Cinacalcet HCl is the hydrochloride salt of the Type II calcimimetic compound Cinacalcet. Cinacalcet is a modulator of parathyroid hormone secretion. Cinacalcet is able to increase the cytoplasmic concentration of Ca2+. Cinacalcet Hydrochloride is an analog of NPS R-568.
|Mechanism of Action||Cinacalcet is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. It modulates the principal regulator of parathyroid hormone (PTH) secretion, namely the calcium-sensing receptor (CaR) on cells in the parathyroid gland. The CaR becomes more sensitive to extracellular calcium, and this results in a decrease in the level of calcium in serum.|
|Eukaryotic Cell Culture Applications||In vitro studies with Cinacalcet Hydrochloride were done with normal human adult osteoblastic and osteoclastic cells. Authors wanted to understnad wwhether the CaR expressed in these cells, The compound afffected cell proliferation of CHO cells transfected with CaR in dose-dependent manner. Authors also used peripheral blood mononuclear cells supplemented with the compound. The compound had no effect on osteoclastic formation. The calcium-induced increase in osteoblastic cell number involves a mechanism or receptor other than CaR. (Shalhoub et al, 2003). Cinacalcet Hydrochloride increased the concentration of cytoplasmic calcium human embryonic kidney 293 cells expressing the human parathyroid CaR. Similarly, in the presence of 0.5 mM extracellular Ca(2+), Cinacalcet Hydrochloirde (IC50= 28 nM) produced a concentration-dependent decrease in PTH secretion from cultured bovine parathyroid cells. Using rat medullary thyroid carcinoma 6-23 cells expressing CaR, Cinacalcet Hydrochoride (EC50 = 34 nM) produced a concentration-dependent increase in calcitonin secretion. (Nemeth et al, 2004). The inhibitory effect of Cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells removed from excised from parathyroid glands. TPH secretion from cultured cells was suppressed by extracellular Ca2+ and Cinacalcet in a dost-dependent manner (Kawata et al, 2006).|
|References||Howles SA et al (2016) Cinacalcet for symptomatic hypercalcemia caused by AP2S1 mutations. N Eng. J Med 374(14):1396-1398 Kawata, T et al (2006) Direct in vitro evidence of hte suppressive effect of conacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels. J Bone Miner Metab (2006) 24(4): 300-306 Nemeth EF et al (2004) Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. Pharmacol Exp Ther.308(2):627-35. PMID 14593085 Shalhoub V et al (2003) In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells. Crit. Rev. Eukaryot. Gene. Expr. 13(2-4):89-106. PMID 114696958|