| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
NBI-42902 targets the human gonadotropin-releasing hormone (GnRH) receptor. It acts as a potent, functional, and competitive antagonist. It binds to the receptor with high affinity, with a Ki of 0.56 nM and an IC50 of 0.79 nM. Tritiated NBI-42902 binds with a Kd of 0.19 nM to a single class of binding sites. By blocking the GnRH receptor, it inhibits the release of gonadotropins (LH and FSH) from the pituitary gland.
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| ln Vitro |
NBI-42902 (0-1000 nM) inhibits GnRH receptors with IC50 values of 0.79 nM (human), 10 nM (cynomolgus monkey), 400 nM (dog), and 200 nM. It is extremely sensitive to differences in incubation sequence between species. With an average IC50 value of 3.6 nM, (NBI-42902 (1 nM-1 μM, 1 min) suppresses the Ca2+ fields generated by GnRH (4 nM) in RBL cells[1]. Rabbit NBI-42902 [1]. IP accumulation in RBL cells caused by GnRH (4 nM) is competitively inhibited by nM-1 μM, 1 min [1]. With an IC50 value of 5.22 nM, NBI-42902 (1 nM-1 μM, 5 minutes) totally inhibits GnRH-stimulated ERK1/2 phosphorylation in CHO-GnRHR cells[1].
In vitro, NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor. It demonstrates competitive antagonism, inhibiting GnRH-stimulated IP accumulation, Ca²⁺ flux, and ERK1/2 activation. Its high affinity (Ki = 0.56 nM) and potent functional antagonism make it a valuable tool for studying GnRH receptor signaling. It is also orally active, making it suitable for in vivo studies. |
| ln Vivo |
In female macaque monkeys, NBI-42902 (10-100 mg/kg, lateral or intravenous injection) dramatically suppresses blood LH levels [1].
In vivo, NBI-42902 is an orally active antagonist of the GnRH receptor. By inhibiting the GnRH receptor, it suppresses the hypothalamic-pituitary-gonadal axis, leading to a decrease in the production of sex hormones. This makes it a potential therapeutic agent for conditions such as hormone-sensitive cancers, endometriosis, and uterine fibroids. Its oral bioavailability is a key advantage over peptide-based GnRH antagonists. |
| Enzyme Assay |
The in vitro affinity of NBI-42902 for the GnRH receptor is determined using radioligand binding assays. In a cell-free protocol, membranes from cells expressing the human GnRH receptor are incubated with a radiolabeled ligand (e.g., [³H]-NBI-42902) and varying concentrations of unlabeled competitors. The amount of bound radioligand is measured, and the Ki is calculated.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: CHO-GnRHR Tested Concentrations: 1 nM-1 μM Incubation Duration: 5 min Experimental Results: Blocked GnRH (1 nM)-completely stimulates ERK1/2 phosphorylation in a dose-dependent manner with an IC50 value of 5.22 nM. Cellular assays for NBI-42902 involve studying its effect on GnRH receptor-mediated signaling. In a typical protocol, cells expressing the GnRH receptor are loaded with a calcium-sensitive fluorescent dye or a reporter for IP accumulation. Stimulation with GnRH leads to an increase in intracellular calcium or IP production. NBI-42902 is pre-incubated with the cells, and its ability to inhibit the GnRH-induced response is measured. |
| Animal Protocol |
Animal/Disease Models: Castrated macaques [1]
Doses: 10, 40, 100 mg/kg Route of Administration: oral (po) Experimental Results: Inhibition of serum LH in a dose-dependent manner. Suppressed serum LH reached maximum suppression at 4-8 hrs (hrs (hours)) after dosing, which was 62-68% of pre-treatment baseline. LH levels demonstrated no suppression after 24 h of treatment with 10 or 40 mg/kg but remained suppressed at 100 mg/kg. Animal/Disease Models: Castrated macaques [1] Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: 4-8 hrs (hrs (hours)) after administration, serum LH reached maximum suppression, which was 62-68% of the baseline before treatment. However, no inhibition was shown after administration. 24 hrs (hrs (hours)). The in vivo efficacy of NBI-42902 can be evaluated in animal models. In a typical protocol, the compound is administered orally to rodents. The effect on the hypothalamic-pituitary-gonadal axis is assessed by measuring serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormones (e.g., testosterone, estradiol). The compound's ability to suppress these hormone levels is a measure of its in vivo activity. |
| ADME/Pharmacokinetics |
NBI-42902 is an orally active, small-molecule GnRH receptor antagonist. It has a molecular weight of 455.52 and a molecular formula of C₂₅H₂₅F₂N₅O₂. Its oral bioavailability makes it a promising candidate for therapeutic development. Detailed pharmacokinetic parameters (e.g., half-life, Cmax) would be characterized in preclinical studies, but are not typically reported in the public domain for this research compound.
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| Toxicity/Toxicokinetics |
The toxicity of NBI-42902 would be assessed in standard preclinical toxicology studies. As a GnRH receptor antagonist, its primary effects are related to the suppression of the hypothalamic-pituitary-gonadal axis, which can lead to a reduction in sex hormone levels. This can have various physiological effects, including on bone density and reproductive function. These effects would be carefully evaluated during drug development.
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| References | |
| Additional Infomation |
NBI-42902 is a potent, orally active, nonpeptide antagonist of the human GnRH receptor. It has a high affinity for the receptor, with a Ki of 0.56 nM. It is a competitive antagonist that inhibits GnRH-stimulated IP accumulation, Ca²⁺ flux, and ERK1/2 activation. It has potential as an oral drug for suppressing the hypothalamic-pituitary-gonadal axis and is a significant compound in endocrinology research.
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| Molecular Formula |
C27H24F3N3O3
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| Molecular Weight |
495.492977142334
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| Exact Mass |
495.176
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| CAS # |
352290-60-9
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| PubChem CID |
11167850
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
631.0±65.0 °C at 760 mmHg
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| Flash Point |
335.4±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.602
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| LogP |
6.42
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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 |
7
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| Heavy Atom Count |
36
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| Complexity |
824
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C(=O)N(C(=O)N1CC2=C(C=CC=C2F)F)C[C@@H](C3=CC=CC=C3)N)C4=C(C(=CC=C4)OC)F
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| InChi Key |
CJUWBZDJMYYRDG-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C27H24F3N3O3/c1-16-24(18-10-6-13-23(36-2)25(18)30)26(34)33(15-22(31)17-8-4-3-5-9-17)27(35)32(16)14-19-20(28)11-7-12-21(19)29/h3-13,22H,14-15,31H2,1-2H3/t22-/m0/s1
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| Chemical Name |
3-[(2R)-2-amino-2-phenylethyl]-1-[(2,6-difluorophenyl)methyl]-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidine-2,4-dione
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| Synonyms |
NBI42902, NBI-42902, NBI 42902
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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 | 2.0182 mL | 10.0910 mL | 20.1820 mL | |
| 5 mM | 0.4036 mL | 2.0182 mL | 4.0364 mL | |
| 10 mM | 0.2018 mL | 1.0091 mL | 2.0182 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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