| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
IC50: 185 nM (hLH) and 46nM (rLH)[1]
Targets the luteinizing hormone receptor (LH-R) with high selectivity. It is species-specific, with reported IC50 values of 185 nM for the human LH-R (hLH) and 46 nM for the rat LH-R (rLH). By acting as an antagonist, it blocks the action of luteinizing hormone, thereby inhibiting the production of downstream sex hormones. |
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| ln Vitro |
Detailed in vitro activity data is limited as this is a direct target-binding antagonist. The key in vitro data is derived from the radioligand binding assays used for its discovery. By blocking the LH receptor, BAY-899 is expected to inhibit LH-induced cAMP production and steroidogenesis (the production of testosterone and estradiol) in Leydig cells (testes) and thecal cells (ovaries).
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| ln Vivo |
In intact female rats, BAY-899 (oral; 12.5 mg/kg/day; for 8 days) effectively lowers blood estradiol levels[1]. The half-lives of BAY-899 (i.v., 0.5 mg/kg or po, 2 mg/kg) are 11 and 12 hours, respectively. Also, the Cmax for IV and PO is 0.24 kg/L and 0.97 kg/L, respectively[1].
BAY-899 demonstrates oral activity in vivo. In intact female rats, oral administration at a dose of 12.5 mg/kg/day for 8 days effectively lowers blood estradiol levels, confirming its ability to block the LH receptor and suppress ovarian steroidogenesis in a living animal. |
| Enzyme Assay |
This is a standard radioligand binding assay for a GPCR. Membranes prepared from cells stably expressing the human or rat LH-R are incubated with a fixed concentration of a high-affinity, radiolabeled ligand (e.g., [¹2⁵I]-human chorionic gonadotropin, hCG, which binds to the LH-R) and increasing concentrations of BAY-899. Bound radioactivity is counted to calculate the IC50 values for the human and rat receptors.
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| Cell Assay |
No specific cell-based assay data is reported. Functional cell-based assays would typically involve measuring cAMP accumulation in LH-R-transfected cells. Cells are pre-incubated with BAY-899 and then stimulated with LH or hCG. The amount of cAMP produced is then measured using an HTRF (Homogeneous Time-Resolved Fluorescence) or ELISA-based kit to confirm the antagonistic effect.
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| Animal Protocol |
Animal/Disease Models: Intact female rats[1]
Doses: 12.5 mg/kg Route of Administration: Oral; for 8 days Experimental Results: demonstrated an efficiency to reduce serum estradiol levels. Animal/Disease Models: Female and male Wistar rats[1] Doses: 0.5 mg/kg of iv or 2 mg/kg of po Route of Administration: Iv or po Experimental Results: Has t1/2s of 11 hrs (hours) and 12 hrs (hours) for iv and po. And the Cmaxs are 0.97 kg/L and 0.24 kg/L for iv and po. In the efficacy study, intact female rats are used to assess the compound's effect on sex hormones. The animals are treated with BAY-899 orally at a dose of 12.5 mg/kg daily for 8 days. At the end of the treatment period, blood samples are collected, and serum estradiol levels are measured by ELISA or a similar immunoassay to quantify the pharmacodynamic effect of the LH receptor antagonist. |
| ADME/Pharmacokinetics |
BAY-899 exhibits favorable pharmacokinetic properties suitable for an oral drug. In female and male Wistar rats, the half-lives (t1/2) of BAY-899 are 11 hours for intravenous (i.v., 0.5 mg/kg) and 12 hours for oral (p.o., 2 mg/kg) administration. The maximum serum concentration (Cmax) is 0.24 kg/L for IV and 0.97 kg/L for PO, with a molecular weight of 459.45.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available. As a compound that potently suppresses sex hormone levels (estradiol in this study), it could cause on-target adverse effects associated with hypogonadism, such as decreased libido, erectile dysfunction, and effects on bone mineral density with long-term use. No acute toxicities are reported for this research compound.
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| References | |
| Additional Infomation |
BAY-899 is a research compound and is not approved for clinical use. It represents a novel, orally active chemical series for antagonizing the LH receptor. This provides a non-hormonal approach to reducing sex hormones, which could have potential applications in treating hormone-sensitive cancers (e.g., breast, prostate), uterine fibroids, or endometriosis.
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| Molecular Formula |
C25H19F2N5O2
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|---|---|
| Molecular Weight |
459.45
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| Exact Mass |
459.15
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| CAS # |
2471967-92-5
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| Related CAS # |
(R)-BAY-899
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| PubChem CID |
139600336
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.657
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| LogP |
2.81
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
664
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN([C@H](C2=C1N=CC=C2)C3=CC=C(C=C3)F)C(=O)NC4=CN=C(N=C4)OC5=CC=C(C=C5)F
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| InChi Key |
VKQBTIMLSDGNLG-QHCPKHFHSA-N
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| InChi Code |
InChI=1S/C25H19F2N5O2/c26-17-5-3-16(4-6-17)23-21-2-1-12-28-22(21)11-13-32(23)25(33)31-19-14-29-24(30-15-19)34-20-9-7-18(27)8-10-20/h1-10,12,14-15,23H,11,13H2,(H,31,33)/t23-/m0/s1
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| Chemical Name |
(5S)-N-[2-(4-fluorophenoxy)pyrimidin-5-yl]-5-(4-fluorophenyl)-7,8-dihydro-5H-1,6-naphthyridine-6-carboxamide
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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) |
DMSO: 130 mg/mL (282.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (7.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.5 mg/mL (7.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3.5 mg/mL (7.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1765 mL | 10.8826 mL | 21.7652 mL | |
| 5 mM | 0.4353 mL | 2.1765 mL | 4.3530 mL | |
| 10 mM | 0.2177 mL | 1.0883 mL | 2.1765 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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