PPARD

Summary

PPARD (peroxisome proliferator activated receptor delta, HGNC:9235) is a protein-coding gene on chromosome 6p21.31, encoding Peroxisome proliferator-activated receptor delta (Q03181). Ligand-activated transcription factor key mediator of energy metabolism in adipose tissues.

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. The encoded protein is thought to function as an integrator of transcriptional repression and nuclear receptor signaling. It may inhibit the ligand-induced transcriptional activity of peroxisome proliferator activated receptors alpha and gamma, though evidence for this effect is inconsistent. Expression of this gene in colorectal cancer cells may be variable but is typically relatively low. Knockout studies in mice suggested a role for this protein in myelination of the corpus callosum, lipid metabolism, differentiation, and epidermal cell proliferation. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms.

Source: NCBI Gene 5467 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 51 total
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• Transcription factor: yes — 104 downstream targets (CollecTRI)
• MANE Select transcript: NM_006238

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9235
Approved symbol	PPARD
Name	peroxisome proliferator activated receptor delta
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	NUC1, NUCII, FAAR, NR1C2, PPARB
Ensembl gene	ENSG00000112033
Ensembl biotype	protein_coding
OMIM	600409
Entrez	5467

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 42 protein_coding

ENST00000311565, ENST00000337400, ENST00000360694, ENST00000418635, ENST00000448077, ENST00000875334, ENST00000875335, ENST00000875336, ENST00000875337, ENST00000875338, ENST00000875339, ENST00000875340, ENST00000875341, ENST00000875342, ENST00000875343, ENST00000875344, ENST00000875345, ENST00000875346, ENST00000875347, ENST00000875348, ENST00000875349, ENST00000875350, ENST00000875351, ENST00000875352, ENST00000875353, ENST00000875354, ENST00000875355, ENST00000875356, ENST00000917034, ENST00000917035, ENST00000917036, ENST00000950088, ENST00000950089, ENST00000950090, ENST00000950091, ENST00000950092, ENST00000950093, ENST00000950094, ENST00000950095, ENST00000950096, ENST00000950097, ENST00000950098

RefSeq mRNA: 5 — MANE Select: NM_006238 NM_001171818, NM_001171819, NM_001171820, NM_006238, NM_177435

CCDS: CCDS4803, CCDS4804, CCDS54994, CCDS54995

Canonical transcript exons

ENST00000360694 — 8 exons

Exon	Start	End
ENSE00001407360	35342558	35342681
ENSE00003559469	35347067	35347150
ENSE00003890127	35425832	35428178
ENSE00003892036	35421820	35421958
ENSE00003892736	35410987	35411217
ENSE00003893686	35424329	35424779
ENSE00003895445	35420127	35420281
ENSE00003895895	35423946	35424148

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 96.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0912 / max 126.2949, expressed in 1803 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67429	8.1520	1764
67431	4.0874	1256
67430	3.6762	1387
67432	0.1204	34
165261	0.0552	9

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.46	gold quality
cartilage tissue	UBERON:0002418	94.59	gold quality
upper leg skin	UBERON:0004262	93.44	gold quality
buccal mucosa cell	CL:0002336	93.23	gold quality
cauda epididymis	UBERON:0004360	93.23	gold quality
amniotic fluid	UBERON:0000173	93.08	gold quality
right lobe of thyroid gland	UBERON:0001119	92.02	gold quality
left lobe of thyroid gland	UBERON:0001120	91.90	gold quality
thyroid gland	UBERON:0002046	91.65	gold quality
corpus epididymis	UBERON:0004359	91.63	gold quality
mucosa of transverse colon	UBERON:0004991	91.48	gold quality
esophagus mucosa	UBERON:0002469	91.40	gold quality
placenta	UBERON:0001987	90.93	gold quality
stromal cell of endometrium	CL:0002255	90.91	gold quality
secondary oocyte	CL:0000655	90.84	gold quality
colonic mucosa	UBERON:0000317	90.67	gold quality
primary visual cortex	UBERON:0002436	90.67	gold quality
cervix squamous epithelium	UBERON:0006922	90.55	gold quality
right frontal lobe	UBERON:0002810	90.52	gold quality
penis	UBERON:0000989	89.96	gold quality
vagina	UBERON:0000996	89.74	gold quality
gingival epithelium	UBERON:0001949	89.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.54	gold quality
caput epididymis	UBERON:0004358	89.49	gold quality
cingulate cortex	UBERON:0003027	89.35	gold quality
left ovary	UBERON:0002119	89.32	gold quality
anterior cingulate cortex	UBERON:0009835	89.31	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	89.30	gold quality
skin of hip	UBERON:0001554	89.27	gold quality
CA1 field of hippocampus	UBERON:0003881	89.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

104 targets.

Target	Regulation
ACACA	Repression
ACADL	Activation
ACOX1	Unknown
ACSL3	Activation
ACSL6	Activation
ACTG2	Repression
ADAM2
ANG	Repression
ANGPT1	Unknown
ANGPTL3	Repression
ANGPTL4	Repression
APOA2	Activation
APOB	Repression
APOE
APOM	Repression
BCL2	Activation
BCL2L1	Activation
CALR	Activation
CAT	Activation
CCL2	Repression
CD36	Activation
CD74
CEBPA	Repression
CEBPB	Unknown
CERK	Unknown
CNR1	Unknown
CPT1A	Activation
CPT1B	Unknown
CRYBA1	Unknown
CTSE	Activation

JASPAR motifs

Motif	Name	Family
MA1550.1	PPARD	Thyroid hormone receptor-related factors (NR1)
MA1550.2	PPARD	Thyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:8725145

Upstream regulators (CollecTRI, top): AP1, CEBPA, CTCF, CTNNB1, ESR1, FOS, GLI2, JUN, NCOA2, NCOR2, NR6A1, NRIP1, PIN1, RELA, SMAD3, TFAP2A, VDR, YY1

miRNA regulators (miRDB)

94 targeting PPARD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6883-5P	99.69	68.05	3785

Literature-anchored findings (GeneRIF, showing 40)

