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^[1][2]. IC50 & Target: IC50: 43 nM (Ca²⁺ receptor) In Vitro: NPS-2143 (SB-262470A) 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^[1].
In HEK 293 cells transiently expressing hCaSRs, NPS-2143 significantly suppresses the kokumi taste by effectively inhibiting the activity of both GSH and γ-Glu-Val-Gly^[3]. 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^[4]. In Vivo: NPS-2143 (SB-262470A) results in a rapid 4- to 5-fold increase in plasma PTH levels in rats^[1].
In normotensive rats, NPS-2143 administration (1 mg/kg, i.v.) markedly increases mean arterial blood pressure (MAP) in the presence of parathyroid glands^[2].