CASR calcium sensing receptor
ENSG00000036828 · protein coding · Open Targets profile
G protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (PubMed:17555508, PubMed:19789209, PubMed:21566075, PubMed:22114145, PubMed:22789683, PubMed:23966241, PubMed:25104082, PubMed:25292184, PubMed:25766501, PubMed:26386835, PubMed:32817431, PubMed:33603117, PubMed:34194040, PubMed:34467854, PubMed:7759551, PubMed:8636323, PubMed:8702647, PubMed:8878438). Senses fluctuations in the circulating calcium concentration: activated by elevated circulating calcium, leading to decreased parathyroid hormone (PTH) secretion in parathyroid glands (By similarity). In kidneys, acts as a key regulator of renal tubular calcium resorption (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:38632411). CASR is coupled with different G(q)/G(11), G(i)/G(o)- or G(s)-classes of G proteins depending on the context (PubMed:38632411). In the parathyroid and kidney, CASR signals through G(q)/G(11) and G(i)/G(o) G proteins: G(q)/G(11) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, while G(i)/G(o) coupling mediates inhibition of adenylate cyclase activity (PubMed:38632411, PubMed:7759551). The G protein- coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation (PubMed:27386547, PubMed:27434672, PubMed:32817431, PubMed:33603117, PubMed:34194040). Acts as an activator of the NLRP3 inflammasome via G(i)/G(o)-mediated signaling: down-regulation of cyclic AMP (cAMP) relieving NLRP3 inhibition by cAMP (PubMed:32843625). Acts as a regulator of proton-sensing receptor GPR68 in a seesaw manner: CASR-mediated signaling inhibits GPR68 signaling in response to extracellular calcium, while GPR68 inhibits CASR in presence of extracellular protons (By similarity). {ECO:0000250|UniProtKB:P48442, ECO:0000250|UniProtKB:Q9QY96, ECO:0000269|PubMed:17555508, ECO:0000269|PubMed:19789209, ECO:0000269|PubMed:21566075, ECO:0000269|PubMed:22114145, ECO:0000269|PubMed:22789683, ECO:0000269|PubMed:23966241, ECO:0000269|PubMed:25104082, ECO:0000269|PubMed:25292184, ECO:0000269|PubMed:25766501, ECO:0000269|PubMed:26386835, ECO:0000269|PubMed:27386547, ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:32817431, ECO:0000269|PubMed:32843625, ECO:0000269|PubMed:33603117, ECO:0000269|PubMed:34194040, ECO:0000269|PubMed:34467854, ECO:0000269|PubMed:38632411, ECO:0000269|PubMed:7759551, ECO:0000269|PubMed:8636323, ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8878438}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.3327600061893463 (upper bound 0.47143998742103577). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 15 registry trials, updated in the last three years, of the most advanced drugs against CASR (etelcalcetide, evocalcet, cinacalcet, ASP7991, ronacaleret), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Aihua ZhangPeking University Third Hospital · 1 of 1 trials Phase 2+
- Aili JiangTianjin Medical University Second Hospital · 1 of 1 trials Phase 2+
- Anne F CailleuxUniversity Hospital of Rouen, France: · 1 of 1 trials Phase 2+
- Chaosheng ChenFirst Affiliated Hospital of Wenzhou Medical University · 1 of 1 trials Phase 2+
- Dolores M. ShobackSan Francisco VA Medical Center, San Francisco, CA · 1 of 1 trials Phase 2+
- Guanqing XiaoFirst People's Hospital of Foshan · 1 of 1 trials Phase 2+
- Guohua DingHubei General Hospital · 1 of 1 trials Phase 2+
- Hong LiuSecond Xiangya Hospital of Central South University · 1 of 1 trials Phase 2+
- Jean Marc J KuhnUniversity Hospital of Rouen, France: · 1 of 1 trials Phase 2+
- Jianming YeThe First People's Hospital of Kunshan · 1 of 1 trials Phase 2+
- Jianying NiuFudan University · 1 of 1 trials Phase 2+
- Jiazhuang LouThe First Affiliated Hospital with Nanjing Medical University · 1 of 1 trials Phase 2+
- Jing ChenHuashan Hospital · 1 of 1 trials Phase 2+
- Junwei YangSecond Affiliated Hospital of Nanjing Medical University · 1 of 1 trials Phase 2+
- Li HaoThe Second Hospital of Anhui Medial University · 1 of 1 trials Phase 2+
Registry trials of etelcalcetide, evocalcet, cinacalcet, ASP7991, ronacaleret updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 13 of 15 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
11 trials of drugs against CASR were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of etelcalcetide, evocalcet, cinacalcet, ASP7991, ronacaleret, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 11 most recent of 11.
- terminated · 2025-04-29 · Montefiore Medical Center · Cinacalcet HCl“Based on information in IRB archives the study was terminated in 2009 due to low enrollment”
- terminated · 2021-04-23 · Montefiore Medical Center · Cinacalcet“Study was not renewed with the IRB”
- withdrawn · 2020-12-17 · Children's Mercy Hospital Kansas City · CinacalcetNo reason given
- terminated · 2020-06-29 · Amgen · Cinacalcet HCl“Amgen decided to terminate the study early to be able to meet US regulatory timelines fo filing. Subjects in treatment were rolled over to the 20140159 study.”
- terminated · 2020-06-29 · Amgen · cinacalcet capsule“Study was put on clinical hold on 30 Jan 2013 following a subject fatality. Study was never restarted and was closed.”
- terminated · 2020-06-17 · Amgen · Cinacalcet hydrochloride“Amgen decided to terminate the study early to be able to meet US regulatory timelines fo filing. Subjects in treatment were rolled over to the 20140159 study.”
- terminated · 2018-07-05 · National Institute of Dental and Craniofacial Research (NIDCR) · matched by the registry's drug synonymsNo reason given
- terminated · 2017-11-07 · GlaxoSmithKline · Ronacaleret“Terminated for futility by sponsor after a pre-planned interim review of data”
- terminated · 2017-04-13 · KAI Pharmaceuticals · Etelcalcetide“Study was terminated early to allow subjects to roll over to study NCT02102204.”
- terminated · 2016-05-16 · Centre Hospitalier Universitaire, Amiens · cinacalcet“Financial problem”
- terminated · 2014-10-29 · Papageorgiou General Hospital · cinacalcet“due to financial problems”
Paediatric incentives and obligations for CASR's drugs
For etelcalcetide, evocalcet, cinacalcet, ASP7991, ronacaleret: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · CASR is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001554-PIP01-13-M03 (Etelcalcetide, Treatment of hyperparathyroidism): PM: decision on the application for modification of an agreed PIP, 13 Apr 2022; EMEA-000078-PIP01-07-M08 (cinacalcet hydrochloride, Treatment of parathyroid carcinoma;Treatment of primary hyperparathyroidism;Treatment of secondary hyperparathyroidism in patients with end-stage renal disease): PM: decision on the application for modification of an agreed PIP, 12 May 2017; compliance positive 19 May 2017Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names etelcalcetide, evocalcet, cinacalcet, asp7991, ronacaleretRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Cinacalcet Accordpharma: authorised since 3 Apr 2020; Parsabiv: authorised since 11 Nov 2016; Mimpara: withdrawn since 22 Oct 2004; Cinacalcet Viatris (previously Cinacalcet Mylan): authorised since 19 Nov 2015; +1 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of etelcalcetide, evocalcet, cinacalcet, asp7991, ronacaleretRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 13 interventional studies of etelcalcetide, evocalcet, cinacalcet, asp7991, ronacaleret include patients under 18; 2 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 7 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.