• differential regulation of vascular endothelial growth factor expression in bladder cancer cells (peroxisome proliferative activated receptor, beta) (PMID:11980898)
• Results suggest that peroxisome proliferator-activated receptor beta overexpression is not an inherent property of breast cancer cell lines, but it may play a role through activation of downstream genes (PPARbeta). (PMID:12009300)
• Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. (PMID:12594814)
• 4 polymorphisms were found: -409C/T (promoter, +73C/T (exon 1), +255A/G (exon 3), & +294T/C (exon 4). An interaction with the PPAR alpha L162V polymorphism was also detected for several lipid parameters. PPARD plays a role in cholesterol metabolism. (PMID:12615676)
• The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells. (PMID:12909723)
• results implicate PPAR-delta in the regulation of intestinal adenoma growth (PMID:14758356)
• Positive associations of PPAR-delta polymorphisms with fasting plasma glucose and BMI detected in nondiabetic control subjects (PMID:14988273)
• gene regulation by PPARdelta in the uterine cells uniquely responds to SRC-2, N-CoR, SMRT, or RIP140, and these interactions may be operative during implantation when these cofactors are abundantly expressed. (PMID:15001550)
• PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates triglyceride accumulation in keratinocytes. (PMID:15102088)
• 11beta-HSD2 is an additional target for PPAR delta, which may regulate human placental function (PMID:15591138)
• This study was performed to determine whether specific activation of PPARdelta has direct effects on insulin action in skeletal muscle. (PMID:15793256)
• COX-2 immunopositivity was significantly associated with PPARbeta and PPARgamma immunoreactivity. Microvessel density was significantly higher among PPARbeta-immunoreactive squamous cell carcinomas. (PMID:15811118)
• the ligand-independent tight control of the position of the PPAR helix 12 provides an effective alternative for establishing an interaction with CoA proteins (PMID:15888456)
• PPARdelta signaling pathways are interconnected at the level of cross-regulation of their respective transcription factor mRNA levels (PMID:15890193)
• PPARdelta expression is up-regulated between the first and third trimester, indicating a role for this nuclear receptor in placental function (PMID:15979543)
• PPARdelta + 294T/C gene polymorphism in subjects with metabolic syndrome may be involved in the occurrence of obesity and dyslipidemia. (PMID:16053787)
• PPARdelta partially rescued prostate epithelial cells from growth inhibition and also dramatically inhibited sulindac sulfide-mediated p21WAF1/CIP1 upregulation. (PMID:16091736)
• PPARdelta +294T/C polymorphism has no influence on plasma lipoprotein concentrations, body mass index or atherosclerotic disease either in healthy subjects or in patients with DM-2, both in males and females. (PMID:16285997)
• Single nucleotide polymorphisms of PPARD primarily affected insulin sensitivity by modifying glucose uptake in skeletal muscle but not in adipose tissue. (PMID:16306381)
• The expression of PPARdelta gene in rectal cancers is not statistically different from normal mucosa. (PMID:16361076)
• Human platelets contain PPARbeta and that its selective activation inhibits platelet aggregation. (PMID:16368717)
• Data describe the activated form of the peroxisome proliferator-activated receptor-beta/delta using a ligand binding domain model. (PMID:16387648)
• overexpressed during the S phase of the cell cycle compared with the G0/1 phase (PMID:16476973)
• This review concludes that PPAR delta has emerged as a powerful metabolic regulator in diverse tissues including fat, skeletal muscle, and the heart. (PMID:16511591)
• PGI2 protects endothelial cells from H2O2-induced apoptosis by inducing PPARdelta binding to 14-3-3alpha promoter, thereby upregulating 14-3-3alpha protein expression. (PMID:16645156)
• data provide further evidence for an involvement of PPARdelta in the regulation of BMI. (PMID:16652134)
• Skeletal muscle mRNA expression of PPAR delta increased in type 2 diabetic patients with an improved clinical profile following low-intensity exercise, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters. (PMID:16752430)
• Single nucleotide polymorphisms in PPARD modify the conversion from glucose intolerance to type 2 diabetes. (PMID:16804087)
• Therefore, these results indicate that induction of fatty acid oxidation with PPARbeta activators during short-term exposition is not sufficient to correct for insulin resistance in muscle cells from type 2 diabetic patients. (PMID:16897074)
• PPARbeta/delta is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. (PMID:17068288)
• PPARD-87T/C polymorphism is associated with higher fasting plasma glucose concentrations in both normal glucose tolerant and diabetic subjects, largely due to impaired insulin sensitivity (PMID:17116180)
• PPAR-delta activation increases cholesterol export and represses inflammatory gene expression in macrophages and atherosclerotic lesions. (PMID:17119917)
• support the rationale for developing PPARdelta antagonists for prevention and/or treatment of cancer (PMID:17148604)
• PPARdelta induces COX-2 expression and the COX-2-derived PGE(2) further activates PPARdelta via cPLA(2)alpha. which forms a growth-promoting signaling that may play a role in hepatocarcinogenesis. (PMID:17178883)
• These studies demonstrate that ligand activation of PPARbeta/delta does not lead to an anti-apoptotic effect in either human or mouse keratinocytes, but rather, leads to inhibition of cell growth likely through the induction of terminal differentiation. (PMID:17254750)
• DNA sequence variation in the PPARdelta locus is a potential modifier of changes in cardiorespiratory fitness and plasma HDL-C in healthy individuals in response to regular exercise. (PMID:17259439)
• The expression of PPARdelta gene in rectal cancers is not statistically different from that in normal mucosa, and it is not correlated with cell differentiation, pathological categories and Dukes stages. (PMID:17294733)
• human aortic smooth muscle cells Prostacyclin 2 synthase(PGIS) gene transfer reduced peroxisome proliferator-activated receptor delta(PPAR-delta) expression and inhibited neointimal formation after balloon injury (PMID:17303142)
• PPAR delta activates 14-3-3 epsilon gene (YWHAE) promoter in human endothelial cells in a concentration and time-dependent manner. (PMID:17303761)
• The activated proinflammatory state of monocytes and MDM in low HDL-C subjects constitutes a novel parameter of risk associated with HDL deficiency, related to altered expression of metallothionein genes and the reciprocal regulation of PPARdelta. (PMID:17322100)

