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Protein / target

Calcitonin gene-related peptide 1

Encoded byCALCAP06881Homo sapiensSwiss-Prot
UniProt: P06881Ensembl: ENSG00000110680HGNC: HGNC:1437NCBI Gene: 796
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Protein-containing complex binding

Strongest disease association

Migraine Disorders

Via encoding gene CALCA · Genetic evidence · score 0.71

Therapeutic position

Established drug target

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

CGRP1/CALCA is a peptide hormone that induces vasodilation mediated by the CALCRL-RAMP1 receptor complex.

View complete UniProt function annotation

CGRP1/CALCA is a peptide hormone that induces vasodilation mediated by the CALCRL-RAMP1 receptor complex (PubMed:1318039, PubMed:33602864, PubMed:9620797). Dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role (PubMed:3492492). It also elevates platelet cAMP (PubMed:1318039). CGRP1 can also bind and activate CALCR-RAMP1 (AMYR1) receptor complex (PubMed:38603770)

Subcellular location

Secreted
Domains and Gene Ontology detail (30)

Gene Ontology

  • Ccytoplasm
  • Cextracellular region
  • Cextracellular space
  • Fhormone activity
  • Fprotein-containing complex binding
  • Fsignaling receptor binding
  • Pactivation of adenylate cyclase activity
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway
  • Pamylin receptor 1 signaling pathway
  • Pcalcitonin gene-related peptide receptor signaling pathway
  • Pcell-cell signaling
  • Pendothelial cell migration

128 aa · 14 kDa · 3 isoforms

Biological roles

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

Cell migrationGOG protein-coupled signallingGOImmune signallingGO
View supporting evidence

Cell migration

  • ·endothelial cell migration

G protein-coupled signalling

  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • ·G protein-coupled receptor internalization
  • ·phospholipase C-activating G protein-coupled receptor signaling pathway

Immune signalling

  • ·positive regulation of interleukin-1 alpha production
  • ·positive regulation of interleukin-8 production

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

Approved medicines with mapped indications

3 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 Disorders3 medicines
eptinezumabfremanezumabgalcanezumab

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

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.

eptinezumab
ApprovedInhibitor

Calcitonin gene-related peptide inhibitor

Indicated for Migraine Disorders

Acts on a complex — shared with CALCB · 1 of 2 recorded protein targets — narrow recorded profile

galcanezumab
ApprovedInhibitor

Calcitonin gene-related peptide inhibitor

Indicated for Migraine Disorders

Acts on a complex — shared with CALCB · 1 of 2 recorded protein targets — narrow recorded profile

fremanezumab
ApprovedAntagonist

Calcitonin gene-related peptide antagonist

Indicated for Migraine Disorders

Acts on a complex — shared with CALCB · 1 of 2 recorded protein targets — narrow recorded profile

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 CALCA

Gene-level evidence surfaced through the gene CALCA that 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
0.94Well supported

Clinical evidence dominant · Open Targets 0.72

COVID-19
0.58Moderately supported

Genetic evidence dominant · Open Targets 0.35

Immunoglobulin Light-chain Amyloidosis
0.41Preliminary

Pathway evidence dominant · Open Targets 0.47 · no direct causal or clinical evidence

Neurodegenerative Diseases
0.18Preliminary

Pathway evidence dominant · Open Targets 0.26 · no direct causal or clinical evidence

Infections
0.15Preliminary

Literature evidence dominant · Open Targets 0.12 · no direct causal or clinical evidence

View evidence synthesis (5)
Migraine DisordersWell supported
0.94
agreement 0.83–1.00
Clinical46%Genetic45%Literature9%

Open Targets aggregate 0.72 · 3 independent evidence families

COVID-19Moderately supported
0.58
agreement 0.44–0.72
Genetic82%Literature18%

Open Targets aggregate 0.35 · 2 independent evidence families

Immunoglobulin Light-chain AmyloidosisPreliminary
0.41
agreement 0.27–0.55
Pathway66%Animal model28%Literature6%

Open Targets aggregate 0.47 · 3 independent evidence families · no direct causal or clinical evidence

Neurodegenerative DiseasesPreliminary
0.18
agreement 0.00–0.36
Pathway92%Literature8%

Open Targets aggregate 0.26 · 2 independent evidence families · no direct causal or clinical evidence

