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Atlas / Gene / NR1H3

NR1H3

gene
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Also known as LXR-aRLD-1LXRa

Summary

NR1H3 (nuclear receptor subfamily 1 group H member 3, HGNC:7966) is a protein-coding gene on chromosome 11p11.2, encoding Oxysterols receptor LXR-alpha (Q13133). Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity.

The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10062 — RefSeq curated summary.

At a glance

  • GWAS associations: 19
  • Clinical variants (ClinVar): 77 total — 1 pathogenic
  • Druggable target: yes — 12 molecules with ChEMBL bioactivity
  • Transcription factor: yes — 146 downstream targets (CollecTRI)
  • MANE Select transcript: NM_005693

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7966
Approved symbolNR1H3
Namenuclear receptor subfamily 1 group H member 3
Location11p11.2
Locus typegene with protein product
StatusApproved
AliasesLXR-a, RLD-1, LXRa
Ensembl geneENSG00000025434
Ensembl biotypeprotein_coding
OMIM602423
Entrez10062

Gene structure

Transcript identifiers

Ensembl transcripts: 78 — 60 protein_coding, 9 protein_coding_CDS_not_defined, 7 retained_intron, 2 nonsense_mediated_decay

ENST00000395397, ENST00000405576, ENST00000405853, ENST00000407404, ENST00000412937, ENST00000419652, ENST00000420369, ENST00000436029, ENST00000436778, ENST00000437276, ENST00000441012, ENST00000444396, ENST00000449369, ENST00000457932, ENST00000461778, ENST00000462051, ENST00000467728, ENST00000473222, ENST00000476086, ENST00000481020, ENST00000481889, ENST00000483882, ENST00000486991, ENST00000487913, ENST00000494018, ENST00000495866, ENST00000498548, ENST00000525441, ENST00000527464, ENST00000527949, ENST00000529540, ENST00000530310, ENST00000531660, ENST00000532630, ENST00000616973, ENST00000896726, ENST00000896727, ENST00000896728, ENST00000896729, ENST00000896730, ENST00000896731, ENST00000896732, ENST00000896733, ENST00000896734, ENST00000896735, ENST00000896736, ENST00000896737, ENST00000896738, ENST00000896739, ENST00000896740, ENST00000896741, ENST00000896742, ENST00000896743, ENST00000896744, ENST00000896745, ENST00000896746, ENST00000896747, ENST00000896748, ENST00000896749, ENST00000896750, ENST00000896751, ENST00000896752, ENST00000896753, ENST00000896754, ENST00000896757, ENST00000896759, ENST00000932404, ENST00000932405, ENST00000932406, ENST00000932407, ENST00000965455, ENST00000965456, ENST00000965457, ENST00000965458, ENST00000965459, ENST00000965460, ENST00000965461, ENST00000965462

RefSeq mRNA: 6 — MANE Select: NM_005693 NM_001130101, NM_001130102, NM_001251934, NM_001251935, NM_001363595, NM_005693

CCDS: CCDS44584, CCDS44585, CCDS73285, CCDS7929, CCDS86200

Canonical transcript exons

ENST00000441012 — 10 exons

ExonStartEnd
ENSE000015636494725799647258129
ENSE000021877064726855047269033
ENSE000034663424726826147268355
ENSE000035202734726124147261449
ENSE000035457514726154747261726
ENSE000035490074726191947262018
ENSE000035497044726040947260675
ENSE000036175794725918047259259
ENSE000036547634726791347268026
ENSE000037860504725979147259979

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 97.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.1958 / max 1482.0936, expressed in 1679 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter IDTPM avgSamples expressed
11417626.5966969
1141711.7695944
1141720.8343477
1141740.7559401
1141770.6433141
1141750.4842199
1141730.077433
1141780.034517

