ETELCALCETIDE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C38H73N21O10S2.ClH
Molecular Weight	1084.7155
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of ETELCALCETIDE HYDROCHLORIDE

Structure Search

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
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208325Orig1s000Lbledt.pdf

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
Calcium sensing receptor 10 Target ID: CHEMBL1878 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208325Orig1s000Lbledt.pdf	Agonist 2752		25.0 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis 2 Sources: http://www.parsabiv.com/	Primary		Approved 8583	Parsabiv Approved Use PARSABIV is a calcium-sensing receptor agonist indicated for: Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Launch Date 2017

C_max

Value	Dose	Co-administered	Analyte	Population
67 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/variation-report/parsabiv-h-c-3995-p46-002-epar-assessment-report_en.pdf	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 OTHER GOV https://www.ema.europa.eu/en/documents/variation-report/parsabiv-h-c-3995-p46-002-epar-assessment-report_en.pdf	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 OTHER GOV https://www.ema.europa.eu/en/documents/variation-report/parsabiv-h-c-3995-p46-002-epar-assessment-report_en.pdf	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 OTHER GOV https://www.ema.europa.eu/en/documents/variation-report/parsabiv-h-c-3995-p46-002-epar-assessment-report_en.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.67 day OTHER GOV https://www.ema.europa.eu/en/documents/variation-report/parsabiv-h-c-3995-p46-002-epar-assessment-report_en.pdf	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 OTHER GOV https://www.ema.europa.eu/en/documents/variation-report/parsabiv-h-c-3995-p46-002-epar-assessment-report_en.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
12% REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf	unknown, unknown		ETELCALCETIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
45 mg multiple, intravenous Studied dose Dose: 45 mg Route: intravenous Route: multiple Dose: 45 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31330805/	unhealthy, 61 ± 14 years Health Status: unhealthy Age Group: 61 ± 14 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/31330805/	Sources: https://pubmed.ncbi.nlm.nih.gov/31330805/
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	Disc. AE: Calcium decreased, Nausea... AEs leading to discontinuation/dose reduction: Calcium decreased (5 patients) Nausea (1 patient) Vomiting (1 patient) Chest discomfort (1 patient) GI malformation (1 patient) Hemiparesis (1 patient) Hyperhidrosis (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf

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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 OAT1 725 OAT3 747 OCT2 779 OATP1B1 1079 OATP1B2 6 PEPT1 27 PEPT2 13 BSEP 550 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060	P-gp 2052 BCRP 697 OAT1 395 OAT3 391 OCT2 434 OATP1B1 503 OATP1B2 7 PEPT1 60 PEPT2 37 BSEP 63 P450 3	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 55, (ClinPharm) 7, 26	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 54-55, (ClinPharm) 7, 26	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, (ClinPharm) 7, 26	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 54-55, (ClinPharm) 7, 26	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, (ClinPharm) 7, 26	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, (ClinPharm) 7, 26	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 54-55, (ClinPharm) 7, 26	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B2 6	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
PEPT1 29	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
PEPT2 17	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000ClinPharmR.pdf#page=8 Page: 7, 26	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B2 7	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
P450 3	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=57 Page: 46-48, 52-53, (ClinPharm) 7, 26	no
PEPT1 60	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
PEPT2 37	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=44 Page: 33.0

Sourcing

Vendor/Aggregator	ID	URL
Ambeed	A592953	https://www.ambeed.com/products/1262780-97-1.html
Chem Scene	CS-0030931	http://www.chemscene.com/1262780-97-1.html
Chemenu	CM100712	http://www.chemenu.com/products/CM100712
Chemspace	CSSB00161190358	https://chem-space.com/CSSB00161190358
DC Chemicals	DC8189	http://www.dcchemicals.com/product_show-Etelcalcetide_Hydrochloride_AMG_416_.html
eNovation Chemicals	D674080	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674080
MedChem Express	HY-P1955	https://www.medchemexpress.com/etelcalcetide.html
MolPort	MolPort-046-782-741	https://www.molport.com/shop/molecule-link/MolPort-046-782-741
MuseChem	I006723	https://www.musechem.com/product/I006723.html
Smolecule	S527486	http://www.smolecule.com/products/s527486
THE BioTek	bt-242394	https://www.thebiotek.com/product/peptides/bt-242394
THE BioTek	bt-267793	https://www.thebiotek.com/product/inhibitors/bt-267793

PubMed

Title	Date	PubMed
A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.	2018-05	29392552
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.	2017-12	28867373
Formulary Drug Review: Etelcalcetide.	2017-11	29276237
Etelcalcetide: injectable calcimimetic for the treatment of secondary hyperparathyroidism in hemodialysis-dependent patients.	2017-09	29238762
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism.	2017-07	29142982

Patents

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.

Name

Type

Language

AMG 416

Preferred Name

English

ETELCALCETIDE HYDROCHLORIDE

Official Name

English

ETELCALCETIDE HYDROCHLORIDE [USAN]

Common Name

English

Etelcalcetide hydrochloride [WHO-DD]

Common Name

English

ETELCALCETIDE HYDROCHLORIDE [JAN]

Common Name

English

KAI-4169 HCL

Code

English

TELCALCETIDE HYDROCHLORIDE

Common Name

English

KAI-4169 HYDROCHLORIDE

Code

English

ETELCALCETIDE HYDROCHLORIDE [MI]

Common Name

English

N-ACETYL-D-CYSTEINYL-D-ALANYL-D-ARGINYL-D-ARGINYL-D-ARGINYL-D-ALANYL-D-ARGININAMIDE DISULFIDE WITH L-CYSTEINE HYDROCHLORIDE

Common Name

English

VELCALCETIDE HYDROCHLORIDE

Common Name

English

D-ARGININAMIDE, N-ACETYL-D-CYSTEINYL-D-ALANYL-D-ARGINYL-D-ARGINYL-D-ARGINYL-D-ALANYL-, DISULFIDE WITH L-CYSTEINE, HYDROCHLORIDE

Common Name

English

Code System Code Type Description

DAILYMED

72PT5993DU