Etelcalcetide
(Synonyms: 维拉卡肽,AMG 416; KAI-4169) 目录号 : GC38148
A peptide agonist of CaSR
Cas No.:1262780-97-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Etelcalcetide is a peptide agonist of the calcium-sensing receptor (CaSR).1 It is selective for CaSR over a panel of 33 receptors and ion channels, as well as the norepinephrine transporter at 10 ?M. Etelcalcetide increases intracellular calcium levels in HEK293T cells expressing the human CaSR receptor with an EC50 value of 0.53 ?M. It also inhibits parathyroid secretion from primary rat parathyroid cells (EC50 = 0.36 ?M in the presence of calcium). Etelcalcetide (0.3, 1, and 3 mg/kg) decreases parathyroid hormone and calcium levels in plasma and serum, respectively, in a model of chronic renal insufficiency with secondary hyperthyroidism in nephrectomized rats fed a high-phosphorus diet. Formulations containing etelcalcetide have been used in the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease undergoing hemodialysis.
1.Harada, K., Fujioka, A., Konno, M., et al.Pharmacology of Parsabiv? (etelcalcetide, ONO-5163/AMG 416), a novel allosteric modulator of the calcium-sensing receptor, for secondary hyperparathyroidism in hemodialysis patientsEur. J. Pharmacol.842139-145(2019)
| Cas No. | 1262780-97-1 | SDF | |
| 别名 | 维拉卡肽,AMG 416; KAI-4169 | ||
| 分子式 | C38H73N21O10S2 | 分子量 | 1048.25 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.954 mL | 4.7699 mL | 9.5397 mL |
| 5 mM | 0.1908 mL | 0.954 mL | 1.9079 mL |
| 10 mM | 0.0954 mL | 0.477 mL | 0.954 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients
Am J Kidney Dis 2022 Mar;79(3):362-373.PMID:34273436DOI:10.1053/j.ajkd.2021.05.020.
Rationale & objective: Clinical trial data have demonstrated the efficacy of Etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of Etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017. Study design: New-user design within prospective cohort. Setting & participants: 2,596 new users of Etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). Predictors: Baseline PTH, prior cinacalcet use, initial Etelcalcetide dose. Outcome: Trajectories of Etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after Etelcalcetide initiation. Analytical approach: Cumulative incidence methods for Etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. Results: By August 2019, Etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting Etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after Etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after Etelcalcetide initiation. Limitations: Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. Conclusions: In the 12 months after Etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of Etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.
Etelcalcetide for the treatment of secondary hyperparathyroidism
Expert Opin Pharmacother 2017 Apr;18(5):529-534.PMID:28277829DOI:10.1080/14656566.2017.1303482.
Calcium sensing receptor is an important target for the treatment of secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a novel peptide calcimimetic agent that has a similar mechanism of action as cinacalcet hydrochloride. Clinical trials of Etelcalcetide have been performed in the US, Europe, and Japan, and these trials demonstrated the safety and efficacy of Etelcalcetide in dialysis patients. Etelcalcetide has recently been approved in Europe, the US and Japan. Areas covered: We review the development, pharmacokinetics, and clinical efficacy and safety of Etelcalcetide for the treatment of SHPT in hemodialysis patients. We also summarize the clinical evidence regarding cinacalcet to forecast the potential clinical benefit of Etelcalcetide. Expert opinion: Etelcalcetide is an injectable calcimimetic with a longer elimination half-life than cinacalcet. The injectable formulation improves adherence and reduces pill burden, while the frequency of gastrointestinal adverse events has been comparable between cinacalcet and Etelcalcetide. The longer half-life of Etelcalcetide reduces the fluctuation of biochemical markers of mineral and bone metabolism, but it remains to be determined whether such a sustained effect results in improved outcomes. Further studies are needed to determine the impact of Etelcalcetide on clinical outcomes, particularly in comparison with the conventional calcimimetic cinacalcet.
Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial
Clin J Am Soc Nephrol 2021 Apr 7;16(4):599-612.PMID:33685864DOI:10.2215/CJN.16601020.
Background and objectives: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent Etelcalcetide is more effective in increasing T50 value than a vitamin D receptor activator maxacalcitol. Design, setting, participants, & measurements: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous Etelcalcetide 5 mg thrice weekly (Etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. Results: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (Etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T50 value was changed from 116 minutes (interquartile range, 90-151) to 131 minutes (interquartile range, 102-176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98-174) to 166 minutes (interquartile range, 127-218) in the Etelcalcetide group. The increase in T50 value was significantly greater in the Etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. Conclusions: Etelcalcetide was more effective in increasing T50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. Clinical trial registry name and registration number: VICTORY; UMIN000030636 and jRCTs051180156.
Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis
Circ Res 2021 May 28;128(11):1616-1625.PMID:33825489DOI:10.1161/CIRCRESAHA.120.318556.
[Figure: see text].
Etelcalcetide: First Global Approval
Drugs 2016 Dec;76(18):1787-1792.PMID:27900648DOI:10.1007/s40265-016-0671-3.
Etelcalcetide (Parsabiv™) is a novel second generation calcimimetic agent developed by Amgen for the treatment of secondary hyperparathyroidism (SHPT), a complication of chronic kidney disease (CKD). Etelcalcetide reduces circulating levels of parathyroid hormone and calcium by binding directly to the calcium-sensing receptor. Intravenous Etelcalcetide has been approved in the EU for the treatment of SHPT in adult patients with CKD on haemodialysis therapy. Regulatory applications for Etelcalcetide in SHPT are also under review in the USA and Japan. This article summarizes the milestones in the development of Etelcalcetide leading to this first global approval for the treatment of SHPT.