Etelcalcetide | CAS 1262780-97-1 / 1334237-71-6 | Calcium-Sensing Receptor Agonist (Research Use Only) | Knowlux
Product Description
Etelcalcetide, CAS 1262780-97-1 (free peptide) / 1334237-71-6 (hydrochloride salt), is a synthetic octapeptide calcimimetic supplied by Knowlux for laboratory research use. The peptide is a D-amino-acid backbone with an L-cysteine linked via disulfide bond to a D-cysteine residue, yielding the structure Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, disulfide with L-cysteine. The molecular formula is C38H73N21O10S2 and the molecular weight is 1048.25 to 1048.26 g/mol on a free-peptide basis. Each lot is released with a lot-specific COA, MSDS and analytical traceability.
CAS, Salt Form, and Naming Clarification: Etelcalcetide circulates under two registries that correspond to different salt forms, and the distinction has practical consequences for solubility, molecular weight, and counter-ion content. CAS 1262780-97-1 is the free peptide registry, associated with formula C38H73N21O10S2 and MW 1048.25 to 1048.26. CAS 1334237-71-6 is the hydrochloride salt registry. The hydrochloride salt is the form used in the marketed drug (Parsabiv) and in many commercial research catalogues; its formula is rendered as C38H73N21O10S2.17/2HCl by MedChemExpress, with a molecular weight of approximately 1353.33 under that stoichiometric assignment, while other suppliers list the hydrochloride with a molecular weight in the 1084 to 1085 range depending on the HCl count and hydration state. Knowlux specifies the salt form, hydrochloride content, and peptide content per lot on the COA. Buyers should confirm whether the quoted material is the free peptide or the hydrochloride salt before procurement, and should reconcile the molecular weight on the COA against the declared counter-ion basis. A naming note is also warranted: Etelcalcetide has been referred to by the development codes AMG 416, KAI-4169, and Velcalcetide; these are the same compound and should not be treated as distinct products.
Structural Note: Etelcalcetide is structurally distinct from every other peptide in this catalogue. It is built on a D-amino-acid backbone, which confers resistance to proteolytic degradation relative to all-L peptides. The N-terminus is acetylated, and the C-terminus is amidated (D-Arg-NH2). The side chain of the N-terminal D-Cys is disulfide-linked to a free L-cysteine, creating a small, solvent-exposed disulfide handle that is essential for CaSR activation. Unlike the large disulfide-constrained macrocycles in the Linaclotide and Ziconotide families, Etelcalcetide is not internally cyclized; the disulfide is intermolecular with respect to the peptide backbone. The peptide is rich in D-arginine (three residues), giving it a strongly cationic character at physiological pH and contributing to its interaction with the extracellular venus flytrap domain of CaSR.
Product Parameters
| Item | Specification |
|---|---|
| Product Name | Etelcalcetide |
| Synonyms | AMG 416; KAI-4169; Velcalcetide; Parsabiv (marketed drug) |
| CAS No. | 1262780-97-1 (free peptide); 1334237-71-6 (hydrochloride salt) |
| Molecular Formula | C38H73N21O10S2 (free peptide); hydrochloride formula varies by HCl stoichiometry |
| Molecular Weight | 1048.25 to 1048.26 g/mol (free peptide); ~1084 to 1353 g/mol reported for hydrochloride forms depending on stoichiometry |
| Sequence (short) | Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, disulfide with L-Cys |
| Sequence Length | 8 residues (heptapeptide backbone plus disulfide-linked cysteine) |
| Key Structural Features | All-D-amino-acid backbone; N-terminal acetyl; C-terminal D-Arg-NH2; intermolecular disulfide with L-Cys; cationic (three D-Arg) |
| Appearance | White to off-white powder or lyophilized powder |
| Solubility | DMSO: 100 mg/mL (92.19 mM) for HCl salt; ~10 mg/mL for free peptide; water: 100 mg/mL (HCl salt) or soluble (free peptide) (see Solubility section) |
| Purity | >=98.0% (HPLC) standard; >=95.0% entry grade |
| Identity | Confirmed by LC-MS and HPLC |
| Grade | Research grade |
| Counter-ion | Free peptide or hydrochloride (lot-specific, declared on COA) |
| Peptide Content | >=80.0% (free peptide reference); >=60.0% minimum in some HCl-salt COAs |
| Acetate Content | <=12.0% (where applicable) |
| Water Content | <=8.0% |
| Single Impurity | <=2.0% (HPLC) |
| Endotoxin | <=50 EU/mg |
| Storage | See Storage and Stability section |
| Packaging | 1 mg / 5 mg / 10 mg / 25 mg / 50 mg / 100 mg vial; bulk on request |
| Application | Laboratory research use only |
| Origin | China |
Product Details
1. Overview
Etelcalcetide is a synthetic peptide calcimimetic that functions as an allosteric activator of the calcium-sensing receptor (CaSR), a class C GPCR expressed on the surface of parathyroid chief cells. Activation of CaSR by Etelcalcetide increases the receptor sensitivity to extracellular calcium, suppressing parathyroid hormone (PTH) secretion and thereby lowering serum PTH, calcium, and phosphorus. Unlike small-molecule calcimimetics such as cinacalcet, Etelcalcetide is a peptide and binds the CaSR extracellular domain in a distinct manner, which is the pharmacological basis for its distinct potency and duration profile. In clinical medicine, Etelcalcetide hydrochloride is approved (FDA, 2017) for secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis. The material supplied under this specification is research-grade and is not intended for human administration.