Cross-species orthologs

189 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppardb	ENSDARG00000009473
danio_rerio	pparda	ENSDARG00000044525
mus_musculus	Ppard	ENSMUSG00000002250
rattus_norvegicus	Ppard	ENSRNOG00000000503
drosophila_melanogaster	EcR	FBGN0000546
drosophila_melanogaster	Hr96	FBGN0015240
caenorhabditis_elegans		WBGENE00001062
caenorhabditis_elegans	nhr-2	WBGENE00003601
caenorhabditis_elegans		WBGENE00003608
caenorhabditis_elegans		WBGENE00003611
caenorhabditis_elegans		WBGENE00003614
caenorhabditis_elegans		WBGENE00003615
caenorhabditis_elegans		WBGENE00003617
caenorhabditis_elegans		WBGENE00003618
caenorhabditis_elegans		WBGENE00003620
caenorhabditis_elegans	nhr-23	WBGENE00003622
caenorhabditis_elegans		WBGENE00003624
caenorhabditis_elegans		WBGENE00003632
caenorhabditis_elegans		WBGENE00003634
caenorhabditis_elegans		WBGENE00003638
caenorhabditis_elegans		WBGENE00003640
caenorhabditis_elegans		WBGENE00003641
caenorhabditis_elegans		WBGENE00003642
caenorhabditis_elegans		WBGENE00003643
caenorhabditis_elegans		WBGENE00003644
caenorhabditis_elegans		WBGENE00003645
caenorhabditis_elegans		WBGENE00003646
caenorhabditis_elegans		WBGENE00003648
caenorhabditis_elegans		WBGENE00003649
caenorhabditis_elegans		WBGENE00003651
caenorhabditis_elegans		WBGENE00003653
caenorhabditis_elegans		WBGENE00003655
caenorhabditis_elegans		WBGENE00003658
caenorhabditis_elegans		WBGENE00003660
caenorhabditis_elegans		WBGENE00003662
caenorhabditis_elegans	nhr-73	WBGENE00003663
caenorhabditis_elegans	nhr-77	WBGENE00003667
caenorhabditis_elegans		WBGENE00003669
caenorhabditis_elegans	nhr-81	WBGENE00003671
caenorhabditis_elegans	nhr-82	WBGENE00003672
caenorhabditis_elegans		WBGENE00003676
caenorhabditis_elegans		WBGENE00003677
caenorhabditis_elegans		WBGENE00003680
caenorhabditis_elegans		WBGENE00003682
caenorhabditis_elegans		WBGENE00003684
caenorhabditis_elegans		WBGENE00003685
caenorhabditis_elegans		WBGENE00003686
caenorhabditis_elegans		WBGENE00003688
caenorhabditis_elegans		WBGENE00003689
caenorhabditis_elegans		WBGENE00003692
caenorhabditis_elegans		WBGENE00003693
caenorhabditis_elegans		WBGENE00003694
caenorhabditis_elegans		WBGENE00003696
caenorhabditis_elegans		WBGENE00003698
caenorhabditis_elegans		WBGENE00003699
caenorhabditis_elegans		WBGENE00003700
caenorhabditis_elegans		WBGENE00003702
caenorhabditis_elegans		WBGENE00003704
caenorhabditis_elegans		WBGENE00003705
caenorhabditis_elegans		WBGENE00003707
caenorhabditis_elegans		WBGENE00003708
caenorhabditis_elegans		WBGENE00003712
caenorhabditis_elegans		WBGENE00003713
caenorhabditis_elegans		WBGENE00003714
caenorhabditis_elegans		WBGENE00003715
caenorhabditis_elegans		WBGENE00003716
caenorhabditis_elegans		WBGENE00003717
caenorhabditis_elegans		WBGENE00003718
caenorhabditis_elegans		WBGENE00003720
caenorhabditis_elegans		WBGENE00003721
caenorhabditis_elegans		WBGENE00003722
caenorhabditis_elegans		WBGENE00003723
caenorhabditis_elegans		WBGENE00003724
caenorhabditis_elegans		WBGENE00003725
caenorhabditis_elegans		WBGENE00003728
caenorhabditis_elegans		WBGENE00004786
caenorhabditis_elegans		WBGENE00006471
caenorhabditis_elegans	unc-55	WBGENE00006790
caenorhabditis_elegans		WBGENE00007367
caenorhabditis_elegans		WBGENE00008056
caenorhabditis_elegans	nhr-165	WBGENE00008158
caenorhabditis_elegans		WBGENE00008208
caenorhabditis_elegans	nhr-169	WBGENE00008289
caenorhabditis_elegans		WBGENE00008309
caenorhabditis_elegans	nhr-174	WBGENE00008474
caenorhabditis_elegans		WBGENE00008619
caenorhabditis_elegans		WBGENE00008630
caenorhabditis_elegans		WBGENE00008778
caenorhabditis_elegans		WBGENE00008830
caenorhabditis_elegans		WBGENE00008884
caenorhabditis_elegans		WBGENE00008901
caenorhabditis_elegans	nhr-265	WBGENE00009608
caenorhabditis_elegans		WBGENE00010017
caenorhabditis_elegans		WBGENE00010180
caenorhabditis_elegans		WBGENE00010186
caenorhabditis_elegans		WBGENE00010215
caenorhabditis_elegans		WBGENE00010410
caenorhabditis_elegans		WBGENE00010600
caenorhabditis_elegans		WBGENE00010601
caenorhabditis_elegans		WBGENE00010602
caenorhabditis_elegans		WBGENE00010603
caenorhabditis_elegans		WBGENE00010604
caenorhabditis_elegans		WBGENE00011002
caenorhabditis_elegans		WBGENE00011150
caenorhabditis_elegans		WBGENE00011396
caenorhabditis_elegans		WBGENE00011520
caenorhabditis_elegans		WBGENE00011565
caenorhabditis_elegans		WBGENE00011566
caenorhabditis_elegans		WBGENE00011568
caenorhabditis_elegans	nhr-217	WBGENE00011651
caenorhabditis_elegans		WBGENE00011750
caenorhabditis_elegans		WBGENE00012050
caenorhabditis_elegans		WBGENE00012056
caenorhabditis_elegans		WBGENE00012446
caenorhabditis_elegans		WBGENE00012449
caenorhabditis_elegans		WBGENE00012596
caenorhabditis_elegans		WBGENE00012703
caenorhabditis_elegans		WBGENE00013067
caenorhabditis_elegans		WBGENE00013483
caenorhabditis_elegans	nhr-276	WBGENE00013512
caenorhabditis_elegans		WBGENE00013584
caenorhabditis_elegans		WBGENE00013940
caenorhabditis_elegans		WBGENE00014068
caenorhabditis_elegans	nhr-245	WBGENE00014189
caenorhabditis_elegans		WBGENE00014193
caenorhabditis_elegans		WBGENE00015497
caenorhabditis_elegans		WBGENE00015758
caenorhabditis_elegans		WBGENE00015897
caenorhabditis_elegans		WBGENE00015900
caenorhabditis_elegans		WBGENE00015901
caenorhabditis_elegans		WBGENE00015902
caenorhabditis_elegans		WBGENE00016091
caenorhabditis_elegans		WBGENE00016233
caenorhabditis_elegans		WBGENE00016364
caenorhabditis_elegans		WBGENE00016365
caenorhabditis_elegans		WBGENE00016366
caenorhabditis_elegans		WBGENE00016367
caenorhabditis_elegans		WBGENE00016368
caenorhabditis_elegans		WBGENE00016517
caenorhabditis_elegans		WBGENE00016772
caenorhabditis_elegans		WBGENE00016926
caenorhabditis_elegans		WBGENE00016927
caenorhabditis_elegans		WBGENE00017503
caenorhabditis_elegans		WBGENE00017512
caenorhabditis_elegans		WBGENE00017961
caenorhabditis_elegans		WBGENE00018189
caenorhabditis_elegans		WBGENE00018265
caenorhabditis_elegans		WBGENE00018266
caenorhabditis_elegans		WBGENE00018404
caenorhabditis_elegans		WBGENE00018412
caenorhabditis_elegans		WBGENE00018415
caenorhabditis_elegans		WBGENE00018539
caenorhabditis_elegans		WBGENE00018541
caenorhabditis_elegans		WBGENE00018542
caenorhabditis_elegans		WBGENE00018544
caenorhabditis_elegans		WBGENE00018545
caenorhabditis_elegans		WBGENE00018622
caenorhabditis_elegans		WBGENE00019115
caenorhabditis_elegans		WBGENE00019116
caenorhabditis_elegans		WBGENE00019741
caenorhabditis_elegans		WBGENE00019742
caenorhabditis_elegans		WBGENE00019743
caenorhabditis_elegans		WBGENE00020015
caenorhabditis_elegans		WBGENE00020062
caenorhabditis_elegans		WBGENE00020152
caenorhabditis_elegans		WBGENE00020153
caenorhabditis_elegans		WBGENE00020385
caenorhabditis_elegans		WBGENE00020460
caenorhabditis_elegans		WBGENE00020555
caenorhabditis_elegans		WBGENE00020750
caenorhabditis_elegans		WBGENE00020849
caenorhabditis_elegans		WBGENE00020850
caenorhabditis_elegans		WBGENE00020851
caenorhabditis_elegans		WBGENE00020852
caenorhabditis_elegans		WBGENE00021163
caenorhabditis_elegans		WBGENE00021522
caenorhabditis_elegans		WBGENE00021610
caenorhabditis_elegans		WBGENE00021611
caenorhabditis_elegans		WBGENE00021617
caenorhabditis_elegans		WBGENE00022097
caenorhabditis_elegans		WBGENE00022637
caenorhabditis_elegans		WBGENE00022639
caenorhabditis_elegans		WBGENE00022640
caenorhabditis_elegans		WBGENE00022726
caenorhabditis_elegans		WBGENE00022756
caenorhabditis_elegans		WBGENE00022805
caenorhabditis_elegans		WBGENE00044353
caenorhabditis_elegans		WBGENE00044699
caenorhabditis_elegans		WBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Peroxisome proliferator-activated receptor delta — Q03181 (reviewed: Q03181)

Alternative names: NUCI, Nuclear hormone receptor 1, Nuclear receptor subfamily 1 group C member 2, Peroxisome proliferator-activated receptor beta

All UniProt accessions (2): Q03181, F1D8S7

UniProt curated annotations — full annotation on UniProt →

Function. Ligand-activated transcription factor key mediator of energy metabolism in adipose tissues. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.

Subunit / interactions. Heterodimer with the retinoid X receptor. Interacts (via domain NR LBD) with CRY1 and CRY2 in a ligand-dependent manner.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous with maximal levels in placenta and skeletal muscle.

Post-translational modifications. ‘Lys-48’-linked polyubiquitinated; leading to proteasomal degradation. Deubiquitinated and stabilized by OTUD3.

Similarity. Belongs to the nuclear hormone receptor family. NR1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q03181-1	1	yes
Q03181-2	2
Q03181-3	3
Q03181-4	4

RefSeq proteins (5): NP_001165289, NP_001165290, NP_001165291, NP_006229, NP_803184 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR003074	1Cnucl_rcpt	Family
IPR003075	1Cnucl_rcpt_B	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050234	Nuclear_hormone_rcpt_NR1	Family

Pfam: PF00104, PF00105

UniProt features (46 total): helix 17, strand 11, splice variant 4, sequence conflict 4, zinc finger region 2, turn 2, compositionally biased region 2, chain 1, domain 1, DNA-binding region 1, region of interest 1

Structure

Experimental structures (PDB)

