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Protein / target

Peroxisome proliferator-activated receptor gamma

Encoded byPPARGP37231Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
12
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Transcription cis-regulatory region binding

Strongest disease association

Diabetes Mellitus, Type 2

Via encoding gene PPARG · Genetic literature evidence · score 0.92

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

4 papers · latest 2023

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 that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-oxidation of fatty acids.

View complete UniProt function annotation

Ligand-activated transcription factor that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-oxidation of fatty acids (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Activated by lipid ligands: binds peroxisome proliferators, such as hypolipidemic drugs, and fatty acids, such as prostaglandin J2 metabolites (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Ligand-binding results in a conformational change in the receptor, promoting dissociation of repressors and recruitment of coactivators, and subsequent activation of target gene expression (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Specifically binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase (By similarity). Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses (PubMed:20829347). Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)

Subcellular location

NucleusCytoplasm
Domains and Gene Ontology detail (105)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cnucleoplasm
  • Cnucleus
  • Creceptor complex
  • CRNA polymerase II transcription regulator complex
  • Falpha-actinin binding
  • Farachidonate binding
  • Fchromatin binding
  • FDNA binding
  • FDNA binding domain binding
  • FDNA-binding transcription activator activity, RNA polymerase II-specific

505 aa · 58 kDa · 3 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 · GOCell migrationGOTranscriptional regulationUniProt · GO · ReactomeImmune signallingUniProt · GO
View supporting evidence

Nuclear receptor signalling

  • ·Ligand-activated transcription factor that forms obligate heterodimers with the retinoic…
  • ·nuclear receptor activity
  • ·Nuclear Receptor transcription pathway

Lipid & lipoprotein metabolism

  • ·Ligand-activated transcription factor that forms obligate heterodimers with the retinoic…
  • ·cellular response to low-density lipoprotein particle stimulus
  • ·fatty acid metabolic process
  • ·long-chain fatty acid transport

Cell migration

  • ·negative regulation of blood vessel endothelial cell migration

Transcriptional regulation

  • ·Ligand-activated transcription factor that forms obligate heterodimers with the retinoic…
  • ·RNA polymerase II transcription regulator complex
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific
  • ·DNA-binding transcription factor activity

Immune signalling

  • ·Ligand-activated transcription factor that forms obligate heterodimers with the retinoic…
  • ·beige fat cell differentiation
  • ·brown fat cell differentiation
  • ·fat cell differentiation
View underlying pathways (8)

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.

PPARGC…NCOR1NCOR2RXRAMED1NCOA1CREBBPNCOA2RELASIRT1PPARG

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 · 4 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.

Colitis, Ulcerative1 medicine
Diabetes Mellitus1 medicine
Diabetes Mellitus, Type 21 medicine
Proctitis1 medicine

12 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.

rosiglitazone
Narrow target profileApprovedAgonist

Peroxisome proliferator-activated receptor gamma agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

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

mesalamine
ApprovedAgonist

Peroxisome proliferator-activated receptor gamma agonist

Indicated for Colitis, Ulcerative, Proctitis

Direct interaction with this protein · 1 of 4 recorded protein targets

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 PPARG

Gene-level evidence surfaced through the gene PPARGthat 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
0.98Well supported

Genetic evidence dominant · Open Targets 0.86

Diabetes Mellitus
0.96Well supported

Genetic evidence dominant · Open Targets 0.74

PPARG-related familial partial lipodystrophy
0.89Well supported

Genetic evidence dominant · Open Targets 0.81

Coronary Artery Disease
0.89Well supported

Genetic evidence dominant · Open Targets 0.55

Metabolic Syndrome
0.86Well supported

Genetic evidence dominant · Open Targets 0.51

View evidence synthesis (5)
Diabetes Mellitus, Type 2Well supported
0.98
agreement 0.881.00
Genetic44%Clinical37%Animal model12%Literature7%Genetic literaturedup

Open Targets aggregate 0.86 · 4 independent evidence families · 1 not counted as duplicate

Diabetes MellitusWell supported
0.96
agreement 0.861.00
Genetic43%Clinical38%Animal model13%Literature7%

