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Chemical Compound Review

Parareg     N-[(1R)-1-naphthalen-1- ylethyl]-3-[3...

Synonyms: Cinacalcet, AMG-073, SureCN71876, AMG073, CHEMBL1201284, ...
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Disease relevance of AMG 073


High impact information on AMG 073


Chemical compound and disease context of AMG 073


Biological context of AMG 073


Anatomical context of AMG 073

  • Calcium (greater than 6.0 mM) inhibited osteoclast formation, but cinacalcet HCl (30-1000 nM) had no effect on osteoclastic formation or resorption in the presence of calcium (1.6 or 6.1 mM) [13].
  • Using rat medullary thyroid carcinoma 6-23 cells expressing the CaR, cinacalcet HCl (EC(50) = 34 nM) produced a concentration-dependent increase in calcitonin secretion [15].
  • Cinacalcet modulates the calcium-sensing receptor on the parathyroid gland to reduce secretion of parathyroid hormone and lower serum calcium, phosphorus and calcium-phosphorus product in haemodialysis patients [16].

Associations of AMG 073 with other chemical compounds

  • However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed [4].
  • Notably, cinacalcet HCl proved effective in a broad range of CKD patients on dialysis with uncontrolled secondary HPT, regardless of disease severity, duration of dialysis treatment, dialysis modality, race, age, gender, or concurrent phosphate binder or vitamin D sterol use [17].
  • METHODS: Cinacalcet HCl (10 or 1 mg/kg, p.o. gavage), 1,25-dihydroxyvitamin D(3) (0.1 microg, s.c, calcitriol) or the combination was administered daily for 26 days in a rat model of secondary HPT [5/6 nephrectomy] [18].
  • Clinical trials have documented that the calcimimetic agent cinacalcet hydrochloride effectively lowers plasma PTH levels without increasing serum calcium or phosphorus concentrations in adult hemodialysis patients with SHPT [19].
  • SELECTION CRITERIA: We included all RCTs of any calcimimetic agent, cinacalcet HCl (AMG-073, Sensipar), NPS R-467 or NPS R-568 administered to patients with CKD for the treatment of SHPT [20].

Gene context of AMG 073


Analytical, diagnostic and therapeutic context of AMG 073


  1. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. Quarles, L.D., Sherrard, D.J., Adler, S., Rosansky, S.J., McCary, L.C., Liu, W., Turner, S.A., Bushinsky, D.A. J. Am. Soc. Nephrol. (2003) [Pubmed]
  2. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. Lindberg, J.S., Culleton, B., Wong, G., Borah, M.F., Clark, R.V., Shapiro, W.B., Roger, S.D., Husserl, F.E., Klassen, P.S., Guo, M.D., Albizem, M.B., Coburn, J.W. J. Am. Soc. Nephrol. (2005) [Pubmed]
  3. Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. Peacock, M., Bilezikian, J.P., Klassen, P.S., Guo, M.D., Turner, S.A., Shoback, D. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  4. Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism. Szwarc, I., Argilés, A., Garrigue, V., Delmas, S., Chong, G., Deleuze, S., Mourad, G. Transplantation (2006) [Pubmed]
  5. Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Colloton, M., Shatzen, E., Miller, G., Stehman-Breen, C., Wada, M., Lacey, D., Martin, D. Kidney Int. (2005) [Pubmed]
  6. Cinacalcet in the management of tumor-induced osteomalacia. Geller, J.L., Khosravi, A., Kelly, M.H., Riminucci, M., Adams, J.S., Collins, M.T. J. Bone Miner. Res. (2007) [Pubmed]
  7. Keynote review: allosterism in membrane receptors. Gao, Z.G., Jacobson, K.A. Drug Discov. Today (2006) [Pubmed]
  8. First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl. Martin, K.J., Jüppner, H., Sherrard, D.J., Goodman, W.G., Kaplan, M.R., Nassar, G., Campbell, P., Curzi, M., Charytan, C., McCary, L.C., Guo, M.D., Turner, S.A., Bushinsky, D.A. Kidney Int. (2005) [Pubmed]
  9. No effect of renal function or dialysis on pharmacokinetics of cinacalcet (Sensipar/Mimpara). Padhi, D., Harris, R.Z., Salfi, M., Sullivan, J.T. Clinical pharmacokinetics. (2005) [Pubmed]
  10. Vitamin D analogs for secondary hyperparathyroidism: What does the future hold? Brown, A.J. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  11. Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride. Sloand, J.A., Shelly, M.A. Am. J. Kidney Dis. (2006) [Pubmed]
  12. Therapeutic strategies for secondary hyperparathyroidism in dialysis patients. Ogata, H., Koiwa, F., Ito, H., Kinugasa, E. Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. (2006) [Pubmed]
  13. In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells. Shalhoub, V., Grisanti, M., Padagas, J., Scully, S., Rattan, A., Qi, M., Varnum, B., Vezina, C., Lacey, D., Martin, D. Crit. Rev. Eukaryot. Gene Expr. (2003) [Pubmed]
  14. Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients. Serra, A.L., Savoca, R., Huber, A.R., Hepp, U., Delsignore, A., Hersberger, M., Wüthrich, R.P. Nephrol. Dial. Transplant. (2007) [Pubmed]
  15. Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. Nemeth, E.F., Heaton, W.H., Miller, M., Fox, J., Balandrin, M.F., Van Wagenen, B.C., Colloton, M., Karbon, W., Scherrer, J., Shatzen, E., Rishton, G., Scully, S., Qi, M., Harris, R., Lacey, D., Martin, D. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  16. Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl. Moe, S.M., Cunningham, J., Bommer, J., Adler, S., Rosansky, S.J., Urena-Torres, P., Albizem, M.B., Guo, M.D., Zani, V.J., Goodman, W.G., Sprague, S.M. Nephrol. Dial. Transplant. (2005) [Pubmed]
  17. Cinacalcet hydrochloride. Barman Balfour, J.A., Scott, L.J. Drugs (2005) [Pubmed]
  18. 1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism. Henley, C., Colloton, M., Cattley, R.C., Shatzen, E., Towler, D.A., Lacey, D., Martin, D. Nephrol. Dial. Transplant. (2005) [Pubmed]
  19. Calcimimetic agents and secondary hyperparathyroidism: rationale for use and results from clinical trials. Goodman, W.G. Pediatr. Nephrol. (2003) [Pubmed]
  20. 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]
  21. 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. 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. J. Bone Miner. Metab. (2006) [Pubmed]
  22. Calcium-sensing receptor gene polymorphism Arg990Gly and its possible effect on response to cinacalcet HCl. Rothe, H.M., Shapiro, W.B., Sun, W.Y., Chou, S.Y. Pharmacogenet. Genomics (2005) [Pubmed]
  23. Extracellular calcium-sensing receptors in the parathyroid gland, kidney, and other tissues. Quarles, L.D. Curr. Opin. Nephrol. Hypertens. (2003) [Pubmed]
  24. Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Harris, R.Z., Salfi, M., Posvar, E., Hoelscher, D., Padhi, D. Eur. J. Clin. Pharmacol. (2007) [Pubmed]
  25. The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. Goodman, W.G., Hladik, G.A., Turner, S.A., Blaisdell, P.W., Goodkin, D.A., Liu, W., Barri, Y.M., Cohen, R.M., Coburn, J.W. J. Am. Soc. Nephrol. (2002) [Pubmed]
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