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Seven D-amino acids with a disulfide-tethered cysteine: an intravenous calcimimetic given at the end of dialysis, so nobody has to remember a daily pill.
Also known as: AMG 416 · AMG-416 · KAI-4169 · velcalcetide · Parsabiv
Part of the Foundational & therapeutic peptides cluster
Overview
Etelcalcetide (Parsabiv, AMG 416) is a synthetic seven-residue D-amino-acid peptide with a disulfide-linked L-cysteine that activates the calcium-sensing receptor and lowers parathyroid hormone. Given intravenously three times a week at the end of haemodialysis, it was approved by the EMA in 2016 and the FDA in February 2017 for secondary hyperparathyroidism in chronic kidney disease; in a head-to-head trial it beat oral cinacalcet, with 68.2% versus 57.7% of patients achieving a >30% PTH reduction.
Source & context
Biological / chemical source: Synthetic D-amino-acid peptide (Amgen)
Primary research or clinical context: Approved (EMA, 2016; US FDA, February 2017) for secondary hyperparathyroidism in adults with chronic kidney disease on haemodialysis
What etelcalcetide is
Etelcalcetide is a second-generation calcimimetic: a drug that mimics calcium at the calcium-sensing receptor on parathyroid cells, tricking the gland into secreting less parathyroid hormone (PTH). It was developed by Amgen (as AMG 416, earlier KAI-4169) for secondary hyperparathyroidism, the overproduction of PTH that complicates chronic kidney disease and drives bone and vascular disease in dialysis patients. Intravenous etelcalcetide was approved by the EMA in 2016 and by the US FDA in February 2017 for adults with chronic kidney disease on haemodialysis, and it has also been approved in Japan (Blair, Drugs 2016; Hamano et al., Expert Opinion on Pharmacotherapy 2017).
Sequence and chemistry
Etelcalcetide's seven-residue backbone — cysteine, alanine, three arginines, alanine, arginine — is built entirely from D-amino acids, which makes it invisible to the proteases that would destroy an L-peptide within minutes in blood. The N-terminal D-cysteine is acetylated and linked by a disulfide bond to a separate L-cysteine, and the C-terminal arginine is amidated (IUPHAR record). The one-letter display above shows CARRRAR; the structure block gives the molecular formula C38H73N21O10S2 and mass of about 1,048 Da from PubChem. That disulfide is functionally important — it can exchange with cysteine residues on the receptor.
Mechanism: a different way to activate the same receptor
The calcium-sensing receptor detects extracellular calcium and suppresses PTH release when levels are adequate. Cinacalcet, the first calcimimetic, is an oral allosteric modulator that makes the receptor more sensitive to calcium. Etelcalcetide binds directly and acts as a peptidic agonist through a mechanism IUPHAR describes as distinct from cinacalcet's allosteric modulation. Both lower PTH and calcium (Eidman & Wetmore, Seminars in Dialysis 2018). The practical difference is delivery: etelcalcetide is injected into the dialysis line three times a week at the end of each session, removing the adherence problem of a daily oral drug.
Head-to-head with cinacalcet
A randomised, double-blind, double-dummy trial at 164 sites in the US, Canada, Europe, Russia and New Zealand enrolled 683 haemodialysis patients with PTH above 500 pg/mL on active therapy, comparing intravenous etelcalcetide (three times weekly) with oral cinacalcet (daily) over 26 weeks. Etelcalcetide was non-inferior and then superior: 68.2% of etelcalcetide patients versus 57.7% of cinacalcet patients achieved a PTH reduction of more than 30% (difference −10.5%, 95% CI −17.5% to −3.5%; P for superiority 0.004), and 52.4% versus 40.2% achieved a reduction of more than 50%. The most common adverse effect was decreased blood calcium, in 68.9% versus 59.8% (Block et al., JAMA 2017).
| Endpoint | Etelcalcetide (n = 340) | Cinacalcet (n = 343) |
|---|---|---|
| PTH reduction > 30% | 68.2% | 57.7% |
| PTH reduction > 50% | 52.4% | 40.2% |
| Decreased blood calcium (adverse effect) | 68.9% | 59.8% |
Effects on bone
Secondary hyperparathyroidism is associated with osteoporosis and fractures, and until recently the skeletal effects of etelcalcetide were unknown. A single-arm, open-label 36-week prospective trial in adults on haemodialysis for at least a year, without recent calcimimetic exposure, measured areal bone mineral density by DXA, trabecular bone score, and peripheral volumetric density, geometry, microarchitecture and estimated strength by high-resolution peripheral quantitative CT before and after treatment, testing the hypothesis that etelcalcetide improves bone quality and strength without damaging tissue quality (Khairallah et al., Clinical Journal of the American Society of Nephrology 2023).
Status and ongoing trials as of September 2026
Etelcalcetide is an approved prescription medicine in the EU, US and Japan. ClinicalTrials.gov lists 23 studies, including two recruiting phase 3 paediatric trials in children with secondary hyperparathyroidism on dialysis, a completed phase 2 study of its effect on chronic kidney disease–mineral and bone disorder, and a study on preserving vitamin-K-dependent protein activity. Hypocalcaemia is the expected, mechanism-based side effect and is the reason its use is limited to monitored dialysis patients (Baker, Hospital Pharmacy 2017). Nothing here is guidance on its use.