Open Targets aggregate 0.74 · 4 independent evidence families

PPARG-related familial partial lipodystrophyWell supported
0.89
agreement 0.771.00
Genetic76%Animal model22%Literature3%Genetic literaturedup

Open Targets aggregate 0.81 · 3 independent evidence families · 1 not counted as duplicate

Coronary Artery DiseaseWell supported
0.89
agreement 0.790.99
Genetic53%Clinical29%Literature10%Animal model9%

Open Targets aggregate 0.55 · 4 independent evidence families

Metabolic SyndromeWell supported
0.86
agreement 0.760.96
Genetic48%Clinical33%Animal model10%Literature9%

Open Targets aggregate 0.51 · 4 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 20.86
PPARG-related familial partial lipodystrophy0.81
Diabetes Mellitus0.74
Colitis, Ulcerative0.62
Obesity, Morbid0.61
Coronary Artery Disease0.55
Colon carcinoma0.52
Obesity disorder0.52
Metabolic Syndrome0.51

Drug development

40 compounds recorded · 12 approved · 28 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)
MK-0767Phase 3
DB959Phase 2 3
MK-0533Phase 2
LERIGLITAZONEPhase 3
INDEGLITAZARPhase 2
ETALOCIBPhase 2
ATX08-001Phase 2
LANIFIBRANORPhase 3
FARGLITAZARPhase 3
BALSALAZIDE DISODIUMApproval

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 database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

increased inflammationLynch et al. (2017)Increased, Liver SteatosisAOP-Wikiincreased heart weightLynch et al. (2017)receptor bindingToxCastheart failureLynch et al. (2017)regulation of transcription factor activityToxCastobesityAOP-Wikiaspirin hypersensitivityClinPGxincreased plasma volumeLynch et al. (2017)protein stabilizationToxCastdecreased inflammationLynch et al. (2017)increased body weightLynch 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

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 mesalamine · NCT04920149

COMPLETED · via mesalamine · NCT01090102

COMPLETED · via mesalamine · NCT00652145

TERMINATED · via rosiglitazone · NCT00819910

COMPLETED · via rosiglitazone · NCT00567593

COMPLETED · via rosiglitazone · NCT00440375

COMPLETED · via rosiglitazone · NCT00306176

ClinicalTrials.gov via the drug-target graph.

What's happening now

9

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 approval2025-04-14

    Approval: MESALAMINE (ANDA219028)

    fda · regulatory · fda · via mesalamine

  2. New publication2023-10-26
    Risk of Pancreatitis With Incretin Therapies Versus Thiazolidinediones in the Veterans Health Administration.

    The Annals of pharmacotherapy · 2024 · 8 citations · Europe PMC · via rosiglitazone

  3. Safety communication2014-12-11

    Drug Safety Update: Rosiglitazone: recommended withdrawal from clinical use

    mhra · safety · mhra · via rosiglitazone

  4. New publication2014-04-30
    Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2014 · 68 citations · Europe PMC · via mesalamine

  5. New publication2013-04-12
    Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

    PloS one · 2013 · 10 citations · Europe PMC · via rosiglitazone

  6. New publication2011-02-16
    Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.

    The Journal of clinical endocrinology and metabolism · 2011 · 32 citations · Europe PMC · via rosiglitazone

  7. New publication2010-07-02
    Randomized comparison of the effects of rosiglitazone vs. placebo on peak integrated cardiovascular performance, cardiac structure, and function.

    European heart journal · 2010 · 22 citations · Europe PMC · via rosiglitazone

  8. New publication2007-12-07
    Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.

    Gastroenterology · 2008 · 184 citations · Europe PMC · via rosiglitazone

  9. New publication2003-12-01
    Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.

    The Journal of clinical investigation · 2003 · 4,951 citations · Europe PMC · via rosiglitazone

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

4 papers · to 2023

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

Most cited

Barnes PJ · The European respiratory journal · 2009

Khan RS · Hepatology (Baltimore, Md.) · 2019

Korbecki J · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019

Recent

Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease.

Khan RS · Hepatology (Baltimore, Md.) · 2019

The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms.

Korbecki J · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019

Systemic manifestations and comorbidities of COPD.

Barnes PJ · The European respiratory journal · 2009

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.