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Chemistry

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Also known as: Velcalcetide, Parsabiv, 1262780-97-1, Kai-4169, Amg-416, Telcalcetide
Molecular Formula
C38H73N21O10S2
Molecular Weight
1048.3  g/mol
InChI Key
ANIAZGVDEUQPRI-ZJQCGQFWSA-N
FDA UNII
60ME133FJB

Etelcalcetide
Etelcalcetide is a calcimimetic and calcium-sensing receptor (CaSR) agonist composed of a synthetic peptide comprised of seven D-amino acids that can be used to treat secondary hyperparathyroidism (sHPT) in hemodialysis patients with chronic kidney disease (CKD). Upon intravenous administration, etelcalcetide mimics calcium and allosterically binds to and activates the CaSR expressed by the parathyroid gland. This suppresses the synthesis and secretion of parathyroid hormone (PTH), thereby reducing PTH levels and lowering serum calcium and phosphorus levels. Elevated PTH is often observed in patients with CKD and is associated with dysregulated calcium-phosphate homeostasis.
Etelcalcetide is a Calcium-sensing Receptor Agonist. The mechanism of action of etelcalcetide is as an Increased Calcium-sensing Receptor Sensitivity.
1 2D Structure

Etelcalcetide

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(2R)-3-[[(2S)-2-acetamido-3-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-oxopropyl]disulfanyl]-2-aminopropanoic acid
2.1.2 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
2.1.3 InChI Key
ANIAZGVDEUQPRI-ZJQCGQFWSA-N
2.1.4 Canonical SMILES
CC(C(=O)NC(CCCN=C(N)N)C(=O)N)NC(=O)C(CCCN=C(N)N)NC(=O)C(CCCN=C(N)N)NC(=O)C(CCCN=C(N)N)NC(=O)C(C)NC(=O)C(CSSCC(C(=O)O)N)NC(=O)C
2.1.5 Isomeric SMILES
C[C@H](C(=O)N[C@H](CCCN=C(N)N)C(=O)N)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](C)NC(=O)[C@@H](CSSC[C@@H](C(=O)O)N)NC(=O)C
2.2 Other Identifiers
2.2.1 UNII
60ME133FJB
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Amg 416

2. Amg-416

3. Etelcalcetide Hydrochloride

4. Kai-4169

5. Parsabiv

6. Velcalcetide

2.3.2 Depositor-Supplied Synonyms

1. Velcalcetide

2. Parsabiv

3. 1262780-97-1

4. Kai-4169

5. Amg-416

6. Telcalcetide

7. 60me133fjb

8. Ono-5163

9. D-argininamide, N-acetyl-d-cysteinyl-d-alanyl-d-arginyl-d-arginyl-d-arginyl-d-alanyl-, Disulfide With L-cysteine

10. Etelcalcetide [usan:inn]

11. Unii-60me133fjb

12. Kai 4169

13. Amg416

14. Etelcalcetide [mi]

15. Etelcalcetide [inn]

16. Etelcalcetide (usan/inn)

17. Etelcalcetide [usan]

18. Etelcalcetide [who-dd]

19. Gtpl8375

20. Chembl3545184

21. Schembl21982605

22. Dtxsid70155132

23. Chebi:134700

24. Etelcalcetide [orange Book]

25. Hy-p1955

26. Akos037648615

27. Etelcalcetide Hydrochloride(amg-416)

28. Db12865

29. Bs-14875

30. Cs-0030931

31. J3.559.823e

32. D10676

33. D71178

34. Q21098973

35. N-acetyl-d-cysteinyl-d-alanyl-d-arginyl-d-arginyl-d-arginyl-d-alanyl-d-argininamide Disulfide With L-cysteine

36. S-(((s)-2-acetamido-3-(((r)-1-(((r)-1-(((r)-1-(((r)-1-(((r)-1-(((r)-1-amino-5-guanidino-1-oxopentan-2-yl)amino)-1-oxopropan-2-yl)amino)-5-guanidino-1-oxopentan-2-yl)amino)-5-guanidino-1-oxopentan-2-yl)amino)-5-guanidino-1-oxopentan-2-yl)amino)-1-oxopropan-2-yl)amino)-3-oxopropyl)thio)-l-cysteine

2.4 Create Date
2013-06-10
3 Chemical and Physical Properties
Molecular Weight 1048.3 g/mol
Molecular Formula C38H73N21O10S2
XLogP3-10.7
Hydrogen Bond Donor Count18
Hydrogen Bond Acceptor Count17
Rotatable Bond Count36
Exact Mass1047.52906996 g/mol
Monoisotopic Mass1047.52906996 g/mol
Topological Polar Surface Area618 Ų
Heavy Atom Count71
Formal Charge0
Complexity1910
Isotope Atom Count0
Defined Atom Stereocenter Count8
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 1  
Drug NamePARSABIV
Active IngredientETELCALCETIDE
CompanyKAI PHARMS INC (Application Number: N208325. Patents: 8377880, 8999932, 9278995, 9701712, 9820938)

4.2 Drug Indication

Etelcalcetide is a calcium-sensing receptor agonist indicated for: Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.


