Protein / target

Calcitonin gene-related peptide type 1 receptor

Encoded byCALCRLQ16602Homo sapiensSwiss-Prot

UniProt: Q16602 Ensembl: ENSG00000064989 HGNC: HGNC:16709 NCBI Gene: 10203

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Calcitonin gene-related peptide receptor

Strongest disease association

Hypertension

Via encoding gene CALCRL · Genetic evidence · score 0.72

Therapeutic position

Established drug target

Small molecules and antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs).

View complete UniProt function annotation

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)

Subcellular location

Cell membrane

Domains and Gene Ontology detail (22)

Gene Ontology

Cadrenomedullin receptor complex
CCGRP receptor complex
Ccytoplasm
Cendoplasmic reticulum
Cendosome
Clysosome
Cplasma membrane
Fadrenomedullin binding
Fadrenomedullin receptor activity
Fcalcitonin gene-related peptide receptor activity
Fcalcitonin receptor activity
FG protein-coupled receptor activity

461 aa · 53 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingUniProt · GO

View supporting evidence

G protein-coupled signalling

·G protein-coupled receptor which specificity is determined by its interaction with recep…
·G protein-coupled receptor activity
·adenylate cyclase-activating G protein-coupled receptor signaling pathway
·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

2 medicines · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Migraine Disorders2 medicines

atogepant erenumab

7 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

atogepant

Narrow target profileApprovedAntagonist

Calcitonin gene-related peptide type 1 receptor antagonist

Indicated for Migraine Disorders

Direct interaction with this protein · Only this protein recorded as a target

erenumab

Narrow target profileApprovedAntagonist

Calcitonin gene-related peptide type 1 receptor antagonist

Indicated for Migraine Disorders

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CALCRL

Gene-level evidence surfaced through the gene CALCRLthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Migraine Disorders

0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Hypertension

0.73Moderately supported

Genetic evidence dominant · Open Targets 0.44

Essential Hypertension

0.67Moderately supported

Genetic evidence dominant · Open Targets 0.41

Coronary Artery Disease

0.64Moderately supported

Genetic evidence dominant · Open Targets 0.34

Obesity disorder

0.62Moderately supported

Genetic evidence dominant · Open Targets 0.37

View evidence synthesis (5)

Migraine DisordersWell supported

0.75

agreement 0.60–0.91

Clinical95%Literature5%

Open Targets aggregate 0.61 · 2 independent evidence families

HypertensionModerately supported

0.73

agreement 0.59–0.86

Genetic97%Literature4%

Open Targets aggregate 0.44 · 2 independent evidence families

Essential HypertensionModerately supported

0.67

agreement 0.54–0.81

Genetic98%Literature2%

Open Targets aggregate 0.41 · 2 independent evidence families

Coronary Artery DiseaseModerately supported

0.64

agreement 0.53–0.75

Genetic56%Clinical40%Literature4%

Open Targets aggregate 0.34 · 3 independent evidence families

Obesity disorderModerately supported

0.62

agreement 0.51–0.73

Genetic85%Clinical14%Literature1%

Open Targets aggregate 0.37 · 3 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Migraine Disorders0.61

Hypertension0.44

Essential Hypertension0.41

Non-immune hydrops fetalis0.37

Obesity disorder0.37

Coronary Artery Disease0.34

Venous Thromboembolism0.33

Drug development

12 compounds recorded · 7 approved · 5 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

RIMEGEPANTApproval

ERENUMABApproval

ATOGEPANTApproval

DAVALINTIDEPhase 2

BI-44370Phase 2

UBROGEPANTApproval

OLCEGEPANTPhase 2

RIMEGEPANT SULFATEApproval

MK3207Phase 2

TELCAGEPANTPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Strong

Approved Drug and UniProt loc high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (12)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

increased blood pressureLynch et al. (2017)increased heart rateLynch et al. (2017)decreased blood pressureLynch et al. (2017)decreased gastric emptyingLynch et al. (2017)increased blood glucoseLynch et al. (2017)increased cardiac contractilityLynch et al. (2017)increased painLynch et al. (2017)decreased painLynch et al. (2017)decreased blood calciumLynch et al. (2017)facial flushingLynch et al. (2017)decreased blood phosphateLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Comparative Outcomes of Migraine Preventives and Anti-CGRP Therapies for Tinnitus in Patients With Migraine: A Randomized Active-Comparator Controlled Trial (COMPACT-PM)PHASE4

NOT_YET_RECRUITING · via erenumab · NCT07655440

A Comparative Effectiveness Study of Oral Medications Used for Migraine Prevention: The APT Comparison StudyPHASE4

RECRUITING · via atogepant · NCT06972056

A Phase 3, Multicenter, 12-Week, Double Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Atogepant for the Preventive Treatment of Chronic Migraine in Pediatric Subjects 12 to 17 Years of AgePHASE3

RECRUITING · via atogepant · NCT06810505

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension to Evaluate the Efficacy, Safety, and Tolerability of Atogepant for the Preventive Treatment of Menstrual MigrainePHASE3

ACTIVE_NOT_RECRUITING · via atogepant · NCT06806293

View all trials (26)

Randomized, Double-blind, Placebo-Controlled, Multiple-Attack Study With an Open-Label Extension to Evaluate the Efficacy, Safety, Tolerability, and the Consistency of Effect of Atogepant for the Acute Treatment of Migraine (ECLIPSE)PHASE3

ACTIVE_NOT_RECRUITING · via atogepant · NCT06241313

A Multicenter, Open-label, Extension Study to Evaluate the Long-term Safety and Tolerability of Atogepant in Pediatric Subjects 6 to 17 Years of Age With MigrainePHASE3

