Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C38H73N21O10S2 |
Molecular Weight | 1048.251 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
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
InChI
InChIKey=ANIAZGVDEUQPRI-ZJQCGQFWSA-N
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
Molecular Formula | C38H73N21O10S2 |
Molecular Weight | 1048.251 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Etelcalcetide (formerly velcalcetide, trade name Parsabiv) 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. Etelcalcetide is a synthetic peptide calcium-sensing receptor agonist. It 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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1878 |
25.0 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Parsabiv Approved UsePARSABIV is a calcium-sensing receptor agonist indicated for:
Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney
disease (CKD) on hemodialysis. Launch Date2017 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
67 ng/mL |
0.035 mg/kg single, intravenous dose: 0.035 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ETELCALCETIDE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: UNKNOWN food status: UNKNOWN |
|
31.4 ng/mL |
0.035 mg/kg single, intravenous dose: 0.035 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ETELCALCETIDE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2700 ng × h/mL |
0.035 mg/kg single, intravenous dose: 0.035 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ETELCALCETIDE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: UNKNOWN food status: UNKNOWN |
|
955 ng × h/mL |
0.035 mg/kg single, intravenous dose: 0.035 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ETELCALCETIDE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.67 day |
0.035 mg/kg single, intravenous dose: 0.035 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ETELCALCETIDE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: UNKNOWN food status: UNKNOWN |
|
5.85 h |
0.035 mg/kg single, intravenous dose: 0.035 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ETELCALCETIDE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12% |
unknown, unknown |
ETELCALCETIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
45 mg multiple, intravenous (total weekly dose) Studied dose Dose: 45 mg Route: intravenous Route: multiple Dose: 45 mg Sources: |
unhealthy, 61 ± 14 years Health Status: unhealthy Age Group: 61 ± 14 years Sex: M+F Sources: |
|
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Disc. AE: Calcium decreased, Nausea... AEs leading to discontinuation/dose reduction: Calcium decreased (5 patients) Sources: Page: p. 30Nausea (1 patient) Vomiting (1 patient) Chest discomfort (1 patient) GI malformation (1 patient) Hemiparesis (1 patient) Hyperhidrosis (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Chest discomfort | 1 patient Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
GI malformation | 1 patient Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Hemiparesis | 1 patient Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Hyperhidrosis | 1 patient Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Nausea | 1 patient Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Vomiting | 1 patient Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Calcium decreased | 5 patients Disc. AE |
5 mg 3 times / week steady, intravenous Recommended Dose: 5 mg, 3 times / week Route: intravenous Route: steady Dose: 5 mg, 3 times / week Sources: Page: p. 30 |
unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: Page: p. 30 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=44 Page: 33.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Etelcalcetide (AMG 416), a peptide agonist of the calcium-sensing receptor, preserved cortical bone structure and bone strength in subtotal nephrectomized rats with established secondary hyperparathyroidism. | 2017 Dec |
|
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism. | 2017 Jul |
|
Formulary Drug Review: Etelcalcetide. | 2017 Nov |
|
Etelcalcetide: injectable calcimimetic for the treatment of secondary hyperparathyroidism in hemodialysis-dependent patients. | 2017 Sep |
|
A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet. | 2018 May |
Patents
Sample Use Guides
Ensure corrected serum calcium is at or above the lower limit of normal prior to PARSABIV (Etelcalcetide) initiation, a PARSABIV dose increase, or re-initiation of PARSABIV therapy after a dosing interruption.
The recommended starting dose of PARSABIV is 5 mg administered by intravenous (IV) bolus injection
three times per week at the end of hemodialysis treatment.
The maintenance dose of PARSABIV is individualized and determined by titration based on parathyroid
hormone (PTH) and corrected serum calcium response. The maintenance dose is the dose that maintains PTH levels within the recommended target range and corrected
serum calcium within the normal range. The lowest maintenance dose of PARSABIV is 2.5 mg three times
per week and the highest maintenance dose of PARSABIV is 15 mg three times per week.
Administer PARSABIV only at the end of hemodialysis treatment.
If a regularly scheduled hemodialysis treatment is missed, DO NOT administer any missed doses. Resume
PARSABIV at the end of the next hemodialysis treatment at the prescribed dose. If doses of PARSABIV are
missed for more than 2 weeks, re-initiate PARSABIV at the recommended starting dose of 5 mg (or 2.5 mg
if that was the patient’s last dose).
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23674604
Treatment of HEK-293T cells expressing the
hCaSR with increasing concentrations of Etelcalcetide (AMG 416) resulted in
a dose-dependent increase in IP1 accumulation with an
apparent EC50 of 25 uM.
Substance Class |
Chemical
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60ME133FJB
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C78275
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567616
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N0000175902
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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BINDER->LIGAND |
Etelcalcetide is primarily bound to plasma albumin and the plasma non-covalent protein binding is less than 50%.
BINDING
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TARGET -> AGONIST |
Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE LESS ACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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