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Details

Stereochemistry ABSOLUTE
Molecular Formula C38H73N21O10S2.ClH
Molecular Weight 1084.712
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETELCALCETIDE HYDROCHLORIDE

SMILES

Cl.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=KHQMSZGKHGQUHG-WZDHWKSBSA-N
InChI=1S/C38H73N21O10S2.ClH/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);1H/t18-,19-,21+,22-,23-,24-,25-,26-;/m1./s1

HIDE SMILES / InChI

Description

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 TargetPharmacologyConditionPotency
25.0 µM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Parsabiv

Cmax

ValueDoseCo-administeredAnalytePopulation
67 ng/mL
0.035 mg/kg single, intravenous
ETELCALCETIDE plasma
Homo sapiens
31.4 ng/mL
0.035 mg/kg single, intravenous
ETELCALCETIDE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2700 ng × h/mL
0.035 mg/kg single, intravenous
ETELCALCETIDE plasma
Homo sapiens
955 ng × h/mL
0.035 mg/kg single, intravenous
ETELCALCETIDE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
5.67 day
0.035 mg/kg single, intravenous
ETELCALCETIDE plasma
Homo sapiens
5.85 h
0.035 mg/kg single, intravenous
ETELCALCETIDE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
12%
unknown, unknown
ETELCALCETIDE plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
 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
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.