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111497.60gold quality
omental fat padUBERON:001041496.72gold quality
peritoneumUBERON:000235896.63gold quality
adipose tissue of abdominal regionUBERON:000780896.32gold quality
mucosa of transverse colonUBERON:000499196.27gold quality
spleenUBERON:000210695.93gold quality
tibial nerveUBERON:000132395.91gold quality
subcutaneous adipose tissueUBERON:000219095.05gold quality
adipose tissueUBERON:000101393.78gold quality
small intestine Peyer’s patchUBERON:000345493.75gold quality
endocervixUBERON:000045893.31gold quality
transverse colonUBERON:000115793.19gold quality
liverUBERON:000210792.75gold quality
small intestineUBERON:000210892.61gold quality
connective tissueUBERON:000238492.61gold quality
gall bladderUBERON:000211092.56gold quality
lymph nodeUBERON:000002992.40gold quality
right lobe of thyroid glandUBERON:000111992.37gold quality
right adrenal gland cortexUBERON:003582792.20gold quality
right adrenal glandUBERON:000123391.80gold quality
apex of heartUBERON:000209891.72gold quality
left testisUBERON:000453391.53gold quality
mucosa of stomachUBERON:000119991.48gold quality
right testisUBERON:000453491.46gold quality
right uterine tubeUBERON:000130291.43gold quality
left lobe of thyroid glandUBERON:000112091.41gold quality
left uterine tubeUBERON:000130391.29gold quality
right ovaryUBERON:000211891.27gold quality
left adrenal glandUBERON:000123491.15gold quality
left adrenal gland cortexUBERON:003582591.08gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

146 targets.

TargetRegulation
ABCA1Activation
ABCA12Unknown
ABCC2Activation
ABCD2Repression
ABCG1Activation
ABCG4Activation
ABCG5Activation
ABCG8Activation
ABL2
ACACA
ACSL3Activation
ADAM2
AGTR1
AHRUnknown
AKR1C4
ANGPTL3
AP1
APOA1Activation
APOA2Unknown
APOA5Unknown
APOC2
APOEActivation
APRT
ARG1
ARL4CUnknown
BARD1
BHLHE40Activation
C3Activation
C7
CCL2

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CREBZF, ESR1, FOXC1, GLI2, HES1, NFIA, NR0B1, NR0B2, NR1H2, NR1H3, NR1H4, NR3C1, PPARA, PPARG, RORA, RXRA, SREBF2, THRB, VDR

miRNA regulators (miRDB)

19 targeting NR1H3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-453199.9969.703181
HSA-MIR-570-3P99.9672.414910
HSA-MIR-61399.9171.501710
HSA-MIR-4668-5P99.7970.583782
HSA-MIR-451699.6167.783390
HSA-MIR-361299.4566.021333
HSA-MIR-65099.4565.771309
HSA-MIR-130A-5P99.3370.262623
HSA-MIR-449B-3P99.2067.241047
HSA-MIR-4795-5P99.1166.90876
HSA-MIR-62298.9966.481050
HSA-MIR-6840-3P98.6865.951923
HSA-MIR-1227-5P98.6565.321549
HSA-MIR-6880-5P98.0865.591282
HSA-MIR-4797-3P97.4867.14989
HSA-MIR-6886-3P96.9666.36844
HSA-MIR-4436B-5P96.7168.371346
HSA-MIR-452295.7666.23742
HSA-MIR-6796-5P95.3766.081120

Literature-anchored findings (GeneRIF, showing 40)

