ArticlePloS one2018
A novel calcimimetic agent, evocalcet (MT-4580/KHK7580), suppresses the parathyroid cell function with little effect on the gastrointestinal tract or CYP isozymes in vivo and in vitro.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- First-in-Patient Phase I/II Study of Upacicalcet in Japanese Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: Pharmacokinetic and Pharmacodynamic Properties.Clinical pharmacokinetics · 2022Trial
- Predictive factors requiring high-dose evocalcet in hemodialysis patients with secondary hyperparathyroidism.PloS one · 2022Trial
- Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week, dose-titration phase III study.Journal of bone and mineral metabolism · 2020Trial
- Efficacy and safety of evocalcet in Japanese peritoneal dialysis patients.Clinical and experimental nephrology · 2019Trial
- Long-Term Efficacy and Safety of Evocalcet in Japanese Patients with Secondary Hyperparathyroidism Receiving Hemodialysis.Scientific reports · 2019Trial
- Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients.Clinical and experimental nephrology · 2019Trial
- Trial
- Upacicalcet: A Novel Intravenous Calcimimetic Agent for Patients Undergoing Hemodialysis With Secondary Hyperparathyroidism.Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy · 2026Review
- Evocalcet improved the PTH-calcium setpoint and suppressed parathyroid proliferation in mice model of primary hyperparathyroidism.Journal of bone and mineral metabolism · 2026Article
- Effectiveness of evocalcet for hypercalcemia in patients with primary hyperparathyroidism.Endocrine journal · 2025Article
- Bone in Parathyroid Diseases Revisited: Evidence From Epidemiological, Surgical and New Drug Outcomes.Endocrine reviews · 2025Review
- Bioanalytical tandem mass spectrometry method for cinacalcet in human plasma: green assessment with advanced metrics.Bioanalysis · 2025Article
- Calcimimetics and Vascular Calcification.Toxins · 2025Review
- The calcium-sensing receptor: a comprehensive review on its role in calcium homeostasis and therapeutic implications.American journal of translational research · 2025Review
- Successful Treatment With Evocalcet Against Familial Hypocalciuric Hypercalcemia Type 3 (FHH3) Identified byCase reports in endocrinology · 2025Article
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
- Pharmacokinetics, Pharmacodynamics, and Safety of Evocalcet (KHK7580), a Novel Calcimimetic Agent: An Open-Label, Single- and Multiple-Dose, Phase I Trial in Healthy Chinese Subjects.Drug design, development and therapy · 2024Article
- Article
- Efficacy of Evocalcet in Previously Cinacalcet-Treated Secondary Hyperparathyroidism Patients.Kidney international reports · 2021Article
- Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor.ACS pharmacology & translational science · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cinacalcet hydrochloride (cinacalcet), an oral calcimimetic agent has been widely used for the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In sharp contrast to vitamin D receptor activators, cinacalcet suppresses SHPT without inducing hypercalcemia or hyperphosphatemia. Nevertheless, some patients remain refractory to SHPT with this agent, as the dose cannot be sufficiently increased due to gastrointestinal symptoms. In order to resolve this issue, we have developed a newly synthesized calcimimetic agent, evocalcet (MT-4580/KHK7580). In a rat model of CKD induced by 5/6 nephrectomy, oral administration of evocalcet efficiently suppressed the secretion of parathyroid hormone (PTH). With regard to the gastro-intestinal effects, cinacalcet induced a significant delay in gastric emptying in rats, while evocalcet did no marked effects on it. Evocalcet also demonstrated the less induction of emesis compared to cinacalcet in common marmosets. The pharmacological effects of evocalcet were observed at lower doses because of its higher bioavailability than cinacalcet, which may have contributed to the reduced GI tract symptoms. In addition, evocalcet showed no substantial direct inhibition of any CYP isozymes in in vitro liver microsome assay, suggesting a better profile in drug interactions than cinacalcet that inhibits cytochrome P450 (CYP) 2D6. These findings suggest that evocalcet can be a better alternative to cinacalcet, an oral calcimimetic agent, with a wider safety margin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.