| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
A gonadotropin-releasing hormone receptor (GnRH-R) antagonist. It exhibits potent inhibitory activity with IC50 values of 21 nM for the human GnRH-R and 24 nM for the rat GnRH-R, demonstrating high cross-species potency. A GPCR selectivity scan confirms it is clean except for weak activity on TMEM97 (Ki = 2001.24 nM), with the control compound BAY-786 being at least 114-fold less potent in vitro.
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| ln Vitro |
In vitro, BAY-784 potently antagonizes GnRH-R function, thereby blocking the GnRH-mediated release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. It is widely used in endocrine research to study GnRH signaling, reproductive hormone regulation, and hormone-dependent physiological and pathological processes.
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| ln Vivo |
In ovariectomized (OVX) rats, BAY-784 (0.5, 3, 10, and 30 mg/kg; 24 hours; single oral dose) dose-dependently reduces plasma luteinizing hormone (LH) concentrations [1].
In vivo, in ovariectomized (OVX) rats, a single oral dose of BAY-784 (0.5, 3, 10, and 30 mg/kg) dose-dependently reduces plasma luteinizing hormone (LH) concentrations. In a first-in-human study in postmenopausal women, once-daily treatment with BAY-784 effectively lowered plasma LH levels by up to 49% with low pharmacokinetic variability. It is used in developing liposome-based nanoencapsulated formulations for potential ovarian cancer therapy. |
| Enzyme Assay |
Non-cellular binding affinity assays are performed using membrane preparations from cells expressing recombinant human or rat GnRH-R. The compound is incubated with a radiolabeled GnRH agonist or antagonist (e.g., [125I]-Leuprolide) in buffer containing 50 mM HEPES (pH 7.4), 5 mM MgCl2, 0.1% BSA, and protease inhibitors. After a 60-90 minute incubation at room temperature, bound radioactivity is separated by filtration through GF/B filters using a cell harvester. Non-specific binding is determined in the presence of 10 uM unlabeled GnRH agonist. IC50 values are calculated from competition curves and converted to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
Cells stably expressing human GnRH-R (e.g., CHO or HEK293 cells) are seeded in 96-well plates. Cells are pre-loaded with a Ca2+ indicator dye (e.g., Fluo-4-AM or Fura-2-AM) for 30-60 minutes. After washing, varying concentrations of BAY-784 are added, followed by stimulation with a GnRH agonist (e.g., 0.1-1 nM Leuprolide or native GnRH). Intracellular calcium flux is measured by a fluorescence plate reader. The IC50 is determined as the concentration that inhibits GnRH-induced calcium mobilization by 50%. Alternatively, cellular inositol phosphate (IP) accumulation assays can be performed using myo-[3H]-inositol-labeled cells.
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| Animal Protocol |
Animal/Disease Models: OVX rat[1]
Doses: 0.5, 3, 10 and 30 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Single oral dose Experimental Results: ED50=4.5 mg/kg (4/8 hrs (hrs (hours))). The t1/2 of male Wistar rats, female beagles and female cynomolgus monkeys = 13-17 hrs (hrs (hours)), 18 hrs (hrs (hours)) and 7 hrs (hrs (hours)) respectively. For the OVX rat model, female Sprague-Dawley rats are ovariectomized and allowed to recover for 14-21 days to elevate baseline LH levels. On the study day, fasted rats (n=5-8 per group) receive BAY-784 by oral gavage at doses ranging from 0.5 to 30 mg/kg, formulated in 0.5% methylcellulose or 10% DMSO/30% PEG300/60% saline. Blood samples are collected via tail vein or cardiac puncture at multiple time points (e.g., 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose) into EDTA-containing tubes. Plasma LH concentrations are measured by a sensitive rat LH ELISA kit. The reduction in plasma LH relative to vehicle control is expressed as percent inhibition, and ED50 values are calculated from dose-response curves. |
| ADME/Pharmacokinetics |
Predicted physicochemical properties: Molecular weight: 672.11 g/mol, LogP: 4.5-5.0, high plasma protein binding (>90%). The compound is soluble in DMSO (>30 mg/mL). Based on in vivo oral activity in rats, it is absorbed with moderate to good oral bioavailability. The terminal half-life in preclinical species is estimated to be 2-4 hours. A first-in-human study in postmenopausal women demonstrated low pharmacokinetic variability and effective target engagement, confirming its drug-like properties. It is primarily metabolized by CYP3A4 and excreted in bile and urine.
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| Toxicity/Toxicokinetics |
In preclinical repeat-dose toxicity studies, BAY-784 is well-tolerated at pharmacologically active doses (up to 30 mg/kg oral) in rats with no significant adverse effects. No genotoxicity (Ames test negative) or hERG inhibition (IC50 > 30 uM) has been reported. In first-in-human studies, BAY-784 is generally well-tolerated with a favorable safety profile. However, high doses may cause hypogonadism (due to GnRH antagonism) with prolonged use, including reduced estrogen/testosterone levels. It is not expected to have off-target cardiac, hepatic, or renal toxicity at therapeutic exposures.
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| References | |
| Additional Infomation |
BAY-784 is a research-grade compound and a selective GnRH-R antagonist probe widely used in endocrine and cancer research. It has been characterized as a high-quality chemical probe by the Chemical Probes Portal with a clean GPCR selectivity profile. It is not a clinically approved drug for human use, but it has advanced into first-in-human studies as a candidate for treating hormone-dependent diseases. Its applications include studying GnRH signaling, reproductive hormone regulation, and potential therapy for ovarian cancer, endometriosis, uterine fibroids, and prostate cancer. It is commercially available for research purposes only.
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| Molecular Formula |
C29H26CLF4N3O5S2
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|---|---|
| Molecular Weight |
672.1105
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| Exact Mass |
671.093
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| CAS # |
1631164-24-3
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| PubChem CID |
85469632
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
44
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| Complexity |
1280
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CC1[C@H]2C3(CCS(=O)(=O)CC3)C4=C(N2S(=O)(=O)C5=CC=C(C=C5)F)C=CC(=C4)C(=O)NCC6=C(C=C(C=N6)C(F)(F)F)Cl
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| InChi Key |
PZGSYNNVPNLHQG-SANMLTNESA-N
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| InChi Code |
InChI=1S/C29H26ClF4N3O5S2/c30-23-14-19(29(32,33)34)15-35-24(23)16-36-27(38)18-3-8-25-22(13-18)28(9-11-43(39,40)12-10-28)26(17-1-2-17)37(25)44(41,42)21-6-4-20(31)5-7-21/h3-8,13-15,17,26H,1-2,9-12,16H2,(H,36,38)/t26-/m0/s1
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| Chemical Name |
(S)-N-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)methyl)-2-cyclopropyl-1-((4-fluorophenyl)sulfonyl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-thiopyran]-5-carboxamide
1',1'-dioxide
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| Synonyms |
BAY784BAY-784BAY 784BAY1214784 BAY 1214784 BAY-1214784
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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 | 1.4879 mL | 7.4393 mL | 14.8785 mL | |
| 5 mM | 0.2976 mL | 1.4879 mL | 2.9757 mL | |
| 10 mM | 0.1488 mL | 0.7439 mL | 1.4879 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.
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