Description
NPS-2143 is an antagonist at Ca2+-sensing receptors. It displays anti-osteoporotic, neuroprotective, cardioprotective, and antihypertensive activities. This calcilytic increases bone turnover without decreasing bone mineral density. NPS-2143 also inhibits production of amyloid-β (Aβ) and VEGF and neuronal death in models of Alzheimer’s disease. This compound prevents development of pulmonary arterial hypertension (PAH) and right ventricular hypertrophy in vivo. Additionally, NPS-2143 decreases secretion of CCK, inhibits increases in intracellular Ca2+ levels, and increases secretion of parathyroid hormone (PTH).
References
Dal Prà I, Chiarini A, Pacchiana R, et al. Calcium-Sensing Receptors of Human Astrocyte-Neuron Teams: Amyloid-β-Driven Mediators and Therapeutic Targets of Alzheimer's Disease. Curr Neuropharmacol. 2014 Jul;12(4):353-64. PMID: 25342943.
Dal Prà I, Armato U, Chioffi F, et al. The Aβ peptides-activated calcium-sensing receptor stimulates the production and secretion of vascular endothelial growth factor-A by normoxic adult human cortical astrocytes. Neuromolecular Med. 2014 Dec;16(4):645-57. PMID: 24948534.
Yamamura A. Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension. J Smooth Muscle Res. 2014;50:8-17. PMID: 24770445.
Nakajima S, Hira T, Hara H. Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in enteroendocrine STC-1 cells. Mol Nutr Food Res. 2012 May;56(5):753-60. PMID: 22648622.
Nemeth EF, Delmar EG, Heaton WL, et al. Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther. 2001 Oct;299(1):323-31. PMID: 11561095.
Gowen M, Stroup GB, Dodds RA, et al. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest. 2000 Jun;105(11):1595-604. PMID: 10841518.