ENROLLING_BY_INVITATION · via atogepant · NCT05707949

A Phase 3, Multicenter, 12-Week, Double Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Atogepant for the Preventive Treatment of Episodic Migraine in Pediatric Subjects 6-17 Years of Age.PHASE3

RECRUITING · via atogepant · NCT05711394

A Phase 4, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of the Concomitant Use of Ubrogepant for the Acute Treatment of Migraine in Subjects Taking Atogepant for the Preventive Treatment of Episodic MigrainePHASE4

COMPLETED · via atogepant · NCT05264129

An Exploratory, Prospective, Randomized, Pragmatic Open Label Cohort Study to Evaluate the Comparative Effectiveness of Eptinezumab in the United StatesPHASE4

TERMINATED · via erenumab · NCT05284019

Phase 4, Open-label Study to Evaluate Treatment Satisfaction With Erenumab in Patients With MigrainePHASE4

COMPLETED · via erenumab · NCT04825678

Biomarker and Genetic Predictors of Erenumab Treatment Response, a Phase 4 Investigational Open-label Study (INTERROGATE)PHASE4

COMPLETED · via erenumab · NCT04265755

Registry for Migraine - Structural and Functional Magnetic Resonance Imaging Before and After Erenumab TreatmentPHASE4

UNKNOWN · via erenumab · NCT04674020

Hypersensitivity to CGRP as a Predictive Biomarker of Migraine Prevention With ErenumabPHASE4

UNKNOWN · via erenumab · NCT04592952

A Phase 4 Single-Blind Study of Gastrointestinal Transit Time in Adult Patients With Migraine Before and After Initiation of a mAb CGRP AntagonistPHASE4

COMPLETED · via erenumab · NCT04294147

Registry for Migraine - Clinical CorePHASE4

UNKNOWN · via erenumab · NCT04603976

Comprehensive Assessment of Erenumab Efficacy in Subjects With High Frequency Episodic Migraine With at Least 1 Previously Failed Preventive Treatment: a Global, Double-blind, Placebo-controlled Phase 4 StudyPHASE4

COMPLETED · via erenumab · NCT04252742

Effect of Erenumab-aooe on Disability and Work Productivity in Employed Subjects With Episodic Migraine Who Have Previously Failed 1 or More Migraine Preventive Treatments.PHASE4

TERMINATED · via erenumab · NCT03912337

A Phase 4, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Chronic Migraine and Medication Overuse HeadachePHASE4

COMPLETED · via erenumab · NCT03971071

Assessment of Prolonged Safety and tOLerability of in Migraine Patients in a Long-term OpeN-label StudyPHASE4

COMPLETED · via erenumab · NCT04084314

A RandomizEd, Double-blind, Cross-over Study to Assess Erenumab effecT on BRAIN Networks Function and Structure in Comparison to Placebo in Episodic Migraine PatientsPHASE4

COMPLETED · via erenumab · NCT03977649

Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient ImprovementPHASE4

COMPLETED · via erenumab · NCT03773562

Head-to-head Study of Erenumab Against topiRamate-a Double-blind, Double Dummy Migraine Study to Assess Tolerability and Efficacy in a patiEnt -Centered SettingPHASE4

COMPLETED · via erenumab · NCT03828539

A Randomized, Double-Blind, Parallel-Group, Active Controlled Trial With Open-Label Safety Extension to Evaluate the Tolerability, Safety, and Efficacy of Atogepant Versus Topiramate in Subjects Requiring Preventive Treatment of Migraine (TEMPLE)PHASE3

COMPLETED · via atogepant · NCT05748483

A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With An Active Treatment Extension to Evaluate the Efficacy, Safety, and Tolerability of Oral Atogepant for the Prevention of Migraine in Japanese Subjects With Episodic MigrainePHASE3

COMPLETED · via atogepant · NCT05861427

A Phase 3 Multicenter 24-Week Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Atogepant When Added to OnabotulinumtoxinA (BOTOX) for the Preventive Treatment of Chronic MigrainePHASE3

COMPLETED · via atogepant · NCT05216263

A Phase 3, Multicenter, Open-Label, 12-Week Study to Evaluate the Safety and Tolerability of Oral Atogepant for the Prevention of Migraine in Chinese Participants With Chronic MigrainePHASE3

COMPLETED · via atogepant · NCT04829747

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral Atogepant for the Prophylaxis of Migraine in Participants With Episodic Migraine Who Have Previously Failed 2 to 4 Classes of Oral Prophylactic Treatments (ELEVATE)PHASE3

COMPLETED · via atogepant · NCT04740827

A Phase 3, Multicenter, Open-Label 156-Week Extension Study To Evaluate The Long-Term Safety And Tolerability Of Oral Atogepant For The Prevention Of Migraine In Participants With Chronic Or Episodic MigrainePHASE3

COMPLETED · via atogepant · NCT04686136

A Phase 3, Multicenter, Open-Label 52-Week Extension Study to Evaluate the Long-Term Safety and Tolerability of Oral Atogepant for the Prevention of Migraine in Japanese Participants With Chronic or Episodic MigrainePHASE3

COMPLETED · via atogepant · NCT04437433

Investigational Use of Erenumab for the Treatment of Fibromyalgia PainPHASE3

WITHDRAWN · via erenumab · NCT06411067

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Regulatory approval2023-08-11
Approval: Aquipta (EMA)
ema · regulatory · ema · via atogepant
Regulatory approval2018-07-26
Approval: Aimovig (EMA)
ema · regulatory · ema · via erenumab

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.