2. Receptor Pharmacology and Selectivity
Etelcalcetide is a potent and selective CaSR agonist. In HEK293T cells expressing the human CaSR, it increases intracellular calcium with an EC50 of 0.53 microM, and it inhibits PTH secretion from primary rat parathyroid cells with an EC50 of 0.36 microM in the presence of calcium. A separate cell-based assay measuring IP1 accumulation reports an EC50 of 25 microM, which is approximately 50-fold weaker than the calcium-mobilization EC50 and likely reflects differences in assay format, receptor reserve, or the specific signaling endpoint measured. The selectivity of Etelcalcetide for CaSR has been characterized against a panel of 33 receptors and ion channels, with no significant activity at 10 microM except for the norepinephrine transporter; this selectivity profile distinguishes Etelcalcetide from less selective calcimimetics and supports its use as a targeted CaSR tool. In vivo, Etelcalcetide at 0.3, 1, and 3 mg/kg decreases plasma PTH and serum calcium in nephrectomized rats fed a high-phosphorus diet, a model of chronic renal insufficiency with secondary hyperparathyroidism. These values are assay- and system-dependent and are provided for scientific reference only.
3. Research Applications
Published pharmacological characterizations and documented protocols describe the following research applications:
-
CaSR binding and functional activation assays (intracellular calcium mobilization, IP1 accumulation, PTH suppression)
-
Secondary hyperparathyroidism and chronic kidney disease-mineral bone disorder research models
-
Comparative pharmacology of peptide versus small-molecule calcimimetics
-
Selectivity profiling against GPCRs, ion channels, and transporters
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D-amino-acid peptide stability and proteolytic resistance studies
-
Reference standard development for HPLC and LC-MS analytical methods
These descriptions are derived from published research and are provided for scientific reference only.
Quality Control
| Test Item | Method | Acceptance Criteria |
|---|---|---|
| Purity | RP-HPLC | >=95.0% (entry grade); >=98.0% (standard grade); 99% available |
| Identity | LC-MS and HPLC | Consistent with structure (1048.25 to 1048.26 for free peptide) |
| Single Impurity | RP-HPLC | <=2.0% (entry grade); <=1.0% (higher grade) |
| Peptide Content | Nitrogen analysis or AAA | >=80.0% (free peptide reference); >=60.0% minimum in some HCl-salt lots |
| Acetate Content | HPLC | <=12.0% (where applicable) |
| Water Content | Karl Fischer | <=8.0% |
| Endotoxin | LAL or chromogenic | <=50 EU/mg |
| Appearance | Visual | White to off-white powder or lyophilized powder |
Solubility and Handling
Solubility: Etelcalcetide solubility data are reported for both the free peptide and the hydrochloride salt, and the values diverge in a way that reflects counter-ion effects. For the hydrochloride salt, Selleck reports DMSO solubility of 100 mg/mL (92.19 mM) and water solubility of 100 mg/mL (92.19 mM) at 25C, with the caveat that moisture-contaminated DMSO may reduce solubility and fresh anhydrous DMSO should be used; the recommended stock concentration is 10 mM in DMSO. For the free peptide, Cayman and BenchChem report DMSO approximately 10 mg/mL (~8.37 mM) and PBS (pH 7.2) approximately 10 mg/mL. The hydrochloride salt is therefore the more soluble form in both DMSO and water, which is consistent with the counter-ion role in enhancing aqueous and polar-solvent dissolution. For practical stock preparation, the hydrochloride salt is the preferred form where high-concentration stocks are required; the free peptide is viable at lower concentrations in DMSO or PBS. Prepare solutions fresh and aliquot to avoid repeated freeze-thaw cycles.
Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. The disulfide bond between the D-Cys and L-Cys residues is sensitive to reducing agents; avoid contact with dithiothreitol (DTT) or mercaptoethanol during handling. The D-amino-acid backbone confers proteolytic resistance but does not eliminate the need for standard peptide hygiene practices.
Storage and Stability
| Format | Temperature | Shelf Life |
|---|---|---|
| Lyophilized Powder | -20C, sealed, desiccated, protected from light | 3 years (InvivoChem, Cayman, CymitQuimica); >=2 years (MyBioSource) |
| Lyophilized Powder | 4C, sealed, desiccated | 2 years (InvivoChem) |
| Reconstituted Solution | -80C, aliquoted, sealed | 6 months (InvivoChem, GlpBio); 1 year (select suppliers) |
| Reconstituted Solution | -20C, aliquoted, sealed | 1 month (InvivoChem, GlpBio, BenchChem) |
Documentation Support
Per lot: COA, MSDS, HPLC chromatogram, and mass spectrometry data. Salt-form identity, hydrochloride content, peptide content, and water content available on request. Custom specifications and third-party inspection can be arranged on a project basis.
About Knowlux
Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.
Compliance Statement
FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.
This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. Etelcalcetide hydrochloride is an approved medicinal product (Parsabiv) in certain jurisdictions for secondary hyperparathyroidism in hemodialysis patients; however, the material offered under this specification is research-grade and is not intended for clinical use. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.
Data Verification Notes
The free-peptide formula C38H73N21O10S2 and MW 1048.25 to 1048.26 are confirmed by KEGG DRUG, ChemicalBook, MedChemExpress, InvivoChem, GlpBio, BOC Sciences, and MyBioSource. The sequence Ac-D-Cys-D-Ala-D-Arg-D-Arg-D-Arg-D-Ala-D-Arg-NH2, disulfide with L-cysteine, is confirmed by ChemicalBook, MedChemExpress, and the patent literature. The all-D-amino-acid backbone and the intermolecular disulfide with L-cysteine are confirmed by the ScienceDirect nonclinical pharmacology paper. The CaSR EC50 of 0.53 microM (HEK293T, intracellular calcium) and 0.36 microM (primary rat parathyroid cells, PTH inhibition) are from GlpBio and Bertin Bioreagent; the IP1 EC50 of 25 microM is from ProbeChem and Bioquote. The 33-receptor/ion-channel selectivity panel and the norepinephrine transporter activity at 10 microM are from GlpBio and 10xChem. The in vivo PTH and calcium data (0.3, 1, 3 mg/kg, nephrectomized rat model) are from GlpBio. The hydrochloride salt CAS 1334237-71-6 is confirmed by InvivoChem, MedChemExpress, Cayman, and the Japanese JAN database. The hydrochloride formula C38H73N21O10S2.17/2HCl and MW 1353.33 are from MedChemExpress; alternative hydrochloride molecular weights in the 1084 to 1085 range are from CymitQuimica and other suppliers and reflect differences in HCl stoichiometry or hydration. Solubility values are reported with their source conditions rather than reconciled into a single figure because the DMSO and water data differ by an order of magnitude between the hydrochloride salt and the free peptide. Storage shelf-life divergence (3 years versus >=2 years at -20C for powder; 6 months versus 1 year at -80C for solutions) is reported as-is; the -20C powder condition is the most widely supported archival temperature.
Formatting Note: All formulas, sequences, and comparison operators use plain ASCII notation to prevent character corruption on the platform. Section headings, table alignment, and spacing follow the approved product detail pattern. No trailing spaces or non-breaking characters are used; tables use consistent pipe alignment.
