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Protein / target

Alpha-1D adrenergic receptor

Encoded byADRA1DP25100Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
55
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Alpha1-adrenergic receptor

Primary biology

GPCR signalling

Strongest disease association

Hypertension

Via encoding gene ADRA1D · Genetic evidence · score 0.35

Therapeutic position

Established drug target

Small molecules

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

Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11).

View complete UniProt function annotation

Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C (PubMed:7746284). ADRA1D binds the catecholamine ligands norepinephrine and epinephrine (PubMed:7815325, PubMed:8024574, PubMed:8183249)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (13)

Gene Ontology

  • Cplasma membrane
  • Falpha1-adrenergic receptor activity
  • Fidentical protein binding
  • Padenylate cyclase-activating adrenergic receptor signaling pathway
  • Padenylate cyclase-modulating G protein-coupled receptor signaling pathway
  • Pcell-cell signaling
  • PG protein-coupled receptor signaling pathway
  • Pneuron-glial cell signaling
  • Pphospholipase C-activating G protein-coupled receptor signaling pathway
  • Ppositive regulation of cell population proliferation
  • Ppositive regulation of cytosolic calcium ion concentration
  • Ppositive regulation of MAPK cascade

572 aa · 60 kDa

Biological roles

Reactome v97

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

Cell proliferation & survivalGOG protein-coupled signallingUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

G protein-coupled signalling

  • ·Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that sig…
  • ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  • ·G protein-coupled receptor signaling pathway
  • ·phospholipase C-activating G protein-coupled receptor signaling pathway
View underlying pathways (3)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GNAQGNA11GNA13GNA12ADRA1BADRA1ASNTB2SNTB1UTRNTBXA2RADRA1D

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

2 medicines · 15 areas

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.

Angioedema1 medicine
Asthma1 medicine
Glaucoma1 medicine
Heart Arrest1 medicine
Heart Failure1 medicine
Hemorrhage1 medicine
Hypersensitivity1 medicine
Hypertension1 medicine
Lung Diseases, Obstructive1 medicine
Myocardial Infarction1 medicine
Shock, Septic1 medicine
Sinusitis1 medicine
Urticaria1 medicine
Ventricular Dysfunction, Left1 medicine
Broader indication categories (1)
Cardiovascular Diseases2 medicines

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

55 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

2

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.

carvedilol
ApprovedAntagonist

Adrenergic receptor alpha-1 antagonist

Indicated for Heart Failure, Hypertension, Myocardial Infarction, Ventricular Dysfunction, Left

Acts on a complex — shared with ADRA1B, ADRA1A · 1 of 6 recorded protein targets

Epinephrine
ApprovedAgonist

Adrenergic receptor agonist

Indicated for Angioedema, Asthma, Glaucoma, Heart Arrest

Acts on a complex — shared with ADRA1A, ADRA2A, ADRB2 +5 more · 1 of 9 recorded protein targets — broad pharmacology

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 ADRA1D

Gene-level evidence surfaced through the gene ADRA1Dthat 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.

Hypertension
0.84Well supported

Clinical evidence dominant · Open Targets 0.66

Death, Sudden, Cardiac
0.75Well supported

Clinical evidence dominant · Open Targets 0.59

Benign prostatic hyperplasia
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Myocardial Infarction
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (4)
HypertensionWell supported
0.84
agreement 0.740.95
Clinical65%Genetic30%Literature5%

Open Targets aggregate 0.66 · 3 independent evidence families

Death, Sudden, CardiacWell supported
0.75
agreement 0.610.89
Clinical88%Animal model13%

Open Targets aggregate 0.59 · 2 independent evidence families

Benign prostatic hyperplasiaWell supported
0.75
agreement 0.600.91
Clinical98%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

Myocardial InfarctionModerately supported
0.74
agreement 0.590.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 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
Hypertension0.66
Benign prostatic hyperplasia0.61
Myocardial Infarction0.60
Death, Sudden, Cardiac0.59

Drug development

59 compounds recorded · 55 approved · 3 in clinical development · 1 earlier-stage

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)
EPHEDRINEApproval
LABETALOLApproval
NAFTOPIDILApproval
XYLOMETAZOLINEApproval
OXYMETAZOLINEApproval
AVIPTADILPhase 3
BUCINDOLOLPhase 3
TETRAHYDROZOLINEApproval
METHOXAMINEApproval
EPHEDRINE SULFATEApproval

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 moleculesStrong

Approved Drug and High-Quality Ligand support this modality.

AntibodiesEmerging

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

Protein degradersEmerging

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

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (8)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Approved Drug

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.

View all trials (26)

RECRUITING · via carvedilol · NCT05931276

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 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.

  1. Regulatory approval2026-07-31

    Approval: EPINEPHRINE (ANDA217426)

    fda · regulatory · fda · via Epinephrine

  2. Label change2026-06-22

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  3. Product recall2026-05-14

    Recall (Class III): EPINEPHRINE

    fda · safety · fda · via Epinephrine

  4. Regulatory approval2024-08-22

    Approval: Eurneffy (EMA)

    ema · regulatory · ema · via Epinephrine

  5. New publication2023-11-07
    Impact of norepinephrine on immunity and oxidative metabolism in sepsis.

    Frontiers in immunology · 2023 · 33 citations · Europe PMC · via Epinephrine

  6. New publication2023-09-25
    Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

    Circulation · 2023 · 53 citations · Europe PMC · via carvedilol

  7. Label change2023-01-05

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  8. Supplemental approval2021-08-17

    Supplemental approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  9. New publication2019-10-31
    The effect of topical epinephrine 1:1000 with and without infiltration of 1% lidocaine with epinephrine 1:100,000 on endoscopic surgical field visualization: a double-blind randomized controlled study.

    International forum of allergy & rhinology · 2020 · 6 citations · Europe PMC · via Epinephrine

  10. Indication expanded2019-01-29

    Indication expansion: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  11. Regulatory approval2013-12-18

    Approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  12. New publication1996-05-01
    The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group.

    The New England journal of medicine · 1996 · 2,888 citations · Europe PMC · via carvedilol

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.