of sex-hormone-dependent conditions, primarily endometriosis-associated pain and rheumatoid arthritis. In clinical studies, 15 mg Opigolix was approximately equivalent to 400 mg elagolix in terms of pharmacodynamic effects. The compound completed Phase II clinical trials before development was discontinued globally in 2018. Detailed clinical trial data are available from published studies. Opigolix is for research use only and is not for human therapeutic use.
|
| Enzyme Assay |
GnRH receptor binding assays are performed using membranes prepared from cells expressing recombinant GnRH receptors. Radioligand binding studies use [¹²⁵I]- or [³H]-labeled GnRH analogs as labeled ligands. Membrane preparations are incubated with varying concentrations of Opigolix and a fixed concentration of radioligand in binding buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl₂, 0.1% BSA) for 60-120 minutes at room temperature. Non-specific binding is determined using excess unlabeled GnRH or a GnRH antagonist. Bound radioactivity is measured by scintillation or gamma counting after filtration. IC50 and Ki values are calculated by non-linear regression. Functional assays measure inhibition of gonadotropin release from pituitary cells or cell lines.
|
| Cell Assay |
Cellular GnRH receptor antagonism is evaluated in cell lines expressing GnRH receptors (e.g., αT3-1 or LβT2 cells) or in primary pituitary cells. Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with Opigolix at various concentrations. GnRH-induced gonadotropin (LH and FSH) release is measured by ELISA or RIA. The compound's antagonist activity is assessed by its ability to inhibit GnRH-induced gonadotropin release. Cell viability is assessed using MTT or LDH assays. Each experiment includes known GnRH antagonists as positive controls and vehicle controls.
|
| Animal Protocol |
In vivo efficacy of Opigolix was evaluated in clinical trials for endometriosis-associated pain and other sex-hormone-dependent conditions. The compound was administered orally at doses determined by clinical study protocols. In clinical studies, 15 mg Opigolix was approximately equivalent to 400 mg elagolix in terms of pharmacodynamic effects. The compound completed Phase II clinical trials before development was discontinued globally in 2018. Endpoints included reduction in endometriosis-associated pain, changes in sex hormone levels, and safety assessments. Sample sizes in clinical trials typically range from 100-300 patients per group.
|
| ADME/Pharmacokinetics |
Molecular Weight: 544.50. Formula: C25H19F3N4O5S. CAS No.: 912587-25-8. IUPAC Name: (2R)-N-{5-[3-(2,5-difluorophenyl)-2-(2,3-dihydro-1H-1,3-benzodiazol-2-ylidene)-1,3-dioxopropyl]-2-fluorophenyl}sulfonyl-2-hydroxypropanimidamide. Synonyms: ASP-1707. Appearance: Solid powder. Purity: Typically ≥98%. Solubility: Soluble in DMSO. Storage: Dry, dark, 0-4°C for short term, -20°C for long term. Opigolix is an orally active, small-molecule GnRH receptor antagonist.
|
| Toxicity/Toxicokinetics |
Opigolix has been evaluated in clinical trials for safety and efficacy. The compound was generally well-tolerated at therapeutic doses. Common adverse effects may include hot flashes, headache, nausea, and other effects related to sex hormone suppression. Development of Opigolix was discontinued globally in 2018 following the completion of Phase II clinical trials. The compound is for research use only and is not for human therapeutic use.
|
| References | |
| Additional Infomation |
Opigolix is also known as ASP-1707. Its IUPAC name is (2R)-N-{5-[3-(2,5-difluorophenyl)-2-(2,3-dihydro-1H-1,3-benzodiazol-2-ylidene)-1,3-dioxopropyl]-2-fluorophenyl}sulfonyl-2-hydroxypropanimidamide. Opigolix is an orally active, small-molecule, non-peptide GnRH receptor antagonist. It was under clinical development by Astellas Pharma for endometriosis-associated pain, rheumatoid arthritis, and uterine fibroids. Development was discontinued in 2018. No regulatory approvals have been reported. Opigolix is for research use only.
|
| Molecular Formula |
C25H19F3N4O5S
|
|---|---|
| Molecular Weight |
544.502374887466
|
| Exact Mass |
544.102
|
| CAS # |
912587-25-8
|
| PubChem CID |
135565248
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
706.9±70.0 °C at 760 mmHg
|
| Flash Point |
381.3±35.7 °C
|
| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
| Index of Refraction |
1.665
|
| LogP |
0.45
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
38
|
| Complexity |
1050
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O=C(C1=CC(S(NC([C@H](O)C)=N)(=O)=O)=C(F)C=C1)/C(C(C2=C(C=CC(F)=C2)F)=O)=C3NC4=CC=CC=C4N\3
|
| InChi Key |
QLLWADSMMMNRDJ-AFRFTAIISA-N
|
| InChi Code |
InChI=1S/C25H19F3N4O5S/c1-12(33)24(29)32-38(36,37)20-10-13(6-8-17(20)28)22(34)21(23(35)15-11-14(26)7-9-16(15)27)25-30-18-4-2-3-5-19(18)31-25/h2-12,33-34H,1H3,(H2,29,32)(H,30,31)/b22-21+/t12-/m1/s1
|
| Chemical Name |
(2R)-N'-[5-[(Z)-2-(1H-benzimidazol-2-yl)-3-(2,5-difluorophenyl)-1-hydroxy-3-oxoprop-1-enyl]-2-fluorophenyl]sulfonyl-2-hydroxypropanimidamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8365 mL | 9.1827 mL | 18.3655 mL | |
| 5 mM | 0.3673 mL | 1.8365 mL | 3.6731 mL | |
| 10 mM | 0.1837 mL | 0.9183 mL | 1.8365 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
