NPS-2143

NPS-2143 (SB-262470A), an orally active calcilytic agent, is a selective and potent calcium ion-sensing receptor (CaSR) antagonist. NPS-2143 (SB-262470A) blocks increases in cytoplasmic Ca2+ concentrations (IC50=43 nM) elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor.

Product information

CAS Number: 284035-33-2

Molecular Weight: 408.92

Formula: C24H25ClN2O2

Synonym:

SB-262470A

Related CAS Number:

324523-20-8 (NPS-2143 hydrochloride)

Chemical Name: 2-chloro-6-[(2R)-2-hydroxy-3-{[2-methyl-1-(naphthalen-2-yl)propan-2-yl]amino}propoxy]benzonitrile

Smiles: CC(C)(CC1C=C2C=CC=CC2=CC=1)NC[C@@H](O)COC1=CC=CC(Cl)=C1C#N

InChiKey: PZUJQWHTIRWCID-HXUWFJFHSA-N

InChi: InChI=1S/C24H25ClN2O2/c1-24(2,13-17-10-11-18-6-3-4-7-19(18)12-17)27-15-20(28)16-29-23-9-5-8-22(25)21(23)14-26/h3-12,20,27-28H,13,15-16H2,1-2H3/t20-/m1/s1

Technical Data

Appearance: Solid Power

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

Solubility: DMSO 82 mg/mL (200.53 mM) Water Insoluble

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

NPS 2143 blocks increases in cytoplasmic Ca2+ concentrations with IC50 of 43 nM elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. NPS 2143 stimulates parathyroid hormone (PTH) secretion from bovine parathyroid cells with EC50 of 41 nM. Moreover, NPS 214 also blocks the inhibitory effects of calcimimetic NPS R-467 on PTH secretion from bovine parathyroid cells and the inhibitory effects of extracellular Ca2+ on isoproterenol-stimulated increases in cyclic AMP formation. In HEK-293 cells transiently expressing hCaSRs, NPS 2143 significantly suppresses the kokumi taste by effectively inhibiting the activity of both GSH (data not shown) and γ-Glu-Val-Gly. A recent study shows that NPS 2143 treatment suppresses low molecular weight fractions of azuki hydrolysate-induced cholecystokinin (CCK) secretion in CaSR-transfected HEK 293 cells.

In Vivo:

In rats, NPS 2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase in plasma Ca2+ levels. In normotensive rats, NPS 2143 administration (1 mg/kg) by i.v. markedly increases mean arterial blood pressure (MAP) in the presence of parathyroid glands.

References:

1. Nemeth EF, et al. J Pharmacol Exp Ther. 2001, 299(1), 323-331.
2. Rybczynska A, et al. J Endocrinol. 2006, 191(1), 189-195.
3. Ohsu T, et al. J Biol Chem. 2010, 285(2), 1016-1022.
4. Nakajima S, et al. Mol Nutr Food Res. 2012, 56(5), 753-760.

Products are for research use only. Not for human use.