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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:41:03 UTC
HMDB IDHMDB0015147
Secondary Accession Numbers
  • HMDB15147
Metabolite Identification
Common NameCinacalcet
DescriptionCinacalcet, also known as CNC or mimpara, belongs to the class of organic compounds known as naphthalenes. Naphthalenes are compounds containing a naphthalene moiety, which consists of two fused benzene rings. Cinacalcet is a drug which is used for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease who are on hemodialysis or peritoneal dialysis. also for the treatment of hypercalcemia in patients with parathyroid carcinoma. It is used to treat hyperparathyroidism due to parathyroid tumours or renal failure. Cinacalcet is a very strong basic compound (based on its pKa). Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Cinacalcet is used to treat hyperparathyroidism (elevated parathyroid hormone levels), a consequence of parathyroid tumors and chronic renal failure. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. Metabolism is hepatic by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Cinacalcet is a calcimimetic sold by Amgen under the trade name Sensipar® in North America and Australia and as Mimpara® in Europe.
Structure
Data?1582753263
Synonyms
ValueSource
(R)-alpha-Methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethane amineChEBI
CNCChEBI
MimparaChEBI
N-((1R)-1-(Naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amineChEBI
(R)-a-Methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethane amineGenerator
(R)-Α-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethane amineGenerator
alpha-Methyl-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-naphthalenemethanamine, (alphar)-hydrochlorideHMDB
Hydrochloride, cinacalcetHMDB
SensiparHMDB
073, AMGHMDB
AMG 073HMDB
1493, KRNHMDB
Cinacalcet hydrochlorideHMDB
Chemical FormulaC22H22F3N
Average Molecular Weight357.412
Monoisotopic Molecular Weight357.170434324
IUPAC Name[(1R)-1-(naphthalen-1-yl)ethyl]({3-[3-(trifluoromethyl)phenyl]propyl})amine
Traditional Namecinacalcet
CAS Registry Number226256-56-0
SMILES
C[C@@H](NCCCC1=CC(=CC=C1)C(F)(F)F)C1=CC=CC2=CC=CC=C12
InChI Identifier
InChI=1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1
InChI KeyVDHAWDNDOKGFTD-MRXNPFEDSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as naphthalenes. Naphthalenes are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
KingdomOrganic compounds
Super ClassBenzenoids
ClassNaphthalenes
Sub ClassNot Available
Direct ParentNaphthalenes
Alternative Parents
Substituents
  • Naphthalene
  • Phenylpropylamine
  • Trifluoromethylbenzene
  • Aralkylamine
  • Monocyclic benzene moiety
  • Secondary amine
  • Secondary aliphatic amine
  • Organopnictogen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organic nitrogen compound
  • Alkyl fluoride
  • Amine
  • Alkyl halide
  • Hydrocarbon derivative
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.6e-05 g/LNot Available
LogP6.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.6e-05 g/LALOGPS
logP5.57ALOGPS
logP6.27ChemAxon
logS-6.8ALOGPS
pKa (Strongest Basic)10.3ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity100.12 m³·mol⁻¹ChemAxon
Polarizability37.9 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-1900000000-ff50504d0f6ffef59a7bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0309000000-579cbf32d5eedf61db7aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4r-0914000000-acecef19519978f625eaSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-0900000000-a207a28d48eb7ba6a89dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0109000000-18e95e1ee96e200ba3daSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0219000000-772e71699ff5f6ac691bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fi0-0911000000-4f5a6d4d922a64e42dd5Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01012 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01012 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01012
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID137743
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCinacalcet
METLIN IDNot Available
PubChem Compound156419
PDB IDNot Available
ChEBI ID48390
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
  2. Torres PU: Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease. J Ren Nutr. 2006 Jul;16(3):253-8. [PubMed:16825031 ]
  3. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  2. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  2. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  2. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
General function:
Involved in G-protein coupled receptor activity
Specific function:
Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G- protein that activates a phosphatidylinositol-calcium second messenger system
Gene Name:
CASR
Uniprot ID:
P41180
Molecular weight:
120672.4
References
  1. de Francisco AL: Cinacalcet HCl: a novel therapeutic for hyperparathyroidism. Expert Opin Pharmacother. 2005 Mar;6(3):441-52. [PubMed:15794735 ]
  2. Rothe HM, Shapiro WB, Sun WY, Chou SY: Calcium-sensing receptor gene polymorphism Arg990Gly and its possible effect on response to cinacalcet HCl. Pharmacogenet Genomics. 2005 Jan;15(1):29-34. [PubMed:15864123 ]
  3. Tasic V: Management of renal osteodystrophy in children. Turk J Pediatr. 2005;47 Suppl:13-8. [PubMed:15884662 ]
  4. Moe SM, Cunningham J, Bommer J, Adler S, Rosansky SJ, Urena-Torres P, Albizem MB, Guo MD, Zani VJ, Goodman WG, Sprague SM: Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl. Nephrol Dial Transplant. 2005 Oct;20(10):2186-93. Epub 2005 Jul 19. [PubMed:16030053 ]
  5. Cunningham J: Management of secondary hyperparathyroidism. Ther Apher Dial. 2005 Aug;9 Suppl 1:S35-40. [PubMed:16109140 ]
  6. Eriguchi R, Umakoshi J, Tominaga Y, Sato Y: Successful treatment of inoperable recurrent secondary hyperparathyroidism with cinacalcet HCl. NDT Plus. 2008 Aug;1(4):218-220. Epub 2008 May 25. [PubMed:19461861 ]
  7. Belozeroff V, Goodman WG, Ren L, Kalantar-Zadeh K: Cinacalcet lowers serum alkaline phosphatase in maintenance hemodialysis patients. Clin J Am Soc Nephrol. 2009 Mar;4(3):673-9. doi: 10.2215/CJN.03790808. Epub 2009 Mar 4. [PubMed:19261825 ]
  8. Meola M, Petrucci I, Barsotti G: Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism. Nephrol Dial Transplant. 2009 Mar;24(3):982-9. doi: 10.1093/ndt/gfn654. Epub 2009 Jan 30. [PubMed:19181759 ]
  9. Drueke TB, Ritz E: Treatment of secondary hyperparathyroidism in CKD patients with cinacalcet and/or vitamin D derivatives. Clin J Am Soc Nephrol. 2009 Jan;4(1):234-41. doi: 10.2215/CJN.04520908. Epub 2008 Dec 3. [PubMed:19056615 ]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]