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Protein / target

Peroxisome proliferator-activated receptor alpha

Encoded byPPARAQ07869Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
10
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Mitogen-activated protein kinase kinase kinase binding

Strongest disease association

Diabetes Mellitus, Type 2

Via encoding gene PPARA · Genetic evidence · score 0.24

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

5 papers · latest 2024

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

Ligand-activated transcription factor.

View complete UniProt function annotation

Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as a transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2

Subcellular location

Nucleus
Domains and Gene Ontology detail (73)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Cfibrillar center
  • Cnuclear body
  • Cnucleoplasm
  • Cnucleus
  • CRNA polymerase II transcription regulator complex
  • FDNA binding
  • FDNA-binding transcription activator activity
  • FDNA-binding transcription activator activity, RNA polymerase II-specific
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • FDNA-binding transcription repressor activity, RNA polymerase II-specific

468 aa · 52 kDa · 2 isoforms

Biological roles

Reactome v97

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

Nuclear receptor signallingUniProt · GO · ReactomeLipid & lipoprotein metabolismUniProt · GOTranscriptional regulationUniProt · GO · ReactomeKinase signallingGOImmune signallingGO
View supporting evidence

Nuclear receptor signalling

  • ·Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by t…
  • ·nuclear receptor activity
  • ·Nuclear Receptor transcription pathway

Lipid & lipoprotein metabolism

  • ·Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by t…
  • ·fatty acid metabolic process
  • ·lipoprotein metabolic process
  • ·negative regulation of cholesterol storage

Transcriptional regulation

  • ·Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by t…
  • ·RNA polymerase II transcription regulator complex
  • ·DNA-binding transcription activator activity
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific

Kinase signalling

  • ·mitogen-activated protein kinase kinase kinase binding
  • ·negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Immune signalling

  • ·negative regulation of cytokine production involved in inflammatory response
  • ·negative regulation of inflammatory response
View underlying pathways (13)

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.

RXRAPPARGC…NCOA1NCOR2NCOR1PER2JUNLPIN1XPR1FABP1PPARA

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

3 medicines · 9 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.

Abdominal Pain1 medicine
Cholangitis1 medicine
Coronary Disease1 medicine
Diabetes Mellitus1 medicine
Diabetes Mellitus, Type 21 medicine
Dyslipidemias1 medicine
Hypercholesterolemia1 medicine
Hypothyroidism1 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.

10 medicines meet Open Targets' target-level approved-medicine definition; the 3 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

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.

Fenofibrate
Narrow target profileApprovedAgonist

Peroxisome proliferator-activated receptor alpha agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2, Dyslipidemias, Hypercholesterolemia

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

Gemfibrozil
Narrow target profileApprovedAgonist

Peroxisome proliferator-activated receptor alpha agonist

Indicated for Abdominal Pain, Coronary Disease, Cardiovascular Diseases

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

elafibranor
Narrow target profileApprovedAgonist

Peroxisome proliferator-activated receptor alpha agonist

Indicated for Cholangitis

Direct interaction with this protein · 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 PPARA

Gene-level evidence surfaced through the gene PPARAthat 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.

Diabetes Mellitus, Type 2
0.80Well supported

Clinical evidence dominant · Open Targets 0.63

Cardiovascular Diseases
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.59

Inherited lipid metabolism disorder
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

Hyperlipidemias
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.55

Primary biliary cholangitis
0.62Moderately supported

Clinical evidence dominant · Open Targets 0.44

View evidence synthesis (5)
Diabetes Mellitus, Type 2Well supported
0.80
agreement 0.690.91
Clinical70%Genetic23%Literature7%

Open Targets aggregate 0.63 · 3 independent evidence families

Cardiovascular DiseasesModerately supported
0.72
agreement 0.570.88
Clinical96%Literature5%

Open Targets aggregate 0.59 · 2 independent evidence families

Inherited lipid metabolism disorderModerately supported
0.70
agreement 0.550.86
Clinical97%Literature3%

Open Targets aggregate 0.57 · 2 independent evidence families

HyperlipidemiasModerately supported
0.69
agreement 0.540.84
Clinical95%Literature5%

Open Targets aggregate 0.55 · 2 independent evidence families

Primary biliary cholangitisModerately supported
0.62
agreement 0.500.75
Clinical68%Animal model18%Literature14%

