ETELCALCETIDE

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

Structure Search

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

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 2678		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 8429	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 (total weekly dose) 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 Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	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 Page: p. 30

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 Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30	unhealthy n = 503 Health Status: unhealthy Population Size: 503 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf Page: p. 30

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 OAT1 599 OAT3 642 OCT2 647 OATP1B1 788 OATP1B2 6 PEPT1 20 PEPT2 10 BSEP 402 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882	P-gp 1537 BCRP 561 OAT1 326 OAT3 339 OCT2 355 OATP1B1 406 OATP1B2 7 PEPT1 49 PEPT2 32 BSEP 52 P450 3	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 55, (ClinPharm) 7, 26	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 54-55, (ClinPharm) 7, 26	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, (ClinPharm) 7, 26	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 54-55, (ClinPharm) 7, 26	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, (ClinPharm) 7, 26	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, (ClinPharm) 7, 26	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=66 Page: 54-55, (ClinPharm) 7, 26	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=65 Page: 54, 55, (ClinPharm) 7, 26	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B2 6	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
PEPT1 22	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
PEPT2 12	inhibitor 3277 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 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000ClinPharmR.pdf#page=8 Page: 7, 26	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OATP1B2 7	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
P450 3	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=57 Page: 46-48, 52-53, (ClinPharm) 7, 26	no
PEPT1 49	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000PharmR.pdf#page=56 Page: 45, (ClinPharm) 7, 26	no
PEPT2 32	substrate 3367 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 1647	inhibitor 1626 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
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-267793	https://www.thebiotek.com/product/inhibitors/bt-267793
THE BioTek	bt-242394	https://www.thebiotek.com/product/peptides/bt-242394
eNovation Chemicals	D674080	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674080

PubMed

Title	Date	PubMed
Formulary Drug Review: Etelcalcetide.	2017 Nov	29276237

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

ETELCALCETIDE

Official Name

English

ETELCALCETIDE [MI]

Common Name

English

TELCALCETIDE

Common Name

English

Etelcalcetide [WHO-DD]

Common Name

English

ONO-5163

Code

English

VELCALCETIDE

Common Name

English

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

Common Name

English

etelcalcetide [INN]

Common Name

English

KAI-4169

Code

English

PARSABIV

Brand Name

English

ETELCALCETIDE [USAN]

Common Name

English

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

Common Name

English

AMG-416

Code

English

ETELCALCETIDE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

WHO-ATC

H05BX04