56 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5U3Q	X-RAY DIFFRACTION	1.5
5Y7X	X-RAY DIFFRACTION	1.7
5U3T	X-RAY DIFFRACTION	1.7
5U42	X-RAY DIFFRACTION	1.7
5U3Z	X-RAY DIFFRACTION	1.72
5U3W	X-RAY DIFFRACTION	1.8
7WGN	X-RAY DIFFRACTION	1.81
5U3V	X-RAY DIFFRACTION	1.84
5U3Y	X-RAY DIFFRACTION	1.9
5U41	X-RAY DIFFRACTION	1.9
5U43	X-RAY DIFFRACTION	1.9
7VWF	X-RAY DIFFRACTION	1.9
5U3R	X-RAY DIFFRACTION	1.95
5U45	X-RAY DIFFRACTION	1.95
8ZNN	X-RAY DIFFRACTION	1.95
3TKM	X-RAY DIFFRACTION	1.95
2AWH	X-RAY DIFFRACTION	2
2B50	X-RAY DIFFRACTION	2
3GZ9	X-RAY DIFFRACTION	2
5U3S	X-RAY DIFFRACTION	2
5U40	X-RAY DIFFRACTION	2
5U46	X-RAY DIFFRACTION	2
5XMX	X-RAY DIFFRACTION	2
7WGL	X-RAY DIFFRACTION	2.09
5U3U	X-RAY DIFFRACTION	2.1
5U3X	X-RAY DIFFRACTION	2.1
5ZXI	X-RAY DIFFRACTION	2.1
6A6P	X-RAY DIFFRACTION	2.1
7VWH	X-RAY DIFFRACTION	2.1
8HF8	X-RAY DIFFRACTION	2.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03181-F1	83.65	0.68

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-200425	Carnitine shuttle
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-5362517	Signaling by Retinoic Acid

MSigDB gene sets: 476 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (71): negative regulation of transcription by RNA polymerase II (GO:0000122), glucose metabolic process (GO:0006006), proteoglycan metabolic process (GO:0006029), generation of precursor metabolites and energy (GO:0006091), regulation of transcription by RNA polymerase II (GO:0006357), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid beta-oxidation (GO:0006635), apoptotic process (GO:0006915), heart development (GO:0007507), embryo implantation (GO:0007566), cholesterol metabolic process (GO:0008203), cell population proliferation (GO:0008283), axon ensheathment (GO:0008366), phospholipid biosynthetic process (GO:0008654), fatty acid catabolic process (GO:0009062), response to glucose (GO:0009749), hormone-mediated signaling pathway (GO:0009755), positive regulation of gene expression (GO:0010628), negative regulation of cholesterol storage (GO:0010887), response to activity (GO:0014823), regulation of skeletal muscle satellite cell proliferation (GO:0014842), negative regulation of smooth muscle cell migration (GO:0014912), fatty acid transport (GO:0015908), cell differentiation (GO:0030154), negative regulation of cell growth (GO:0030308), intracellular receptor signaling pathway (GO:0030522), cell-substrate adhesion (GO:0031589), cellular response to nutrient levels (GO:0031669), negative regulation of collagen biosynthetic process (GO:0032966), response to vitamin A (GO:0033189), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), wound healing (GO:0042060), vasodilation (GO:0042311), negative regulation of apoptotic process (GO:0043066), positive regulation of skeletal muscle tissue regeneration (GO:0043415), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), keratinocyte proliferation (GO:0043616), positive regulation of fat cell differentiation (GO:0045600), negative regulation of myoblast differentiation (GO:0045662)

GO Molecular Function (17): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), lipid binding (GO:0008289), NF-kappaB binding (GO:0051059), linoleic acid binding (GO:0070539), sequence-specific double-stranded DNA binding (GO:1990837), fatty acid binding (GO:0005504), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fatty acid metabolism	1
Generic Transcription Pathway	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
hexose metabolic process	1
glycoprotein metabolic process	1
metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
animal organ development	1
circulatory system development	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
cellular process	1
ensheathment of neurons	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
response to hexose	1
signal transduction	1
cellular response to hormone stimulus	1
gene expression	1
regulation of gene expression	1

Protein interactions and networks

STRING

2832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPARD	FABP5	Q01469	978
PPARD	PPARGC1A	Q9UBK2	924
PPARD	PPARA	Q07869	887
PPARD	RXRA	P19793	839
PPARD	NCOR1	O75376	807
PPARD	CD36	P16671	787
PPARD	PPARGC1B	Q86YN6	774
PPARD	UCP3	P55916	769
PPARD	SCARB2	Q14108	764
PPARD	SCARB1	Q8WTV0	762
PPARD	CPT1B	Q92523	757
PPARD	FABP4	P15090	751
PPARD	XPR1	Q9UBH6	748
PPARD	UCP1	P25874	742
PPARD	UCP2	P55851	741

IntAct

40 interactions, top by confidence:

A	B	Type	Score
PPARD	AKT1	psi-mi:“MI:0915”(physical association)	0.550
PPARD	AKT1	psi-mi:“MI:2364”(proximity)	0.550
AKT1	PPARD	psi-mi:“MI:0915”(physical association)	0.550
PPARD	KDM1A	psi-mi:“MI:0915”(physical association)	0.510
PPARD	BRAF	psi-mi:“MI:2364”(proximity)	0.470
PPARD	BRAF	psi-mi:“MI:0915”(physical association)	0.470
NCOA1	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
PPARGC1A	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
CREBBP	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
NCOA2	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
PPARD	NCOR1	psi-mi:“MI:0407”(direct interaction)	0.440
	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
NR1H2	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
NR1H3	PPARD	psi-mi:“MI:0407”(direct interaction)	0.440
PPARD	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
SMAD9	PPARD	psi-mi:“MI:0915”(physical association)	0.370
PPARD	PRMT3	psi-mi:“MI:0915”(physical association)	0.370
PPARD	MDM4	psi-mi:“MI:0914”(association)	0.350
PPARD	ACACB	psi-mi:“MI:0914”(association)	0.350
PPARD	LRP6	psi-mi:“MI:0914”(association)	0.350
FBXW7	PPARD	psi-mi:“MI:2364”(proximity)	0.270
PPARD	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	PPARD	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (152): KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), PPARD (Reconstituted Complex), NCOR1 (Reconstituted Complex), RXRA (Affinity Capture-Western), RXRB (Affinity Capture-Western), RXRG (Affinity Capture-Western), RXRA (Reconstituted Complex), NCOA1 (Reconstituted Complex), NCOA3 (Reconstituted Complex), RXRA (Two-hybrid), PPARD (Reconstituted Complex), PPARD (Reconstituted Complex), UBB (Affinity Capture-MS), MDM2 (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z4, O00482, O35507, O42101, O76202, O95718, P03372, P06211, P11475, P19785, P22449, P28701, P28705, P35396, P35398, P37234, P41235, P45448, P48443, P49698, P49867, P49884, P51128, P51129, P51448, P54779, P57783, P70033, Q03181, Q06726, Q0GFF6, Q0VC20, Q0ZAQ8, Q15406, Q29040, Q4V8R7, Q505F1, Q5BJR8, Q5REL6, Q61539

Diamond homologs: A0P8Z4, A2T928, B3SV56, O01639, O18924, O18971, O19052, O35507, O42101, O42295, O42450, O57606, O62807, O77245, O88275, P03373, P10276, P10826, P11416, P12813, P13055, P13056, P13631, P16376, P17671, P17672, P18514, P18515, P18516, P18911, P19793, P20393, P22448, P22605, P22736, P22829, P23204, P28699, P33244, P35396

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
RXRA	up-regulates	PPARD	binding
RXRB	up-regulates	PPARD	binding
PPARD	“down-regulates quantity by repression”	HSD11B2	“transcriptional regulation”
PPARD	“up-regulates quantity by expression”	CAT	“transcriptional regulation”
PPARD	“up-regulates quantity by expression”	TXN	“transcriptional regulation”
PPARD	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
2,5-dichloro-N-(2-methyl-4-nitrophenyl)benzenesulfonamide	“down-regulates activity”	PPARD	“chemical inhibition”
“mono(2-ethylhexyl) phthalate”	“up-regulates activity”	PPARD	“chemical activation”
PPARD	“up-regulates quantity by expression”	SLC25A20	“transcriptional regulation”
“perfluorohexanesulfonic acid”	“up-regulates activity”	PPARD	“chemical activation”
“perfluorononanoic acid”	“up-regulates activity”	PPARD	“chemical activation”
“perfluorooctane-1-sulfonic acid”	“up-regulates activity”	PPARD	“chemical activation”
“perfluorodecanoic acid”	“up-regulates activity”	PPARD	“chemical activation”
“perfluorododecanoic acid”	“up-regulates activity”	PPARD	“chemical activation”
“monoisononyl phthalate”	“up-regulates activity”	PPARD	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	5	88.7×	4e-07
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	5	67.1×	8e-07
Expression of BMAL (ARNTL), CLOCK, and NPAS2	5	63.7×	8e-07
Heme signaling	5	46.8×	3e-06
Transcriptional activation of mitochondrial biogenesis	5	44.3×	3e-06
ESR-mediated signaling	6	33.5×	1e-06
Cellular response to chemical stress	5	31.0×	2e-05
PPARA activates gene expression	7	28.7×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	5	14.5×	7e-04
negative regulation of apoptotic process	6	9.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

51 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2376 predictions. Top by Δscore:

Variant	Effect	Δscore
6:35411142:G:GT	donor_gain	1.0000
6:35421815:TTCAG:T	acceptor_loss	1.0000
6:35421816:TCAG:T	acceptor_loss	1.0000
6:35421818:A:AG	acceptor_gain	1.0000
6:35421819:G:GG	acceptor_gain	1.0000
6:35421908:GCC:G	donor_gain	1.0000
6:35421927:G:GT	donor_gain	1.0000
6:35423941:T:TA	acceptor_gain	1.0000
6:35423942:GCAG:G	acceptor_loss	1.0000
6:35423943:CAGCT:C	acceptor_loss	1.0000
6:35423944:A:AG	acceptor_gain	1.0000
6:35423944:A:C	acceptor_loss	1.0000
6:35423945:G:GT	acceptor_gain	1.0000
6:35423945:GC:G	acceptor_gain	1.0000
6:35423945:GCT:G	acceptor_gain	1.0000
6:35423945:GCTA:G	acceptor_gain	1.0000
6:35423945:GCTAT:G	acceptor_gain	1.0000
6:35424145:GGCG:G	donor_gain	1.0000
6:35424146:GCG:G	donor_gain	1.0000
6:35424146:GCGG:G	donor_gain	1.0000
6:35424776:GGAG:G	donor_gain	1.0000
6:35424777:GAG:G	donor_gain	1.0000
6:35424777:GAGG:G	donor_gain	1.0000
6:35424780:G:GA	donor_loss	1.0000
6:35424780:G:GG	donor_gain	1.0000
6:35424781:T:G	donor_loss	1.0000
6:35425830:A:AG	acceptor_gain	1.0000
6:35425831:G:GA	acceptor_gain	1.0000
6:35342678:ACAG:A	donor_loss	0.9900
6:35342679:CAGGT:C	donor_loss	0.9900

AlphaMissense

2929 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:35420216:T:A	C74S	1.000
6:35420216:T:C	C74R	1.000
6:35420217:G:A	C74Y	1.000
6:35420217:G:C	C74S	1.000
6:35420218:C:G	C74W	1.000
6:35420225:T:A	C77S	1.000
6:35420225:T:C	C77R	1.000
6:35420226:G:A	C77Y	1.000
6:35420226:G:C	C77S	1.000
6:35420226:G:T	C77F	1.000
6:35420227:C:G	C77W	1.000
6:35420232:A:T	D79V	1.000
6:35420243:G:C	G83R	1.000
6:35420244:G:A	G83D	1.000
6:35420249:C:A	H85N	1.000
6:35420249:C:G	H85D	1.000
6:35420250:A:G	H85R	1.000
6:35420251:C:A	H85Q	1.000
6:35420251:C:G	H85Q	1.000
6:35420252:T:A	Y86N	1.000
6:35420252:T:C	Y86H	1.000
6:35420252:T:G	Y86D	1.000
6:35420253:A:G	Y86C	1.000
6:35420255:G:C	G87R	1.000
6:35420256:G:A	G87D	1.000
6:35420256:G:T	G87V	1.000
6:35420267:T:A	C91S	1.000
6:35420267:T:C	C91R	1.000
6:35420268:G:A	C91Y	1.000
6:35420268:G:C	C91S	1.000

dbSNP variants (sampled 300 via entrez): RS1000019728 (6:35403674 A>C), RS1000051294 (6:35361049 C>G), RS1000080536 (6:35397827 C>T), RS1000097614 (6:35350634 T>C,G), RS1000133157 (6:35398043 T>C), RS1000153848 (6:35376572 C>A), RS1000184462 (6:35341679 C>A), RS1000223218 (6:35342686 G>A,T), RS1000231918 (6:35369150 A>T), RS1000239000 (6:35382919 TTTA>T,TTTATTA), RS1000348772 (6:35422489 G>A), RS1000357102 (6:35376285 C>G), RS1000395988 (6:35383531 G>T), RS1000551706 (6:35422273 G>T), RS1000699989 (6:35390865 TA>T,TAA)

Disease associations

OMIM: gene MIM:600409 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000618_19	Response to antipsychotic treatment	5.000000e-07
GCST001263_15	Height	1.000000e-11
GCST001356_35	Gout	1.000000e-07
GCST001736_1	Cataracts in type 2 diabetes	3.000000e-06
GCST001784_41	Pulmonary function (smoking interaction)	5.000000e-07
GCST004627_29	Lymphocyte count	8.000000e-14
GCST006979_276	Heel bone mineral density	5.000000e-14
GCST008163_161	Height	7.000000e-08
GCST012226_477	Waist circumference adjusted for body mass index	1.000000e-08
GCST012227_962	Hip circumference adjusted for BMI	2.000000e-08
GCST012227_970	Hip circumference adjusted for BMI	2.000000e-29
GCST012227_971	Hip circumference adjusted for BMI	8.000000e-10
GCST012227_972	Hip circumference adjusted for BMI	2.000000e-08
GCST90000025_494	Appendicular lean mass	2.000000e-33
GCST90002402_690	Platelet count	4.000000e-20
GCST90002409_29	Childhood body mass index	4.000000e-06
GCST90011900_184	Serum alkaline phosphatase levels	1.000000e-12
GCST90020028_672	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_686	Hip circumference adjusted for BMI	6.000000e-19
GCST90020028_687	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_688	Hip circumference adjusted for BMI	2.000000e-09
GCST90020028_689	Hip circumference adjusted for BMI	6.000000e-10
GCST90020029_1542	Waist circumference adjusted for body mass index	4.000000e-11

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004587	lymphocyte count
EFO:0009270	heel bone mineral density
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004309	platelet count
EFO:0004340	body mass index
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111371 (SELECTIVITY GROUP), CHEMBL3559683 (PROTEIN FAMILY), CHEMBL3979 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 584,867 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL230158	SELADELPAR	4	854
CHEMBL247951	PEMAFIBRATE	4	604
CHEMBL295124	BERBERINE	4	26,682
CHEMBL3707395	ELAFIBRANOR	4	1,948
CHEMBL595	PIOGLITAZONE	4	57,130
CHEMBL264374	BEZAFIBRATE	3	21,822
CHEMBL4091374	LANIFIBRANOR	3	992
CHEMBL431733	NAMODENOSON	3	836
CHEMBL460026	ICOSAPENT	3	60,180
CHEMBL464982	GAMOLENIC ACID	3	26,552
CHEMBL519504	ALEGLITAZAR	3	1,072
CHEMBL107367	FARGLITAZAR	2	950
CHEMBL1232583	INDEGLITAZAR	2	274
CHEMBL181954	NAVEGLITAZAR	2	278
CHEMBL219586	GW590735	2	136
CHEMBL267476	LINOLEIC ACID	2	323,195
CHEMBL295416	PIRINIXIC ACID	2	830
CHEMBL38943	GW501516	2	1,384
CHEMBL424133	LY-518674	2	299
CHEMBL465183	DIHOMO-GAMMA-LINOLENIC ACID	2
CHEMBL8659	OLEIC ACID	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1883322	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs2016520	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs2016520	Toxicity	3	capecitabine;fluorouracil	Drug Toxicity
rs3734254	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs6922548	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms
rs7769719	Efficacy	3	docetaxel;thalidomide	Prostatic Neoplasms

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1883322	PPARD	3	2.00	1	docetaxel;thalidomide
rs2016520	PPARD	3	2.50	2	docetaxel;thalidomide;capecitabine;fluorouracil
rs3734254	PPARD	3	2.00	1	docetaxel;thalidomide
rs6922548	PPARD	3	2.00	1	docetaxel;thalidomide
rs7769719	PPARD	3	2.00	1	docetaxel;thalidomide
rs2076169	PPARD		0.00	0
rs2038067	PPARD		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 1C. Peroxisome proliferator-activated receptors