Open Targets aggregate 0.44 · 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
Diabetes Mellitus, Type 20.63
Cardiovascular Diseases0.59
Inherited lipid metabolism disorder0.57
Hyperlipidemias0.55
Primary biliary cholangitis0.44
Combined hyperlipidemia0.42
Coronary Artery Disease0.42

Drug development

27 compounds recorded · 10 approved · 17 in clinical development

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 (10)
CHOLINE FENOFIBRATEApproval
PEMAFIBRATEApproval
CHIGLITAZARPhase 3
ELAFIBRANORApproval
TESAGLITAZARPhase 3
CIPROFIBRATEApproval
K-877Phase 3
FENOFIBRIC ACIDApproval
CLOFIBRATEApproval
LANIFIBRANORPhase 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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

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

View underlying tractability evidence (7)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

Decrease, Population growth rateAOP-Wikiimpaired, FertilityAOP-WikiMalformation, Male reproductive tractAOP-WikiDecreased, Body WeightAOP-WikiIncreased, Liver SteatosisAOP-Wikiimpaired, FertilityAOP-WikiIncreased, Pancreatic acinar tumorsAOP-Wikinew-onset diabetes after transplantationClinPGxViable offspring, decreasedAOP-Wikiregulation of transcription factor activityToxCastreceptor bindingToxCastIncreased, Liver SteatosisAOP-Wiki

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

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)

ACTIVE_NOT_RECRUITING · via Fenofibrate · NCT06174402

ACTIVE_NOT_RECRUITING · via Fenofibrate · NCT04929379

COMPLETED · via Fenofibrate · NCT06451900

COMPLETED · via Fenofibrate · NCT03829514

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. Label change2026-08-17

    Label change: FENOFIBRATE (ANDA211122)

    fda · regulatory · fda · via Fenofibrate

  2. Label change2026-08-07

    Label change: ELAFIBRANOR (NDA218860)

    fda · regulatory · fda · via elafibranor

  3. Label change2026-08-05

    Label change: FENOFIBRATE (ANDA204475)

    fda · regulatory · fda · via Fenofibrate

  4. Supplemental approval2026-08-04

    Supplemental approval: FENOFIBRATE (ANDA208476)

    fda · regulatory · fda · via Fenofibrate

  5. Product recall2026-05-28

    Recall (Class II): FENOFIBRATE

    fda · safety · fda · via Fenofibrate

  6. Supplemental approval2025-08-07

    Supplemental approval: FENOFIBRATE (ANDA208476)

    fda · regulatory · fda · via Fenofibrate

  7. Regulatory approval2024-09-19

    Approval: Iqirvo (EMA)

    ema · regulatory · ema · via elafibranor

  8. Regulatory approval2024-06-10

    Approval: ELAFIBRANOR (NDA218860)

    fda · regulatory · fda · via elafibranor

  9. New publication2023-10-30
    Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms.

    CNS neuroscience & therapeutics · 2024 · 16 citations · Europe PMC · via Gemfibrozil

  10. New publication2020-03-13
    The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer's Disease and Other Neurodegenerative Disorders.

    Neurochemical research · 2020 · 233 citations · Europe PMC · via Fenofibrate

  11. New publication2013-04-01
    Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension.

    Journal of hypertension · 2013 · 33 citations · Europe PMC · via Fenofibrate

  12. New publication1999-08-01
    Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.

    The New England journal of medicine · 1999 · 2,104 citations · Europe PMC · via Gemfibrozil

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.

Research activity

5 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.

Related family literature

4

Papers about “Peroxisome Proliferator-Activated Receptors” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas.

Souza-Tavares H · World journal of gastroenterology · 2023

via Peroxisome Proliferator-Activated Receptors

Redox regulation of the immune response.

Morris G · Cellular & molecular immunology · 2022

via Peroxisome Proliferator-Activated Receptors

PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice.

Wang Y · International journal of molecular sciences · 2020

via Peroxisome Proliferator-Activated Receptors

Inflammatory links between obesity and metabolic disease.

Lumeng CN · The Journal of clinical investigation · 2011

via Peroxisome Proliferator-Activated Receptors

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.