  • data suggest a model in which LXR ligands trigger an autoregulatory loop leading to selective induction of hLXRalpha gene expression (PMID:11875109)
  • studies demonstrate that activated LXR induces the expression of the apoE/C-I/C-IV/C-II gene cluster in both human and murine macrophages (PMID:12032151)
  • Different regulation of the LXRalpha promoter activity by isoforms of CCAAT/enhancer-binding proteins (PMID:12054659)
  • interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter (PMID:12117567)
  • LXRa is regulated by fatty acids in human cells (PMID:12161442)
  • SHP is able to interact with LXR and to modulate its transcriptional activity. (PMID:12198243)
  • PGC-1 alpha serves as a co-activator for the liver X receptor (LXR) alpha (PMID:12470296)
  • These data enable the identification of the amino acids that coordinate the interaction of both steroidal and non-steroidal ligands in the ligand-binding pocket of liver X receptor alpha. (PMID:12932788)
  • hLXRalpha and hLXRgeta transactivated a reporter gene bearing a truncated FPPS promoter containing a putative direct repeat 4 (DR4) LXR response element, and direct interaction was demonstrated (PMID:12957674)
  • LXRalpha and LXRbeta regulate transcription of the vascular endothelial growth factor gene in macrophages (PMID:14699103)
  • unliganded TRbeta1 suppresses promoter activity driven by LXRalpha and its ligand, whereas transactivation by T3-bound TRbeta1 is not affected by LXRalpha in the presence or absence of oxysterols (PMID:15319359)
  • LXRalpha plays an important role in the cAMP-mediated regulation of human renin gene transcription by binding to cAMP responsive element in the promoter. (PMID:15353176)
  • LXRs are expressed and functional in primary human coronary artery smooth muscle cells; their ligands inhibit cell proliferation and neointima formation (PMID:15539633)
  • activation of the liver X receptors (LXR) dramatically promoted lipid accumulation in vascular smooth muscle cells (PMID:15548517)
  • In the human body, the LXRalpha protein is highly expressed in macrophage lineage cells and foam cells in atherosclerotic lesions (PMID:15625283)
  • The beneficial effect of hepatic LXRalpha was abrogated by a synthetic LXR agonist, which activated SREBP-1c and its target genes. (PMID:16054077)
  • liver X receptor-alpha in mouse kidney and HK-2 proximal tubular cells is downregulated by LPS and cytokines (PMID:16106051)
  • expression of alternative LXRalpha transcripts in certain biological contexts may impact LXR signaling and lipid metabolism (PMID:16170053)
  • LXRalpha is a negative modulator of Abcd2, acting through a novel regulatory mechanism involving overlapping SREBP and LXRalpha binding sites (PMID:16249184)
  • competitive binding of coactivators and corepressors can explain the tissue-specific behavior of partial liver X receptor alpha and beta agonists (PMID:16354658)
  • LXR agonists may lead to increased utilisation of lipids and glucose in muscle cells without affecting the mechanism of action of insulin. (PMID:16482468)
  • Data demonstrate that LXR-alpha activation altered all of the cellular cholesterol fluxes. (PMID:16567856)
  • LXR-alpha gene plays a crucial role in the regulation of innate immunity at the genomic level. (PMID:16758300)
  • Results provide evidence that liver X receptors alpha and beta are phosphorylated proteins. (PMID:16904112)
  • Data show that liver X receptor alpha regulates the low-density lipoprotein receptor gene, which mediates the endocytic uptake of LDL cholesterol in the liver. (PMID:16920108)
  • in the investigated German sample, no evidence of association of ABCB11 and LXRA to gallstone susceptibility was detected. The gallstone trait is not allelic to progressive familial cholestasis at the ABCB11 locus. (PMID:16941683)
  • myeloperoxidase is regulated by LXR and PPARalpha ligands (PMID:16956579)
  • LXR-alpha and LXR-beta independently interfere with the hypothalamic-pituitary-adrenal axis regulation at the level of the pituitary and the adrenal gland (PMID:16973760)
  • One LXRA single nucleotide polymorphism, rs2279238, and one common haplotype, CAAGCC, as well as two LXRB single nucleotide polymorphisms, LB44732G>A and rs2695121, were associated with obesity phenotypes. (PMID:17108812)
  • novel mechanism of inflammatory gene regulation (C-reactive protein) by LXR ligands (PMID:17110595)
  • ROS and NF-kappaB, but not LXR, mediate the IL-1beta-induced downregulation of ABCA1 via a novel transcriptional mechanism, which might play an important role of proinflammation in the alteration of lipid metabolism. (PMID:17135302)
  • These studies define parallel but functionally distinct pathways that are utilized by PPARgamma and LXRs to differentially regulate complex programs of gene expression that control immunity and homeostasis. (PMID:17218271)
  • LXR is a potent modulator of dendritic cells maturation and function mediated in part by blocking the expression of fascin. (PMID:17255360)
  • LXRalpha is regulated not only by oxysterol derivatives but also by PKA-mediated phosphorylation, which suggests that nutritional regulation of SREBP-1c and lipogenesis could be regulated at least partially through modulation of LXR (PMID:17296605)
  • Results suggest that co-repression of LXR activity by RIP140 involves an atypical binding mode of RIP140 and a repression element in the RIP140 C-terminus. (PMID:17391100)
  • These data indicate for the first time that human macrophage aP2 promoter is a direct target for the regulation by LXR/RXR heterodimers. (PMID:17396233)
  • We show here that primary hASM cells express liver X receptor (LXR; alpha and beta subtypes), an oxysterol-activated nuclear receptor that controls expression of genes involved in lipid and cholesterol homeostasis, and inflammation. (PMID:17405904)
  • The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells. (PMID:17416342)
  • Haplotype 2 associated with reduced mortality from infectious disease. Haplotype 2 also associated with higher levels of plasma apolipoprotein E, a target gene of the LXRalpha (p =.018), and higher levels of triglycerides (p =.041). (PMID:17452725)
  • This novel insight that thyroid hormone regulates LXR-alpha mRNA levels and promoter activity should shed light on a cross talk between LXR-alpha and TR-beta1 as a new therapeutic target against dyslipidemia and atherosclerosis. (PMID:17628006)

