CALCRL calcitonin receptor like receptor
ENSG00000064989 · protein coding · Open Targets profile
G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs) (PubMed:32296767, PubMed:33602864, PubMed:8626685). Together with RAMP1, form the receptor complex for calcitonin-gene-related peptides CALCA/CGRP1 and CALCB/CGRP2 (PubMed:33602864). Together with RAMP2 or RAMP3, function as receptor complexes for adrenomedullin (ADM and ADM2) (PubMed:32296767, PubMed:9620797). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Activates cAMP-dependent pathway (PubMed:32296767, PubMed:8626685). {ECO:0000269|PubMed:32296767, ECO:0000269|PubMed:33602864, ECO:0000269|PubMed:8626685, ECO:0000269|PubMed:9620797}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.4470899999141693 (upper bound 0.6165500283241272). 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 109 registry trials, updated in the last three years, of the most advanced drugs against CALCRL (rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, BI-44370, olcegepant, MK3207), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Todd J SchwedtMayo Clinic · 2 of 2 trials Phase 2+
- Todd SchwedtMayo Clinic · 2 of 2 trials Phase 2+
- Bradley TorphyChicago Headache Center & Research Institute · 1 of 1 trials Phase 2+
- Carolyn A BernsteinBrigham and Women's · 1 of 1 trials Phase 2+
- Carrie RobertsonMayo Clinic · 1 of 1 trials Phase 2+
- Charles ArgoffAlbany Medical College · 1 of 1 trials Phase 2+
- David L BrodyUniformed Services University of the Health Sciences · 1 of 1 trials Phase 2+
- Domenick T ZeroIndiana University · 1 of 1 trials Phase 2+
- Harold C AvilaIndiana University · 1 of 1 trials Phase 2+
- Jeffrey D SharonUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Jessica AilaniMedStar's Georgetown University Hospital · 1 of 1 trials Phase 2+
- Jonathan SchimmelIcahn School of Medicine at Mount Sinai · 1 of 1 trials Phase 2+
- Konrad P WeberUniversity Hospital Zurich, Department of Neurology · 1 of 1 trials Phase 2+
- Kristen K. SteenersonStanford University · 1 of 1 trials Phase 2+
- Kurt KroenkeRegenstrief Institute, Inc. · 1 of 1 trials Phase 2+
Registry trials of rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, BI-44370, olcegepant, MK3207 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; 74 of 103 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. 6 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
20 trials of drugs against CALCRL were stopped early
Terminated, withdrawn and suspended interventional trials of rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, BI-44370, olcegepant, MK3207, 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 20 most recent of 20.
- terminated · 2026-04-29 · Icahn School of Medicine at Mount Sinai · Rimegepant, Zavegepant“Study closing at current site. Study to start as new at different site.”
- terminated · 2026-02-27 · Beth Israel Deaconess Medical Center · matched by the registry's drug synonyms“poor enrollment”
- withdrawn · 2026-01-13 · Pfizer · Zavegepant 10 mg“Strategic decision to cancel the study based on adjusted clinical development plan.”
- terminated · 2025-09-29 · Danish Headache Center · Rimegepant 75 MG“Issues with recruitment”
- withdrawn · 2025-08-14 · United States Naval Medical Center, Portsmouth · Erenumab“Lapse in IRB approval”
- terminated · 2025-05-31 · Messoud Ashina, MD · Ubrogepant 50Mg Tab“Issues with recruitment”
- terminated · 2025-03-27 · Pfizer · BHV-3500 (zavegepant)“Strategic decision to discontinue the study based on adjusted clinical development plan. This decision is not based on any safety concerns.”
- terminated · 2024-07-19 · Pfizer · Zavegepant“Strategic decision to discontinue the study based on adjusted clinical development plan. This decision is not based on any safety concerns.”
- terminated · 2024-06-10 · Pfizer · Rimegepant“Strategic decision to discontinue the study based on adjusted clinical development plan. This decision is not based on any safety concerns.”
- terminated · 2024-05-29 · H. Lundbeck A/S · Erenumab“The study was terminated due to enrolment challenges.”
- terminated · 2024-05-16 · Pfizer · Rimegepant“Strategic decision to discontinue the study based on adjusted clinical development plan. This decision is not based on any safety concerns.”
- terminated · 2024-05-02 · Pfizer · Zavegepant (BHV-3500)“Lack of enrollment due to evolution of COVID-19 pandemic with reduction in patients at risk for severe disease and growing number of effective alternative therapies”
- terminated · 2024-04-02 · University of Maryland, Baltimore · Erenumab-Aooe 70 MG in 1 mL Prefilled Syringe“Low enrollment rate”
- terminated · 2024-03-22 · University of Maryland, Baltimore · Erenumab-Aooe“Low enrollment rate”
- terminated · 2023-02-17 · Mayo Clinic · Erenumab“difficulty with recruitment”
- terminated · 2022-07-20 · Amgen · Erenumab“Terminated [Study would not complete enrollment target until 2026 with results available in 2027. The information will not be useful at that time.]”
- withdrawn · 2022-02-28 · Mayo Clinic · matched by the registry's drug synonyms“Lack of funding to support the trial.”
- withdrawn · 2022-02-22 · Mayo Clinic · Erenumab“No Participants Enrolled”
- withdrawn · 2020-06-01 · Novartis Pharmaceuticals · erenumab 70mg/mL“No patients were enrolled and global prioritization of pipeline and research strategy”
- terminated · 2018-10-18 · Merck Sharp & Dohme LLC · Telcagepant 140 mg, Telcagepant 280 mg, 140 mg telcagepant placebo, 280 mg telcagepant placebo“The study was terminated based on a recommendation of the DSMB following the identification of two patients with significant elevations in serum transaminases”
Paediatric incentives and obligations for CALCRL's drugs
For rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, BI-44370, olcegepant, MK3207: 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 · CALCRL 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 · EMA/PE/0000242151 (erenumab, Prevention of migraine headaches): PM: decision on the application for modification of an agreed PIP, 12 Jun 2025; EMA/PE/0000225746 (atogepant, Prevention of migraine headaches): PM: decision on the application for modification of an agreed PIP, 2 Jan 2025; EMEA-002812-PIP02-20-M03 (rimegepant, Treatment of migraine headaches): PM: decision on the application for modification of an agreed PIP, 13 Sept 2024; EMEA-002812-PIP01-20 (rimegepant, Prevention of migraine headaches): W: decision granting a waiver in all age groups for all conditions or indications, 12 Aug 2020; +1 moreRule: 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 rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, bi-44370, olcegepant, mk3207Rule: 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 · Vydura: authorised since 25 Apr 2022; Aimovig: authorised since 26 Jul 2018; Aquipta: authorised since 11 Aug 2023Rule: 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 rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, bi-44370, olcegepant, mk3207Rule: 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 · 12 interventional studies of rimegepant, zavegepant, erenumab, atogepant, ubrogepant, telcagepant, davalintide, bi-44370, olcegepant, mk3207 include patients under 18; 11 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 12 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.