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
GW0742X	Full agonist	9.0	pIC50
GW501516	Full agonist	9.0	pEC50
L-783483	Full agonist	9.0	pKd
seladelpar	Agonist	8.72	pEC50
L-796449	Full agonist	8.7	pKi
L-165041	Full agonist	8.2	pKi
tretinoin	Full agonist	7.8	pKd
GW2433	Full agonist	6.6	pEC50
GSK0660	Antagonist	6.5	pIC50
(R)-16 [PMID: 32267688]	Agonist	6.09	pEC50
lanifibranor	Agonist	6.06	pEC50
GW9578	Full agonist	5.9	pEC50
compound 25 [PMID: 32687365]	Agonist	5.82	pEC50

Binding affinities (BindingDB)

192 measured of 229 human assays (250 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US10399958, Compound 2d	EC50	0.1 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Comparator Compound 1	EC50	0.1 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2e	EC50	0.2 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2m	EC50	0.5 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2j	EC50	0.8 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2a	EC50	1 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2h	EC50	3.5 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2c	EC50	3.7 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Comparator Compound 2	EC50	3.8 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
3-[2-ethyl-4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]phenyl]propanoic acid	EC50	4 nM	US-9346770: Compounds having activating effect on subtypes of peroxisome proliferator-activated receptors and its preparation method and uses
2-methyl-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}formamido)methyl]phenoxy}propanoic acid	EC50	4 nM
2-methyl-2-{4-[({4-methyl-2-[4-(trifluoromethoxy)phenyl]-1,3-thiazol-5-yl}formamido)methyl]phenoxy}propanoic acid	EC50	4 nM
2-methyl-2-{4-[({4-methyl-2-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}formamido)methyl]phenoxy}propanoic acid	EC50	4 nM
2-methyl-2-[4-({[4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]formamido}methyl)phenoxy]propanoic acid	EC50	4 nM
2-{(5-{[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-2-fluorophenyl)methylamino}acetic acid	EC50	4 nM
US10399958, Compound 2n	EC50	4.4 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
6-[2-[[cyclopropyl-[4-(furan-2-yl)benzoyl]amino]methyl]phenoxy]hexanoic acid	EC50	4.81 nM	US-10188627: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
2-[4-({[2-(4-tert-butylphenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	5 nM
US10399958, Compound 2k	EC50	6.6 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2b	EC50	7.8 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2o	EC50	9.9 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
2-[4-({[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	10 nM
2-[4-({[2-(4-methoxyphenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	10 nM
2-{(3-{[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}phenyl)methylamino}acetic acid	EC50	10 nM
6-[2-[[[4-(furan-2-yl)benzoyl]-methylamino]methyl]phenoxy]hexanoic acid	EC50	12.6 nM	US-10188627: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2p	EC50	13.1 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2l	EC50	13.5 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2q	EC50	14.3 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2s	EC50	18 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2i	EC50	18.8 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
US10399958, Compound 2f	EC50	24.3 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
3-[2-ethyl-4-[2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl]propanoic acid	EC50	29 nM	US-9346770: Compounds having activating effect on subtypes of peroxisome proliferator-activated receptors and its preparation method and uses
2-methyl-2-[4-({[4-methyl-2-(4-nitrophenyl)-1,3-thiazol-5-yl]formamido}methyl)phenoxy]propanoic acid	EC50	30 nM
2-methyl-2-{2-methyl-4-[({3-[4-(trifluoromethoxy)phenyl]-1,2,4-thiadiazol-5-yl}methyl)sulfanyl]phenoxy}propanoic acid	EC50	33 nM
US10399958, Compound 2g	EC50	39 nM	US-10399958: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
2-[4-({[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	40 nM
2-[(1S)-5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	43 nM
2-[(1S)-5-{3-[2-methoxy-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	44 nM
2-[(1S)-5-(3-{4-[4-(propan-2-yloxy)-1,3-thiazol-2-yl]-2-propylphenoxy}propoxy)-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	47 nM
2-[(1S)-5-[3-(4-{4H,5H,6H-cyclopenta[d][1,3]thiazol-2-yl}-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	53 nM
6-[2-[[methyl-(2-methyl-1-benzofuran-5-carbonyl)amino]methyl]phenoxy]hexanoic acid	EC50	60.2 nM	US-10188627: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
2-[(1S)-5-{3-[4-(4-ethoxy-5-methyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	61 nM
2-[4-({[3-(4-tert-butylphenyl)-1,2,4-thiadiazol-5-yl]methyl}sulfanyl)-2-methylphenoxy]-2-methylpropanoic acid	EC50	64 nM
2-methyl-2-(4-{[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]methyl}phenoxy)propanoic acid	EC50	70 nM
2-methyl-2-{2-methyl-4-[({3-[4-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-5-yl}methyl)sulfanyl]phenoxy}propanoic acid	EC50	79 nM
(E)-6-(2-((4-(furan-2-yl)-N-methylbenzamido)methyl)phenoxy)hex-2-enoic acid	EC50	80.4 nM	US-10188627: PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
2-[(1S)-5-{3-[4-(4,5-dimethyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	83 nM
2-[(1S)-5-{3-[4-(4-tert-butyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	87 nM
2-methyl-2-[2-methyl-4-({3-[4-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-5-yl}methoxy)phenoxy]propanoic acid	EC50	94 nM
2-methyl-2-[2-methyl-4-({3-[4-(trifluoromethoxy)phenyl]-1,2,4-thiadiazol-5-yl}methoxy)phenoxy]propanoic acid	EC50	94 nM

ChEMBL bioactivities

2585 potent at pChembl≥5 of 2707 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.99	Ki	0.0102	nM	CHEMBL387921
10.52	EC50	0.03	nM	CHEMBL390005
10.32	Ki	0.048	nM	GW501516
10.22	EC50	0.06	nM	CHEMBL230063
10.00	EC50	0.1	nM	CHEMBL5955597
10.00	EC50	0.1	nM	CHEMBL5931937
9.80	Ki	0.16	nM	CHEMBL200732
9.74	EC50	0.18	nM	GW501516
9.70	EC50	0.2	nM	CHEMBL4755323
9.52	EC50	0.3	nM	CHEMBL4755323
9.52	Ki	0.3	nM	CHEMBL435523
9.40	Kd	0.4	nM	CHEMBL38508
9.40	EC50	0.4	nM	CHEMBL4649683
9.40	EC50	0.4	nM	CHEMBL5417169
9.37	Ki	0.43	nM	NAMODENOSON
9.30	EC50	0.5	nM	GW501516
9.30	EC50	0.5	nM	CHEMBL5925396
9.30	EC50	0.5	nM	CHEMBL1643201
9.24	EC50	0.58	nM	CHEMBL220124
9.22	EC50	0.6	nM	GW501516
9.22	Ki	0.6	nM	CHEMBL499312
9.21	Ki	0.62	nM	CHEMBL227279
9.15	EC50	0.7	nM	CHEMBL4249571
9.15	EC50	0.7	nM	CHEMBL4635689
9.15	EC50	0.7	nM	CHEMBL4640515
9.14	EC50	0.72	nM	CHEMBL375471
9.10	EC50	0.8	nM	CHEMBL4739884
9.10	EC50	0.8	nM	CHEMBL5395441
9.10	EC50	0.8	nM	CHEMBL5936030
9.10	EC50	0.8	nM	GW501516
9.09	Ki	0.82	nM	GW501516
9.05	EC50	0.9	nM	CHEMBL1169827
9.04	EC50	0.91	nM	CHEMBL375471
9.02	EC50	0.95	nM	CHEMBL220570
9.00	EC50	1	nM	CHEMBL2035069
9.00	EC50	1	nM	CHEMBL38508
9.00	IC50	1	nM	CHEMBL38508
9.00	EC50	1	nM	GW501516
9.00	IC50	1	nM	GW501516
9.00	EC50	1	nM	CHEMBL193426
9.00	EC50	1	nM	CHEMBL3786533
9.00	EC50	1	nM	CHEMBL213315
9.00	EC50	1	nM	CHEMBL238357
9.00	EC50	1	nM	CHEMBL212911
9.00	EC50	1	nM	CHEMBL4743546
9.00	Ki	1	nM	GW501516
9.00	EC50	1	nM	CHEMBL5401474
9.00	EC50	1	nM	CHEMBL5960113
9.00	EC50	1	nM	CHEMBL1075732
9.00	EC50	1	nM	CHEMBL1080365

