Protein / target
Peroxisome proliferator-activated receptor alpha
Protein at a glance
Biological role
Mitogen-activated protein kinase kinase kinase binding
Primary system
Endocrine & metabolic
Strongest disease association
type 2 diabetes mellitus
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
10 approved · 17 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
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
Domains and Gene Ontology detail (73)Hide
Domains & features
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
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
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
Nuclear receptor signalling
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
- ·nuclear receptor activity
- ·Nuclear Receptor transcription pathway
Metabolic enzyme activity
- ·fatty acid metabolic process
- ·lipoprotein metabolic process
- ·nitric oxide metabolic process
- ·positive regulation of fatty acid metabolic process
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
Cell adhesion
- ·negative regulation of leukocyte cell-cell adhesion
View underlying pathways (13)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Peroxisome proliferator-activated receptor alpha agonist
Appears in clinical studies involving type 2 diabetes mellitus, Hypercholesterolemia, Abnormal circulating lipid concentration, familial hyperlipidemia
Peroxisome proliferator-activated receptor alpha agonist
Appears in clinical studies involving cardiovascular disorder, Abdominal pain, coronary artery disorder, familial hyperlipidemia
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,977 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 27 total
cardiovascular disorder · inherited lipid metabolism disorder · diabetic macular edema
cardiovascular disorder · hyperlipidemia · familial hyperlipidemia
type 2 diabetes mellitus · type 2 diabetes mellitus · Insulin resistance
biliary liver cirrhosis · cholangitis · metabolic dysfunction-associated steatohepatitis
type 1 diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus
cardiovascular disorder · hyperlipoproteinemia
hypertriglyceridemia · metabolic dysfunction-associated steatohepatitis
Hypercholesterolemia · type 2 diabetes mellitus · cardiovascular disorder
cardiovascular disorder · hyperlipoproteinemia type 3
Hepatic fibrosis · metabolic dysfunction-associated steatohepatitis · systemic sclerosis
Tractability
Safety liabilities
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.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Related literature
Papers indexed under “PPAR alpha” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Product recall
Recall (Class II): FENOFIBRATE
- New publicationNeuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms.
- New publicationThe Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer's Disease and Other Neurodegenerative Disorders.
- New publicationFenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension.
- New publicationGemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir.
- New publicationGemfibrozil 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.
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.