NBI-42902 (NBI 42902; NBI42902) is a novel and potent peptide radioligand/inhibitor/antagonist of GnRH receptor with the potential to be used as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis. It binds to the human GnRH receptor with a Ki of 0.56 nm.
Physicochemical Properties
| Molecular Formula | C27H24F3N3O3 |
| Molecular Weight | 495.492977142334 |
| Exact Mass | 495.176 |
| CAS # | 352290-60-9 |
| PubChem CID | 11167850 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 631.0±65.0 °C at 760 mmHg |
| Flash Point | 335.4±34.3 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.602 |
| LogP | 6.42 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 36 |
| Complexity | 824 |
| Defined Atom Stereocenter Count | 1 |
| 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 |
| InChi Key | CJUWBZDJMYYRDG-QFIPXVFZSA-N |
| 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 |
| Chemical Name | 3-[(2R)-2-amino-2-phenylethyl]-1-[(2,6-difluorophenyl)methyl]-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidine-2,4-dione |
| Synonyms | NBI42902, NBI-42902, NBI 42902 |
| 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) |
Biological Activity
| 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]. |
| ln Vivo | In female macaque monkeys, NBI-42902 (10-100 mg/kg, lateral or intravenous injection) dramatically suppresses blood LH levels [1]. |
| 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. |
| 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)). |
| References |
[1]. Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902. Endocrinology. 2007 Feb;148(2):857-67. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |