NBI-42902
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 201980

CAS#: 352290-60-9

Description: NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor (K(i) = 0.56 nm). Tritiated NBI-42902 binds with high affinity (K(d) = 0.19 nm) to a single class of binding sites and can be displaced by a range of peptide and nonpeptide GnRH receptor ligands. In vitro experiments demonstrate that NBI-42902 is a potent functional, competitive antagonist of GnRH stimulated IP accumulation, Ca(2+) flux, and ERK1/2 activation. It did not stimulate histamine release from rat peritoneal mast cells. Finally, it is effective in lowering serum LH in castrated male macaques after oral administration. Overall, these data provide a benchmark of pharmacological characteristics required for a nonpeptide GnRH antagonist to effectively suppress gonadotropins in humans and suggest that NBI-42902 may have clinical utility as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis. (source: Endocrinology. 2007 Feb;148(2):857-67. Epub 2006 Nov 9.)


Chemical Structure

img
NBI-42902
CAS# 352290-60-9

Theoretical Analysis

MedKoo Cat#: 201980
Name: NBI-42902
CAS#: 352290-60-9
Chemical Formula: C27H24F3N3O3
Exact Mass: 495.18
Molecular Weight: 495.490
Elemental Analysis: C, 65.45; H, 4.88; F, 11.50; N, 8.48; O, 9.69

Price and Availability

Size Price Availability Quantity
5mg USD 650 2 Weeks
Bulk inquiry

Synonym: NBI42902, NBI-42902, NBI 42902

IUPAC/Chemical Name: 3-[(2R)-Amino-2-phenylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidin-2,4-dione

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

SMILES Code: O=C1N(C[C@H](N)C2=CC=CC=C2)C(C(C3=CC=CC(OC)=C3F)=C(C)N1CC4=C(F)C=CC=C4F)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:       

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 495.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Tello JA, Newton CL, Bouligand J, Guiochon-Mantel A, Millar RP, Young J. Congenital hypogonadotropic hypogonadism due to GnRH receptor mutations in three brothers reveal sites affecting conformation and coupling. PLoS One. 2012;7(6):e38456. doi: 10.1371/journal.pone.0038456. Epub 2012 Jun 5. PubMed PMID: 22679506; PubMed Central PMCID: PMC3367945.

2: Sullivan SK, Brown MS, Gao Y, Loweth CJ, Lio FM, Crowe PD, Struthers RS, Betz SF. Allosteric and orthosteric binding modes of two nonpeptide human gonadotropin-releasing hormone receptor antagonists. Biochemistry. 2006 Dec 26;45(51):15327-37. Epub 2006 Dec 1. PubMed PMID: 17176055.

3: Struthers RS, Xie Q, Sullivan SK, Reinhart GJ, Kohout TA, Zhu YF, Chen C, Liu XJ, Ling N, Yang W, Maki RA, Bonneville AK, Chen TK, Bozigian HP. Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902. Endocrinology. 2007 Feb;148(2):857-67. Epub 2006 Nov 9. PubMed PMID: 17095587.

4: Sullivan SK, Hoare SR, Fleck BA, Zhu YF, Heise CE, Struthers RS, Crowe PD. Kinetics of nonpeptide antagonist binding to the human gonadotropin-releasing hormone receptor: Implications for structure-activity relationships and insurmountable antagonism. Biochem Pharmacol. 2006 Sep 28;72(7):838-49. Epub 2006 Aug 22. PubMed PMID: 16930559.

5: Struthers RS, Chen T, Campbell B, Jimenez R, Pan H, Yen SS, Bozigian HP. Suppression of serum luteinizing hormone in postmenopausal women by an orally administered nonpeptide antagonist of the gonadotropin-releasing hormone receptor (NBI-42902). J Clin Endocrinol Metab. 2006 Oct;91(10):3903-7. Epub 2006 Jul 18. PubMed PMID: 16849403.

6: Ayabe T. [An outline of GnRH analogue]. Nihon Rinsho. 2006 Apr;64 Suppl 4:64-9. Review. Japanese. PubMed PMID: 16689286.

7: Betz SF, Reinhart GJ, Lio FM, Chen C, Struthers RS. Overlapping, nonidentical binding sites of different classes of nonpeptide antagonists for the human gonadotropin-releasing hormone receptor. J Med Chem. 2006 Jan 26;49(2):637-47. PubMed PMID: 16420049.

8: Tucci FC, Hu T, Mesleh MF, Bokser A, Allsopp E, Gross TD, Guo Z, Zhu YF, Struthers RS, Ling N, Chen C. Atropisomeric property of 1-(2,6-difluorobenzyl)-3-[(2R)-amino-2-phenethyl]-5-(2-fluoro-3-methoxyphenyl)-6- methyluracil. Chirality. 2005 Nov;17(9):559-64. PubMed PMID: 16196024.

9: Tucci FC, Zhu YF, Struthers RS, Guo Z, Gross TD, Rowbottom MW, Acevedo O, Gao Y, Saunders J, Xie Q, Reinhart GJ, Liu XJ, Ling N, Bonneville AK, Chen T, Bozigian H, Chen C. 3-[(2R)-Amino-2-phenylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)- 6-methylpyrimidin-2,4-dione (NBI 42902) as a potent and orally active antagonist of the human gonadotropin-releasing hormone receptor. Design, synthesis, and in vitro and in vivo characterization. J Med Chem. 2005 Feb 24;48(4):1169-78. PubMed PMID: 15715483.