生物活性

• 描述Calcium-sensing receptor (CaSR), which belongs to the G protein-coupled receptor superfamily, is responsible for the regulation of systemic Ca²⁺ metabolism. Cinacalcet is a calcimimetic that allosterically increases the sensitivity and responsiveness of CaSR to Ca²⁺. It activates the wild-type CaSR signaling in cellular proliferation and PI hydrolysis assays with pEC50 values of 7.6 and 7.3, respectively^[3]. When primary cultured human parathyroid cells were incubated with 0.5 mM extracellular Ca²⁺, Cinacalcet from 0 – 1000 nM additionally suppressed the secretion of parathyroid hormone at a dose-dependent manner^[4]. Cinacalcet at 30 – 1000 nM had no effect on osteoclastic formation or resorption in osteoclastic cells cultured in calcium-containing medium with the concentration of 1.6 or 6.1 mM^[5]. Oral administration of primary hyperparathyroidism mice with 1 mg/g Cinacalcet for 10 days led to significantly reduced levels of parathyroid and Ca in serum. The uptake of 5-Bromo-2'-deoxyuridine was also significantly decreased in mice following the administration of Cinacalcet compared to the untreated ones^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02464072	Hyperparathyroidism, Secondary	Not Applicable	Active, not recruiting	July 2019	Brazil ... more >> University of Sao Paulo General Hospital Sao Paulo, SP, Brazil Collapse <<
  NCT01073462	-	-	Completed	-	-
  NCT01073462	-	-	Completed	-	Austria ... more >> Site Reference ID/Investigator# 27447 Graz, Austria, 8010 Site Reference ID/Investigator# 49182 Graz, Austria, 8020 Site Reference ID/Investigator# 27483 Graz, Austria, 80360 Site Reference ID/Investigator# 52742 Graz, Austria, 8052 Site Reference ID/Investigator# 27487 Innsbruck, Austria, 6020 Site Reference ID/Investigator# 36983 Linz, Austria, 4010 Site Reference ID/Investigator# 27484 Linz, Austria, 4020 Site Reference ID/Investigator# 27485 Rottenmann, Austria, 8786 Site Reference ID/Investigator# 27446 Vienna, Austria, 1030 Site Reference ID/Investigator# 53469 Vienna, Austria, 1090 Site Reference ID/Investigator# 27482 Vienna, Austria, 1130 Site Reference ID/Investigator# 10981 Vienna, Austria, 1220 Collapse <<

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• 参考文献

• [1] Bushinsky DA, Laplante K, et al. Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. Kidney Int. 2006 May;69(9):1586-92.

  [2] Colloton M, Shatzen E, et al. Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Kidney Int. 2005 Feb;67(2):467-76.

  [3] Ma JN, Owens M, Gustafsson M, Jensen J, Tabatabaei A, Schmelzer K, Olsson R, Burstein ES. Characterization of highly efficacious allosteric agonists of the human calcium-sensing receptor. J Pharmacol Exp Ther. 2011 Apr;337(1):275-84. doi: 10.1124/jpet.110.178194. Epub 2011 Jan 14. PMID: 21239511.

  [4] Kawata T, Imanishi Y, Kobayashi K, Onoda N, Okuno S, Takemoto Y, Komo T, Tahara H, Wada M, Nagano N, Ishimura E, Miki T, Ishikawa T, Inaba M, Nishizawa Y. Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels. J Bone Miner Metab. 2006;24(4):300-6. doi: 10.1007/s00774-006-0687-y. PMID: 16816924.

  [5] Shalhoub V, Grisanti M, Padagas J, Scully S, Rattan A, Qi M, Varnum B, Vezina C, Lacey D, Martin D. In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells. Crit Rev Eukaryot Gene Expr. 2003;13(2-4):89-106. doi: 10.1615/critreveukaryotgeneexpr.v13.i24.30. PMID: 14696958.

  [6] Imanishi Y, Kawata T, Kenko T, Wada M, Nagano N, Miki T, Arnold A, Inaba M. Cinacalcet HCl suppresses Cyclin D1 oncogene-derived parathyroid cell proliferation in a murine model for primary hyperparathyroidism. Calcif Tissue Int. 2011 Jul;89(1):29-35. doi: 10.1007/s00223-011-9490-4. Epub 2011 May 4. PMID: 21541686.

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