Relation to other peptides on this site
Etelcalcetide is the directory's only calcimimetic and one of its few all-D-amino-acid drugs — the same protease-evasion strategy seen in some antimicrobial and opioid peptides profiled here. Parathyroid hormone, the hormone it suppresses, and the PTH analogues teriparatide and abaloparatide, which are given to build bone by the opposite logic, are its natural comparators.
Sequence
One-letter sequence commonly cited for Etelcalcetide (educational; isoforms and modifications may differ):
CARRRAR
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, with the D-cysteine joined by a disulfide to an L-cysteine
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C38H73N21O10S2
- Average reference mass
- ≈ 1,048.3
- Receptors
- Calcium-sensing receptor (CaSR), a class C G-protein-coupled receptor; direct peptidic agonist, distinct from the allosteric modulator cinacalcet
- Backbone
- Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, with the D-cysteine joined by a disulfide to an L-cysteine
- Status
- Approved: EMA, 2016; US FDA, February 2017 (secondary hyperparathyroidism in adults with CKD on haemodialysis); also approved in Japan
N-terminal D-cysteine is joined by a disulphide bond to a hydroxylated L-cysteine residue; the D-cysteine is acetylated and the C-terminal arginine is amidated (IUPHAR record).
- PubChem CID: 71511839
- IUPHAR ligand: 8375
- ChEMBL: CHEMBL3545184
- DrugBank: DB12865
- CAS RN: 1262780-97-1
- UNII: 60ME133FJB
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 23 registered studies with “Etelcalcetide” as an intervention (snapshot 2026-09-07). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT03969329 | A Phase 3 Study of Etelcalcetide in Children With Secondary Hyperparathyroidism Receiving Hemodialysis | Phase 3 | recruiting | 2026-08-21 |
| NCT06690242 | MT1013 Injection for the Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease | Phase 2 | completed | 2026-07-22 |
| NCT03633708 | A Trial of Etelcalcetide in Pediatric Participants With Secondary Hyperparathyroidism and Chronic Kidney Disea | Phase 3 | recruiting | 2026-02-27 |
| NCT06352957 | Use of ETElcalcetidefor pReserving vitamiN K-dependent proteIn activiTY ITAlian Study | — | not yet recruiting | 2024-04-08 |
| NCT03960437 | The Effect of Etelcalcetide on CKD-MBD | Phase 2 | completed | 2023-09-21 |
| NCT03795558 | A Study to Investigate the Influence of PTH-lowering by Etelcalcetide (Parsabiv®) on the Calcification Propens | Phase 2 | completed | 2022-03-23 |
Etelcalcetide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, with the D-cysteine joined by a disulfide to an L-cysteineAverage reference mass: 1,048.3 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 8375 and PubChem CID 71511839.
- TrialsClinicalTrials.gov snapshot added: 23 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Etelcalcetide
What is Etelcalcetide?+
Etelcalcetide (Parsabiv, AMG 416) is a synthetic seven-residue D-amino-acid peptide with a disulfide-linked L-cysteine that activates the calcium-sensing receptor and lowers parathyroid hormone. Given intravenously three times a week at the end of haemodialysis, it was approved by the EMA in 2016 and the FDA in February 2017 for secondary hyperparathyroidism in chronic kidney disease; in a head-to-head trial it beat oral cinacalcet, with 68.2% versus 57.7% of patients achieving a >30% PTH reduction.
What Canadian product status is recorded for Etelcalcetide?+
Canadian product status for Etelcalcetide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Etelcalcetide?+
Etelcalcetide is commonly described as approximately 7 amino acids (Peptide calcimimetic).
What is etelcalcetide?+
A synthetic seven-residue D-amino-acid peptide calcimimetic (Parsabiv, AMG 416) that activates the calcium-sensing receptor and lowers parathyroid hormone. Approved in the EU (2016), US (2017) and Japan for secondary hyperparathyroidism on haemodialysis.
How is etelcalcetide different from cinacalcet?+
Cinacalcet is an oral allosteric modulator taken daily; etelcalcetide is a direct peptide agonist injected three times a week at the end of dialysis. In a head-to-head trial, 68.2% versus 57.7% achieved a >30% PTH reduction.
What is the main side effect of etelcalcetide?+
Low blood calcium, reported in 68.9% of patients versus 59.8% on cinacalcet in the comparison trial — an expected consequence of the mechanism.
Why is etelcalcetide made of D-amino acids?+
D-amino acids resist proteolytic degradation, giving the peptide a duration of action compatible with three-times-weekly intravenous dosing.
What is the sequence of etelcalcetide?+
Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, with the D-cysteine disulfide-bonded to an L-cysteine — CARRRAR in one-letter code.
Related peptides
References & further reading
- 1.Block GA et al. (2017). Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA
- 2.Blair HA (2016). Etelcalcetide: First Global Approval. Drugs
- 3.Hamano N et al. (2017). Etelcalcetide for the treatment of secondary hyperparathyroidism. Expert Opinion on Pharmacotherapy
- 4.Eidman KE & Wetmore JB (2018). Treatment of secondary hyperparathyroidism: How do cinacalcet and etelcalcetide differ? Seminars in Dialysis
- 5.Khairallah P et al. (2023). Changes in Bone Quality after Treatment with Etelcalcetide. Clinical Journal of the American Society of Nephrology
- 6.Baker DE (2017). Formulary Drug Review: Etelcalcetide. Hospital Pharmacy
- 7.PubChem — Etelcalcetide (CID 71511839)