Identification
- Summary
Etelcalcetide is a calcium sensing receptor agonist used to treat secondary hyperparathyroidism in patients with chronic kidney disease who require hemodialysis.
- Brand Names
- Parsabiv
- Generic Name
- Etelcalcetide
- DrugBank Accession Number
- DB12865
- Background
Etelcalcetide is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis. Etelcalcetide was approved (trade name Parsabiv) for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis in February, 2017.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Etelcalcetide (DB12865)
- Weight
- Average: 1048.26
Monoisotopic: 1047.529069983 - Chemical Formula
- C38H73N21O10S2
- Synonyms
- Etelcalcetida
- Etelcalcetide
- ételcalcétide
- Etelcalcetidum
- Velcalcetide
- External IDs
- AMG-416
- AMG416
- KAI-4169
Pharmacology
- Indication
Etelcalcetide is a calcium-sensing receptor agonist indicated for: Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.
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- Contraindications & Blackbox Warnings
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Following a single intravenous bolus administration of etelcalcetide, PTH levels decreased within 30 minutes post dose. In the single-dose study, the extent and duration of the reduction in PTH increased with increasing dose. Reduction in PTH levels correlated with plasma etelcalcetide concentrations in hemodialysis patients. The reduction in PTH resulted in reductions in calcium and attenuation of post-dialytic phosphate elevation. The effect of reducing PTH levels was maintained throughout the 6-month dosing period when etelcalcetide was administered by intravenous bolus three times a week.
- Mechanism of action
Etelcalcetide is a calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.
Target Actions Organism AExtracellular calcium-sensing receptor agonistHumans - Absorption
The pharmacokinetics of etelcalcetide is linear and does not change over time following single (5 to 60 mg) and multiple intravenous doses (2.5 to 20 mg) in chronic kidney disease patients with secondary hyperparathyroidism requiring hemodialysis. Etelcalcetide exhibited tri-exponential decay following intravenous administration. Based on population pharmacokinetic analysis, following three times a week intravenous dosing at the end of each 3- to 6-hour hemodialysis session in chronic kidney disease patients, etelcalcetide plasma levels reached steady state in 7-8 weeks after dosing with a predicted accumulation ratio of 3- to 4-fold
- Volume of distribution
796 L
- Protein binding
Etelcalcetide is predominately bound to plasma albumin by reversible covalent binding. Non-covalent binding of etelcalcetide to plasma proteins is low with a fraction unbound ratio of 0.53. The ratio of blood-to-plasma [14C]-etelcalcetide concentrations is approximately 0.6.
- Metabolism
Etelcalcetide is not metabolized by CYP450 enzymes. Etelcalcetide is biotransformed in blood by reversible disulfide exchange with endogenous thiols to predominantly form conjugates with serum albumin. Following a single radiolabeled dose of etelcalcetide in chronic kidney disease patients with secondary hyperparathyroidism requiring hemodialysis, the plasma exposure of biotransformation products is approximately 5-fold higher than that of etelcalcetide and their concentration-time course parallels that of etelcalcetide.
- Route of elimination
Etelcalcetide is cleared by renal excretion
- Half-life
3 to 4 days
- Clearance
7.66 L/hr
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
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Ingredient UNII CAS InChI Key Etelcalcetide hydrochloride 72PT5993DU 1334237-71-6 KHQMSZGKHGQUHG-WZDHWKSBSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Parsabiv Injection, solution 5 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU 
Parsabiv Injection, solution 2.5 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU Parsabiv Injection, solution 10 mg/2mL Intravenous AMGEN INC 2017-04-03 Not applicable US 
Parsabiv Injection, solution 10 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU Parsabiv Injection, solution 5 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU Parsabiv Injection, solution 5 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU Parsabiv Injection, solution 2.5 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU Parsabiv Injection, solution 5 mg/1mL Intravenous AMGEN INC 2017-04-03 Not applicable US Parsabiv Injection, solution 10 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU Parsabiv Injection, solution 5 mg Intravenous Amgen Europe B.V. 2020-12-16 Not applicable EU