Parsabiv is indicated for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on haemodialysis therapy.


5 Pharmacology and Biochemistry
5.1 Pharmacology

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.


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
ETELCALCETIDE
5.2.2 FDA UNII
60ME133FJB
5.2.3 Pharmacological Classes
Increased Calcium-sensing Receptor Sensitivity [MoA]; Calcium-sensing Receptor Agonist [EPC]
5.3 ATC Code

H05BX04


H05BX04

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


H - Systemic hormonal preparations, excl. sex hormones and insulins

H05 - Calcium homeostasis

H05B - Anti-parathyroid agents

H05BX - Other anti-parathyroid agents

H05BX04 - Etelcalcetide


5.4 Absorption, Distribution and Excretion

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


Route of Elimination

Etelcalcetide is cleared by renal excretion


Volume of Distribution

796 L


Clearance

7.66 L/hr


5.5 Metabolism/Metabolites

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.


5.6 Biological Half-Life

3 to 4 days


5.7 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.


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[{"dataSource":"API Export","activeIngredients":"","year":"2023","qtr":"Q2","strtotime":1684434600,"product":"ARG7 ACID ETELCALCETIDE","address":"2ND FLOOR, PLOT NO.2, MAITHRIVIHAR, AMEERPET,","city":"HYDERABAD, AP.","supplier":"AURO PEPTIDES LIMITED","supplierCountry":"INDIA","foreign_port":"YELGRAD BEOGRAD","customer":"STADA ARZNEIMITTEL","customerCountry":"GERMANY","quantity":"0.00","actualQuantity":"0.02","unit":"GMS","unitRateFc":"75000","totalValueFC":"1482.7","currency":"USD","unitRateINR":6100000,"date":"19-May-2023","totalValueINR":"122000","totalValueInUsd":"1482.7","indian_port":"HYDERABAD AIR","hs_no":"29371900","bill_no":"0","productDescription":"API","marketType":"REGULATED MARKET","country":"GERMANY","selfForZScoreResived":"Pharma Grade","supplierPort":"HYDERABAD AIR","supplierAddress":"2ND FLOOR, PLOT NO.2, MAITHRIVIHAR, AMEERPET,, HYDERABAD, AP.","customerAddress":""},{"dataSource":"API Export","activeIngredients":"","year":"2023","qtr":"Q4","strtotime":1697481000,"product":"ETELCALCETIDE HYDROCHLORIDE","address":"PLOT NO.C-24, MSN HOUSE, INDUSTRIAL","city":"HYDERABAD, AP","supplier":"MSN LABORATORIES","supplierCountry":"INDIA","foreign_port":"VIENNA","customer":"TO THE ORDER OF","customerCountry":"AUSTRIA","quantity":"0.00","actualQuantity":"0.002","unit":"KGS","unitRateFc":"2400000","totalValueFC":"2967.7","currency":"USD","unitRateINR":123500000,"date":"17-Oct-2023","totalValueINR":"247000","totalValueInUsd":"2967.7","indian_port":"Hyderabad Air","hs_no":"29379020","bill_no":"4701155","productDescription":"API","marketType":"REGULATED MARKET","country":"AUSTRIA","selfForZScoreResived":"Pharma Grade","supplierPort":"Hyderabad Air","supplierAddress":"PLOT NO.C-24, MSN HOUSE, INDUSTRIAL, HYDERABAD, AP","customerAddress":""},{"dataSource":"API Export","activeIngredients":"","year":"2024","qtr":"Q2","strtotime":1718649000,"product":"ETELCALCETIDE (YE)","address":"PLOT NO.C-24, MSN HOUSE, INDUSTRIAL","city":"HYDERABAD, AP","supplier":"MSN LABORATORIES","supplierCountry":"INDIA","foreign_port":"VIENNA","customer":"EVER VALINJECT GMBH","customerCountry":"AUSTRIA","quantity":"0.00","actualQuantity":"0.9","unit":"GMS","unitRateFc":"1500","totalValueFC":"1278.3","currency":"USD","unitRateINR":118572.3,"date":"18-Jun-2024","totalValueINR":"106715.07","totalValueInUsd":"1278.3","indian_port":"Hyderabad Air","hs_no":"29379020","bill_no":"1759287","productDescription":"API","marketType":"REGULATED MARKET","country":"AUSTRIA","selfForZScoreResived":"Pharma Grade","supplierPort":"Hyderabad Air","supplierAddress":"PLOT NO.C-24, MSN HOUSE, INDUSTRIAL, HYDERABAD, AP","customerAddress":""}]
19-May-2023
18-Jun-2024
KGS
overview
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Average Price (USD/KGS)

Number of Transactions

Total Quantity (KGS)

Total Value (USD)

Quantity (KGS) & Unit rate (USD/KGS) over time

API Imports and Exports

Importing Country Total Quantity
(KGS)
Average Price
(USD/KGS)
Number of Transactions

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