InfectionsPreliminary
0.15
agreement 0.00–0.42
Literature100%

Open Targets aggregate 0.12 · 1 independent evidence family · no direct causal or clinical evidence

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 Disorders0.72
Immunoglobulin Light-chain Amyloidosis0.47
COVID-190.35
Neurodegenerative Diseases0.26
Infections0.12

Drug development

3 compounds recorded · 3 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (3)
EPTINEZUMABApproval
GALCANEZUMABApproval
FREMANEZUMABApproval

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 — Emerging

Feasibility evidence (structure with ligand and druggable family) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Structure with LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMM

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

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 galcanezumab · NCT07655440

Interventional, Open-label Trial, Investigating the Effectiveness of Eptinezumab in Participants With Migraine and Previous Inadequate Response to CGRP-targeting TherapiesPHASE4

ACTIVE_NOT_RECRUITING · via eptinezumab · NCT06701526

A Single Center, Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Fremanezumab (675 mg Quarterly) in Female Patients Aged 18-45 With Menstrual MigrainePHASE4

COMPLETED · via fremanezumab · NCT06173661

Prevention of Chronic Headache in Patients Diagnosed With Idiopathic Intracranial Hypertension With a Monoclonal Anti-calcitonin Gene-related Peptide Antibody: A Double-blinded Randomized Placebo-controlled Multicentre TrialPHASE3

NOT_YET_RECRUITING · via eptinezumab · NCT07645833

View all trials (26)
EarLy Infusion of Eptinezumab for TreatmEnt of ACute Post-Traumatic Headaches (ELITE-ACT): a Parallel Group, Randomized, Double Blind, Placebo Controlled TrialPHASE3

NOT_YET_RECRUITING · via eptinezumab · NCT07191145

Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intravenous (IV) Eptinezumab in Paediatric Patients (6 to 17 Years) for the Preventive Treatment of Episodic MigrainePHASE3

RECRUITING · via eptinezumab · NCT05897320

Long-term, Open-label (Dose-blinded), Extension Study of Eptinezumab in Children and Adolescents With Chronic or Episodic MigrainePHASE3

RECRUITING · via eptinezumab · NCT05164172

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of IV Eptinezumab in Adolescents (12-17 Years) for the Preventive Treatment of Chronic MigrainePHASE3

RECRUITING · via eptinezumab · NCT04965675

A Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Adolescent Patients 12 to 17 Years of Age With Chronic Migraine - the REBUILD-2 StudyPHASE3

ACTIVE_NOT_RECRUITING · via galcanezumab · NCT04616326

A Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Patients 6 to 17 Years of Age With Episodic Migraine - the REBUILD-1 StudyPHASE3

ACTIVE_NOT_RECRUITING · via galcanezumab · NCT03432286

An Investigator Initiated Trial Evaluating the Therapeutic Efficacy of Galcanezumab in Patients With Alzheimer's DiseaseEARLY_PHASE1

RECRUITING · via galcanezumab · NCT07323927

TOGETHER STUDY: Tandem OnabotulinumtoxinA Galcanezumab Emerging Therapeutic Headache Elimination Research StudyPHASE4

TERMINATED · via galcanezumab · NCT05492695

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of add-on Eptinezumab Treatment to Brief Educational Intervention for the Preventive Treatment of Migraine in Patients With Dual Diagnosis of Migraine and Medication Overuse HeadachePHASE4

COMPLETED · via eptinezumab · NCT05452239

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

TERMINATED · via eptinezumab · NCT05284019

A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Galcanezumab Versus Rimegepant in Adult Participants With Episodic MigrainePHASE4

COMPLETED · via galcanezumab · NCT05127486

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 galcanezumab · NCT04294147

Anti-CGRP Neutralizing Antibody for Modulation of Neurogenic Inflammation in Trigeminal and Glossopharyngeal Pain Associated With Small Fiber Neuropathy/FibromyalgiaPHASE4

COMPLETED · via galcanezumab · NCT04158752

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Extension to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive DisorderPHASE4

COMPLETED · via fremanezumab · NCT04041284

Eptinezumab as an Adjunct to Standard of Care for MIGRANE in an Acute EmeRgency Context (Migraine ERase Study)PHASE3