Categories
- ATC Codes
- H05BX04 — Etelcalcetide
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Oligopeptides
- Alternative Parents
- L-cysteine-S-conjugates / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Alanine and derivatives / L-alpha-amino acids / N-acyl amines / Acetamides / Primary carboxylic acid amides / Guanidines / Dialkyldisulfides show 11 more
- Substituents
- Acetamide / Alanine or derivatives / Aliphatic acyclic compound / Alpha-amino acid / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid / Amino acid or derivatives show 30 more
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 60ME133FJB
- CAS number
- 1262780-97-1
- InChI Key
- ANIAZGVDEUQPRI-ZJQCGQFWSA-N
- InChI
- InChI=1S/C38H73N21O10S2/c1-18(28(62)56-22(27(40)61)8-4-12-49-35(41)42)53-30(64)23(9-5-13-50-36(43)44)58-32(66)25(11-7-15-52-38(47)48)59-31(65)24(10-6-14-51-37(45)46)57-29(63)19(2)54-33(67)26(55-20(3)60)17-71-70-16-21(39)34(68)69/h18-19,21-26H,4-17,39H2,1-3H3,(H2,40,61)(H,53,64)(H,54,67)(H,55,60)(H,56,62)(H,57,63)(H,58,66)(H,59,65)(H,68,69)(H4,41,42,49)(H4,43,44,50)(H4,45,46,51)(H4,47,48,52)/t18-,19-,21+,22-,23-,24-,25-,26-/m1/s1
- IUPAC Name
- (2R)-2-amino-3-{[(2S)-2-{[(1R)-1-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-{[(1R)-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}ethyl]carbamoyl}butyl]carbamoyl}butyl]carbamoyl}butyl]carbamoyl}ethyl]carbamoyl}-2-acetamidoethyl]disulfanyl}propanoic acid
- SMILES
- C[C@@H](NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](C)NC(=O)[C@@H](CSSC[C@H](N)C(O)=O)NC(C)=O)C(=O)N[C@H](CCCNC(N)=N)C(N)=O
References
- General References
- FDA label [Link]
- External Links
- KEGG Drug
- D10676
- PubChem Compound
- 71511839
- PubChem Substance
- 347829023
- ChemSpider
- 32697932
- 1876119
- ChEBI
- 134700
- ChEMBL
- CHEMBL3545184
- Wikipedia
- Etelcalcetide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Chronic Kidney Disease (CKD) / Secondary Hyperparathyroidism (SHPT) 2 3 Completed Treatment Secondary Hyperparathyroidism (SHPT) 5 3 Recruiting Treatment Chronic Kidney Disease (CKD) / Secondary Hyperparathyroidism (SHPT) 1 3 Recruiting Treatment Secondary Hyperparathyroidism (SHPT) 1 2 Completed Diagnostic End Stage Renal Disease (ESRD) 1 2 Completed Treatment Secondary Hyperparathyroidism (SHPT) 2 2 Recruiting Treatment Calcifications, Vascular / Chronic Kidney Disease Mineral and Bone Disorder / Hyperparathyroidism; Secondary, Renal / Renal Osteodystrophy 1 2 Terminated Treatment Secondary Hyperparathyroidism (SHPT) 1 1 Completed Basic Science Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis 1 1 Completed Treatment Secondary Hyperparathyroidism (SHPT) 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 10 mg/2mL Injection, solution Intravenous 10 mg Injection, solution Intravenous 2.5 mg/0.5mL Injection, solution Intravenous 2.5 mg Injection, solution Intravenous 5 mg/1mL Injection, solution Intravenous 5 mg Injection, solution Intravenous; Parenteral 10 MG Injection, solution Intravenous; Parenteral 2.5 MG Injection, solution Intravenous; Parenteral 5 MG Solution Intravenous Injection, solution Intravenous 5 mg/mL Injection, solution 10 mg/2ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8377880 No 2013-02-19 2030-07-29 US US9278995 No 2016-03-08 2030-07-29 US US8999932 No 2015-04-07 2030-07-29 US US9701712 No 2017-07-11 2030-07-29 US US9820938 No 2017-11-21 2034-06-27 US US10344765 No 2019-07-09 2034-06-27 US US11162500 No 2021-11-02 2034-06-27 US
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.132 mg/mL ALOGPS logP -3.4 ALOGPS logP -11 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) -1.3 Chemaxon pKa (Strongest Basic) 12.57 Chemaxon Physiological Charge 4 Chemaxon Hydrogen Acceptor Count 23 Chemaxon Hydrogen Donor Count 22 Chemaxon Polar Surface Area 557.71 Å2 Chemaxon Rotatable Bond Count 36 Chemaxon Refractivity 303.63 m3·mol-1 Chemaxon Polarizability 108.23 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Phosphatidylinositol phospholipase c 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
- Uniprot Name
- Extracellular calcium-sensing receptor
- Molecular Weight
- 120672.385 Da
References
- Martin KJ, Bell G, Pickthorn K, Huang S, Vick A, Hodsman P, Peacock M: Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. Nephrol Dial Transplant. 2014 Feb;29(2):385-92. doi: 10.1093/ndt/gft417. Epub 2013 Nov 13. [Article]
Drug created at October 21, 2016 00:49 / Updated at June 12, 2020 16:53