PubChem BioAssay actives

2612 with measured affinity, of 5997 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3R,4S)-2-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]thiolane-3,4-diol	1451024: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARdelta LBD by TR-FRET assay	ki	<0.0001	uM
2-[2-methyl-4-[(2R)-2-[[4-(trifluoromethyl)phenoxy]methyl]butyl]sulfanylphenoxy]acetic acid	290903: Agonist activity at human PPARdelta receptor by cell based transactivation assay	ec50	<0.0001	uM
(2R,3R,4S)-2-[2-chloro-6-[(3-chlorophenyl)methylamino]purin-9-yl]thiolane-3,4-diol	1451024: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARdelta LBD by TR-FRET assay	ki	<0.0001	uM
2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid	1451024: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARdelta LBD by TR-FRET assay	ki	<0.0001	uM
2-[2-methyl-4-[2-[[4-(trifluoromethyl)phenoxy]methyl]butylsulfanyl]phenoxy]acetic acid	290903: Agonist activity at human PPARdelta receptor by cell based transactivation assay	ec50	0.0001	uM
(2S,3S,4R,5R)-5-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-N-methylthiolane-2-carboxamide	1451024: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARdelta LBD by TR-FRET assay	ki	0.0002	uM
2-[3-[4-[(3-phenyl-7-propyl-1,2-benzoxazol-6-yl)oxy]butoxy]phenyl]acetic acid	156777: In vitro binding affinity towards human peroxisome proliferator activated receptor delta (PPAR delta)	ki	0.0003	uM
(E)-4-methyl-6-[2-[[5-methyl-2-[4-(trifluoromethoxy)phenyl]imidazol-1-yl]methyl]phenoxy]hex-4-enoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0003	uM
(3R)-3-methyl-6-[2-[[5-methyl-2-[4-(trifluoromethoxy)phenyl]imidazol-1-yl]methyl]phenoxy]hexanoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0004	uM
2-[4-[[2,5-dioxo-3-[4-(trifluoromethyl)phenyl]imidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990531: Agonist activity at human PPARdelta transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0004	uM
(2S,3S,4R,5R)-5-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-N-methyloxolane-2-carboxamide	1451024: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARdelta LBD by TR-FRET assay	ki	0.0004	uM
2-[4-[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1,3-thiazol-5-yl]methylsulfanyl]-2-methylphenoxy]acetic acid	731520: Binding affinity to human PPARdelta (unknown origin) by competitive TR-FRET assay	kd	0.0004	uM
2-[4-[[(3R)-3-[(2,4-dichlorophenyl)carbamoyl]-3,4-dihydro-1H-isoquinolin-2-yl]methyl]-2-methylphenoxy]acetic acid	551019: Agonist activity at Gal4-fused human PPARdelta DNA binding domain expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0005	uM
2-[(1S)-5-[3-[2-methoxy-4-(1,3-thiazol-2-yl)phenoxy]propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	1798118: PPAR FRET Assay from Article 10.1021/jm061299k: “Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.”	ec50	0.0006	uM
(2R,3R,4S)-2-[2-chloro-6-[(2-chlorophenyl)methylamino]purin-9-yl]thiolane-3,4-diol	1451024: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARdelta LBD by TR-FRET assay	ki	0.0006	uM
2-[[4-[2-(5-hydroxypent-2-ynoxy)-4-[[4-(trifluoromethyl)phenoxy]methyl]phenyl]sulfanyl-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1799042: Scintillation Proximity Assay from Article 10.1016/j.bmcl.2009.04.151: “Identification of a PPARdelta agonist with partial agonistic activity on PPARgamma.”	ki	0.0006	uM
6-[2-[[2-[4-(furan-2-yl)phenyl]-5-methylimidazol-1-yl]methyl]phenoxy]hexanoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0007	uM
(3R)-6-[2-[[2-[4-(furan-2-yl)phenyl]-5-(trifluoromethyl)imidazol-1-yl]methyl]phenoxy]-3-methylhexanoic acid	1651145: Transactivation of GAL4-fused human PPARdelta expressed in African green monkey CV1 cells by luciferase reporter gene assay	ec50	0.0007	uM
2-[2-methyl-4-[(1R)-2-phenyl-1-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]sulfanylphenoxy]acetic acid	1398471: Transactivation of human PPARdelta expressed in monkey CV-1 cells coexpressing TK-PPRE-Luc after 24 hrs by luciferase reporter gene assay	ec50	0.0007	uM
(2S)-2-[[4-butoxy-3-[[[2-fluoro-4-(trifluoromethyl)benzoyl]amino]methyl]phenyl]methyl]butanoic acid	469028: Agonist activity at PPARdelta receptor expressed in HEK293 cells co-transfected with GAL4 by transactivation assay	ec50	0.0007	uM
(3R)-6-[2-[[2-(4-chloro-3-fluorophenyl)-5-methylimidazol-1-yl]methyl]phenoxy]-3-methylhexanoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0008	uM
2-[4-[[3-[3-fluoro-4-(trifluoromethyl)phenyl]-2,5-dioxoimidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990531: Agonist activity at human PPARdelta transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0008	uM
2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylselanyl]phenoxy]acetic acid	547900: Agonist activity at human PPAR-delta expressed in african green monkey CV-1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0009	uM
2-[(1S)-5-[3-[4-[5-(trifluoromethyl)-2-pyridinyl]phenoxy]propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	1798118: PPAR FRET Assay from Article 10.1021/jm061299k: “Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.”	ec50	0.0009	uM
3-[4-[(3R)-3-(2-benzoyl-4-ethylphenoxy)butoxy]-2-methylphenyl]propanoic acid	305544: Agonist activity at human Gal4-PPARdelta expressed in CV1 cells by transactivation assay	ec50	0.0010	uM
(E)-6-[2-[[2-[4-(furan-2-yl)phenyl]-5-methylimidazol-1-yl]methyl]phenoxy]-4-methylhex-4-enoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0010	uM
2-[4-[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-2-methylphenoxy]acetic acid	1291848: Agonist activity at PPAR delta (unknown origin) transfected in HEK293 cells after 24 hrs by dual-luciferase reporter gene assay	ec50	0.0010	uM
3-[2-methyl-4-[(3R)-3-[2-phenoxy-4-(trifluoromethyl)phenoxy]butoxy]phenyl]propanoic acid	270630: Transactivation of human PPARdelta in CV1 cells by luciferase reporter gene assay	ec50	0.0010	uM
2-[2-methyl-4-[[4-(2-propan-2-yloxypyrimidin-5-yl)-5-[4-(trifluoromethoxy)phenyl]-1,3-oxazol-2-yl]methoxy]phenoxy]acetic acid	469785: Agonist activity at human PPARdelta ligand binding domain expressed in human 293T cells co-transfected with Gal4-DBD by luciferase transactivation assay	ec50	0.0010	uM
2-[2,6-dimethyl-4-[[3-[3-methyl-4-(trifluoromethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]methyl]phenoxy]-2-methylpropanoic acid	1990531: Agonist activity at human PPARdelta transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0010	uM
3-[4-[3-[(1R)-1-[(5-chloro-1,3-dimethylindole-2-carbonyl)amino]ethyl]-5-fluorophenoxy]-2-ethylphenyl]propanoic acid	304336: Agonist activity at human PPARdelta expressed in CV1 cells by receptor transactivation assay	ec50	0.0010	uM
N-[(2,2-dimethylchromen-8-yl)methyl]-4-phenyl-N-propan-2-ylbenzamide	254616: Effective concentration against PPAR delta receptor	ec50	0.0010	uM
2-[2-methyl-4-[[4-(2-morpholin-4-ylpyrimidin-5-yl)-5-[4-(trifluoromethoxy)phenyl]-1,3-oxazol-2-yl]methoxy]phenoxy]acetic acid	469785: Agonist activity at human PPARdelta ligand binding domain expressed in human 293T cells co-transfected with Gal4-DBD by luciferase transactivation assay	ec50	0.0010	uM
2-[2-methyl-4-[[4-[4-[methyl(propan-2-yl)carbamoyl]phenyl]-5-[4-(trifluoromethoxy)phenyl]-1,3-oxazol-2-yl]methoxy]phenoxy]acetic acid	469785: Agonist activity at human PPARdelta ligand binding domain expressed in human 293T cells co-transfected with Gal4-DBD by luciferase transactivation assay	ec50	0.0010	uM
2-[4-[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1,3-thiazol-5-yl]methylselanyl]-2-methylphenoxy]acetic acid	547900: Agonist activity at human PPAR-delta expressed in african green monkey CV-1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0010	uM
2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]butylsulfanyl]phenoxy]acetic acid	663629: Transactivation activity at human PPARdelta expressed in african green monkey CV1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0010	uM
2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid	1291855: Agonist activity at human PPAR delta by cell based reporter assay	ec50	0.0011	uM
2-[2-methyl-4-[3-methyl-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]butyl]sulfanylphenoxy]acetic acid	663629: Transactivation activity at human PPARdelta expressed in african green monkey CV1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0011	uM
2-[4-[2-cyclopropyl-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethyl]sulfanyl-2-methylphenoxy]acetic acid	663629: Transactivation activity at human PPARdelta expressed in african green monkey CV1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0011	uM
(E)-6-[2-[[3-[4-(furan-2-yl)phenyl]-5-methyl-1H-pyrazol-4-yl]methyl]phenoxy]-4-methylhex-4-enoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0012	uM
2-[(1S)-5-[3-[4-(4-ethoxy-1,3-thiazol-2-yl)phenoxy]propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	1798118: PPAR FRET Assay from Article 10.1021/jm061299k: “Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.”	ec50	0.0012	uM
4-chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide	1266297: Binding affinity to GST-PPAR-beta/delta LBP (unknown origin) after 24 hrs by TR-FRET assay	ic50	0.0012	uM
2-[4-[2-(2-chloro-6-fluorophenyl)-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethyl]sulfanyl-2-methylphenoxy]acetic acid	663629: Transactivation activity at human PPARdelta expressed in african green monkey CV1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0012	uM
2-[4-[2-[2-fluoro-6-(trifluoromethyl)phenyl]-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethyl]sulfanyl-2-methylphenoxy]acetic acid	663629: Transactivation activity at human PPARdelta expressed in african green monkey CV1 cells after 24 hrs by luciferase reporter gene assay	ec50	0.0012	uM
2-[(1S)-5-[3-[4-(4-methoxy-1,3-thiazol-2-yl)phenoxy]propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	1798118: PPAR FRET Assay from Article 10.1021/jm061299k: “Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.”	ec50	0.0013	uM
2-[(1S)-5-[3-[4-(5,6-dihydro-4H-cyclopenta[d][1,3]thiazol-2-yl)phenoxy]propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	1798118: PPAR FRET Assay from Article 10.1021/jm061299k: “Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.”	ec50	0.0013	uM
2-[(1S)-5-[3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-methoxyphenoxy]propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	1798118: PPAR FRET Assay from Article 10.1021/jm061299k: “Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.”	ec50	0.0013	uM
(E)-6-[2-[[5-[4-(furan-2-yl)phenyl]-3-methylimidazol-4-yl]methyl]phenoxy]-4-methylhex-4-enoic acid	1716510: Modulator activity at GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay	ec50	0.0013	uM
2-methyl-2-[2-methyl-4-[[5-oxo-4-[4-(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]methyl]-6-(trifluoromethyl)phenoxy]propanoic acid	1822056: Agonist activity at PPARdelta (unknown origin)	ec50	0.0014	uM
(3R)-6-[2-[[5-chloro-2-[4-(trifluoromethyl)phenyl]imidazol-1-yl]methyl]phenoxy]-3-methylhexanoic acid	1651145: Transactivation of GAL4-fused human PPARdelta expressed in African green monkey CV1 cells by luciferase reporter gene assay	ec50	0.0015	uM