UNKNOWN · via eptinezumab · NCT06428838

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study With an Open-Label Treatment Period of Fremanezumab Administered Subcutaneously Monthly or Quarterly for the Preventive Treatment of Migraine in Adult Chinese PatientsPHASE3

COMPLETED · via fremanezumab · NCT05458011

Interventional, Open-label, Fixed-dose, Long-term Extension Study to Evaluate Safety of Eptinezumab as Preventive Treatment in Patients With MigrainePHASE3

COMPLETED · via eptinezumab · NCT05064371

Interventional, Open-label, Fixed-dose Multiple Administration Study to Evaluate Long-term Treatment With Eptinezumab in Patients With Chronic Cluster HeadachePHASE3

COMPLETED · via eptinezumab · NCT05064397

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate Efficacy and Safety of Eptinezumab for the Preventive Treatment of MigrainePHASE3

COMPLETED · via eptinezumab · NCT04921384

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Eptinezumab for the Preventive Treatment of Migraine in Patients With a Dual Diagnosis of Migraine and Medication Overuse HeadachePHASE3

COMPLETED · via eptinezumab · NCT04772742

Interventional, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Delayed-Start Study to Evaluate the Efficacy and Safety of Eptinezumab in Patients With Episodic Cluster HeadachePHASE3

COMPLETED · via eptinezumab · NCT04688775

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Chronic Migraine in Pediatric Patients 6 to 17 Years of AgePHASE3

COMPLETED · via fremanezumab · NCT04464707

A Multicenter, Open-Label Study Evaluating the Long-Term Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of Fremanezumab for the Preventive Treatment of Episodic and Chronic Migraine in Pediatric Patients 6 to 17 Years of AgePHASE3

COMPLETED · via fremanezumab · NCT04530110

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Episodic Migraine in Pediatric Patients 6 to 17 Years of AgePHASE3

COMPLETED · via fremanezumab · NCT04458857

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With an Extension Period to Evaluate the Efficacy and Safety of Eptinezumab for the Prevention of Migraine in Patients With Unsuccessful Prior Preventive TreatmentsPHASE3

COMPLETED · via eptinezumab · NCT04418765

A Parallel Group, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Subjects Experiencing an Acute Attack of MigrainePHASE3

COMPLETED · via eptinezumab · NCT04152083

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 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.

  1. Trial status changed2026-08-26

    A Single Center, Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Fremanezumab (675 mg Quarterly) in Female Patients Aged 18-45 With Menstrual Migraine

    Status changed to Completed · ClinicalTrials.gov · via fremanezumab

  2. Label change2026-06-05

    Label change: EPTINEZUMAB-JJMR (BLA761119)

    fda · regulatory · fda · via eptinezumab

  3. Label change2026-06-05

    Label change: FREMANEZUMAB-VFRM (BLA761089)

    fda · regulatory · fda · via fremanezumab

  4. Label change2026-06-05

    Label change: GALCANEZUMAB-GNLM (BLA761063)

    fda · regulatory · fda · via galcanezumab

  5. Indication expanded2025-10-22

    Indication expansion: EPTINEZUMAB-JJMR (BLA761119)

    fda · regulatory · fda · via eptinezumab

  6. Indication expanded2025-08-18

    Indication expansion: EPTINEZUMAB-JJMR (BLA761119)

    fda · regulatory · fda · via eptinezumab

  7. Indication expanded2025-08-05

    Indication expansion: FREMANEZUMAB-VFRM (BLA761089)

    fda · regulatory · fda · via fremanezumab

  8. Label change2025-03-21

    Label change: EPTINEZUMAB-JJMR (BLA761119)

    fda · regulatory · fda · via eptinezumab

  9. Label change2025-03-21

    Label change: EPTINEZUMAB-JJMR (BLA761119)

    fda · regulatory · fda · via eptinezumab

  10. Label change2025-03-21

    Label change: FREMANEZUMAB-VFRM (BLA761089)

    fda · regulatory · fda · via fremanezumab

  11. Label change2025-03-21

    Label change: GALCANEZUMAB-GNLM (BLA761063)

    fda · regulatory · fda · via galcanezumab

  12. Regulatory approval2022-01-24

    Approval: Vyepti (EMA)

    ema · regulatory · ema · via eptinezumab

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.