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Chemical Compound Review

Norcalcin     3-(2-chlorophenyl)-N-[(1R)-1- (3...

Synonyms: Tecalcet HCl, NPS-R-568, Norcalcin (TN), KRN-568, CHEMBL2107572, ...
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Disease relevance of NPS R 568


High impact information on NPS R 568

  • Treatment of these same cells with a calcimimetic, NPS-R-568, augments the CaSR response to Ca(2+), increasing phosphatidylinositol turnover and ERK1/2 phosphorylation, and overcoming the autoantibody effects [5].
  • NPS R-568 potentiated the effects of extracellular Ca2+ on [Ca2+]i and PTH secretion but was without effect in the absence of extracellular Ca2+ [6].
  • Both NPS R-467 and NPS R-568 increased [Ca2+]i in HEK 293 cells expressing the human parathyroid Ca2+ receptor but were without effect in wild-type HEK 293 cells [6].
  • In a study on experimental animals, the results clearly showed that this first generation of calcimimetics, NPS R-568, had an acute dose-dependent and short-lived suppressive effect on PTH secretion from the parathyroid glands [2].
  • NPS R-568 rescued expression of loss-of-function CaR mutants, increasing plasma membrane expression and ERK1/2 phosphorylation in response to 5 mm Ca(2+) [7].

Chemical compound and disease context of NPS R 568

  • NPS R-568 decreased plasma Ca(2+) levels in thyroidectomized parathyroid-intact rats, but the rate of onset of hypocalcemia was slower than in controls [8].

Biological context of NPS R 568


Anatomical context of NPS R 568


Associations of NPS R 568 with other chemical compounds


Gene context of NPS R 568

  • The calcimimetic NPS R-568 decreases plasma PTH in rats with mild and severe renal or dietary secondary hyperparathyroidism [16].
  • When secondary HPT had developed, NPS R-568 was administered and blood samples were collected for up to 6 h [16].
  • CONCLUSION: These results demonstrate that the calcimimetic compound NPS R-568 can prevent both the increase in serum PTH levels and parathyroid hyperplasia in rats with CRI and severe secondary HPT [12].
  • NPS R-568 rapidly increased plasma calcitonin levels to a peak at 10 to 20 min after oral dosing (ED(50) 40 mg/kg) [8].
  • Fetal rat metatarsal bones (dpc 20) were cultured in serum-free medium for 7 days in the presence or absence of NPS-R-568, a CaR agonist [14].

Analytical, diagnostic and therapeutic context of NPS R 568


  1. The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor. Wada, M., Furuya, Y., Sakiyama, J., Kobayashi, N., Miyata, S., Ishii, H., Nagano, N. J. Clin. Invest. (1997) [Pubmed]
  2. Prevention of uremic bone disease using calcimimetic compounds. Olgaard, K., Lewin, E. Annu. Rev. Med. (2001) [Pubmed]
  3. Activation of the calcium receptor by a calcimimetic compound halts the progression of secondary hyperparathyroidism in uremic rats. Chin, J., Miller, S.C., Wada, M., Nagano, N., Nemeth, E.F., Fox, J. J. Am. Soc. Nephrol. (2000) [Pubmed]
  4. Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism. Nagano, N. Pharmacol. Ther. (2006) [Pubmed]
  5. An acquired hypocalciuric hypercalcemia autoantibody induces allosteric transition among active human Ca-sensing receptor conformations. Makita, N., Sato, J., Manaka, K., Shoji, Y., Oishi, A., Hashimoto, M., Fujita, T., Iiri, T. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  6. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Nemeth, E.F., Steffey, M.E., Hammerland, L.G., Hung, B.C., Van Wagenen, B.C., DelMar, E.G., Balandrin, M.F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Rescue of Calcium-sensing Receptor Mutants by Allosteric Modulators Reveals a Conformational Checkpoint in Receptor Biogenesis. Huang, Y., Breitwieser, G.E. J. Biol. Chem. (2007) [Pubmed]
  8. Calcimimetic compound NPS R-568 stimulates calcitonin secretion but selectively targets parathyroid gland Ca(2+) receptor in rats. Fox, J., Lowe, S.H., Conklin, R.L., Petty, B.A., Nemeth, E.F. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  9. Calcium sensing receptor activation by a calcimimetic suggests a link between cooperativity and intracellular calcium oscillations. Miedlich, S., Gama, L., Breitwieser, G.E. J. Biol. Chem. (2002) [Pubmed]
  10. NPS R-568: a type II calcimimetic compound that acts on parathyroid cell calcium receptor of rats to reduce plasma levels of parathyroid hormone and calcium. Fox, J., Lowe, S.H., Petty, B.A., Nemeth, E.F. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  11. Hypertensive effect of calcilytic NPS 2143 administration in rats. Rybczynska, A., Lehmann, A., Jurska-Jasko, A., Boblewski, K., Orlewska, C., Foks, H., Drewnowska, K. J. Endocrinol. (2006) [Pubmed]
  12. Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. Wada, M., Nagano, N., Furuya, Y., Chin, J., Nemeth, E.F., Fox, J. Kidney Int. (2000) [Pubmed]
  13. A novel calcium sensor stimulating inositol phosphate formation and [Ca2+]i signaling expressed by GCT23 osteoclast-like cells. Seuwen, K., Boddeke, H.G., Migliaccio, S., Perez, M., Taranta, A., Teti, A. Proc. Assoc. Am. Physicians (1999) [Pubmed]
  14. Effects of Ca2+ sensing receptor activation in the growth plate. Wu, S., Palese, T., Mishra, O.P., Delivoria-Papadopoulos, M., De Luca, F. FASEB J. (2004) [Pubmed]
  15. Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients. Strippoli, G.F., Tong, A., Palmer, S.C., Elder, G., Craig, J.C. Cochrane database of systematic reviews (Online) (2006) [Pubmed]
  16. The calcimimetic NPS R-568 decreases plasma PTH in rats with mild and severe renal or dietary secondary hyperparathyroidism. Fox, J., Lowe, S.H., Conklin, R.L., Nemeth, E.F. Endocrine (1999) [Pubmed]
  17. A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication. Antonsen, J.E., Sherrard, D.J., Andress, D.L. Kidney Int. (1998) [Pubmed]
  18. The calcium receptor and calcimimetics. Wada, M., Nagano, N., Nemeth, E.F. Curr. Opin. Nephrol. Hypertens. (1999) [Pubmed]
  19. Pharmacological activity of calcimimetic NPS R-568 administered intravenously in rats: dose dependency. Rybczyńska, A., Boblewski, K., Lehmann, A., Orlewska, C., Foks, H. Pharmacological reports : PR. (2006) [Pubmed]
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