CTD chemical–gene interactions

150 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GW 501516	affects cotreatment, increases expression, affects binding, increases activity, increases reaction (+1 more)	10
(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid	affects cotreatment, decreases reaction, increases reaction, increases phosphorylation, affects binding (+2 more)	9
sulindac sulfide	affects binding, decreases activity, affects reaction, decreases expression, decreases reaction (+1 more)	6
4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid	affects binding, increases activity, increases phosphorylation, increases reaction	6
Bezafibrate	affects binding, increases activity, increases expression, increases reaction	6
Indomethacin	decreases activity, decreases expression, increases expression, affects reaction, decreases reaction	6
perfluorooctanoic acid	decreases expression, increases activity, decreases reaction, increases expression, decreases activity	5
pirinixic acid	increases expression, affects binding, increases activity, affects cotreatment	4
bisphenol A	affects binding, increases activity, decreases methylation, increases expression	4
bisphenol AF	increases expression, decreases expression, increases activity	3
Rosiglitazone	affects cotreatment, decreases reaction, increases expression, affects binding	3
Resveratrol	increases expression, decreases expression	3
Pioglitazone	affects binding, increases activity, increases expression	3
Acetaminophen	increases expression	3
Dexamethasone	decreases expression, increases expression, affects cotreatment, decreases reaction	3
Doxorubicin	decreases expression, decreases activity	3
Valproic Acid	affects binding, increases activity, increases expression, increases methylation	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Palmitic Acid	decreases expression, affects cotreatment, increases expression, affects expression	3
Linoleic Acid	increases expression, decreases expression, increases activity	3
sodium arsenite	increases expression	2
2-bromopalmitate	increases activity	2
perfluoro-n-nonanoic acid	decreases expression, increases expression	2
perfluorohexanesulfonic acid	decreases expression, increases expression	2
bisphenol S	affects binding, increases activity, increases expression	2
Aspirin	decreases activity, decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cadmium	affects response to substance, decreases expression, increases abundance, decreases activity, increases expression (+2 more)	2
Calcitriol	affects cotreatment, increases expression, increases reaction	2
Docosahexaenoic Acids	increases expression, increases reaction	2

ChEMBL screening assays

750 unique, capped per target: 573 binding, 175 functional, 1 unclassified, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1173894	Binding	Activation of PPARbeta/gamma in human HaCaT cells assessed as induction of ANGPTL4 expression by PCR	Synthesis of isosteric selenium analog of the PPARbeta/delta agonist GW501516 and comparison of biological activity. — Bioorg Med Chem Lett
CHEMBL4721897	Unclassified	Selectivity index, ratio of EC50 for transactivation of GAL4-fused PPARgamma LBD (unknown origin) transfected in African green monkey CV1 cells to EC50 for transactivation of GAL4-fused human PPARdelta LBD (128 to residue at C-terminus) tra	Selective PPARδ Modulators Improve Mitochondrial Function: Potential Treatment for Duchenne Muscular Dystrophy (DMD). — ACS Med Chem Lett
CHEMBL1001155	Functional	Agonist activity at human PPARdelta by Gal4 chimera cell-based reporter assay	Discovery of a novel class of PPARdelta partial agonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

12 cell lines: 6 cancer cell line, 3 embryonic stem cell, 2 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5N7	SEES3-1V human PPARD, clone1	Embryonic stem cell	Male
CVCL_A5N8	SEES3-1V human PPARD, clone2	Embryonic stem cell	Male
CVCL_A5N9	SEES3-1V human PPARD, clone3	Embryonic stem cell	Male
CVCL_B8MW	Abcam HCT 116 PPARD KO	Cancer cell line	Male
CVCL_B9Q5	Abcam A-549 PPARD KO	Cancer cell line	Male
CVCL_D2H1	Abcam MCF-7 PPARD KO	Cancer cell line	Female
CVCL_D9P2	Ubigene HEK293 PPARD KO	Transformed cell line	Female
CVCL_HD88	HCT 116 PPARD(-/-)	Cancer cell line	Male
CVCL_KY80	PathHunter CHO-K1 PPARdelta Protein Interaction	Spontaneously immortalized cell line	Female
CVCL_LF41	GeneBLAzer PPARdelta-UAS-bla HEK 293T	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.