Cross-species orthologs

188 orthologs

OrganismSymbolGene ID
danio_rerionr1h3ENSDARG00000098439
mus_musculusNr1h3ENSMUSG00000002108
rattus_norvegicusNr1h3ENSRNOG00000013172
drosophila_melanogasterEcRFBGN0000546
drosophila_melanogasterHr96FBGN0015240
caenorhabditis_elegansWBGENE00001062
caenorhabditis_elegansnhr-2WBGENE00003601
caenorhabditis_elegansWBGENE00003608
caenorhabditis_elegansWBGENE00003611
caenorhabditis_elegansWBGENE00003614
caenorhabditis_elegansWBGENE00003615
caenorhabditis_elegansWBGENE00003617
caenorhabditis_elegansWBGENE00003618
caenorhabditis_elegansWBGENE00003620
caenorhabditis_elegansnhr-23WBGENE00003622
caenorhabditis_elegansWBGENE00003624
caenorhabditis_elegansWBGENE00003632
caenorhabditis_elegansWBGENE00003634
caenorhabditis_elegansWBGENE00003638
caenorhabditis_elegansWBGENE00003640
caenorhabditis_elegansWBGENE00003641
caenorhabditis_elegansWBGENE00003642
caenorhabditis_elegansWBGENE00003643
caenorhabditis_elegansWBGENE00003644
caenorhabditis_elegansWBGENE00003645
caenorhabditis_elegansWBGENE00003646
caenorhabditis_elegansWBGENE00003648
caenorhabditis_elegansWBGENE00003649
caenorhabditis_elegansWBGENE00003651
caenorhabditis_elegansWBGENE00003653
caenorhabditis_elegansWBGENE00003655
caenorhabditis_elegansWBGENE00003658
caenorhabditis_elegansWBGENE00003660
caenorhabditis_elegansWBGENE00003662
caenorhabditis_elegansnhr-73WBGENE00003663
caenorhabditis_elegansnhr-77WBGENE00003667
caenorhabditis_elegansWBGENE00003669
caenorhabditis_elegansnhr-81WBGENE00003671
caenorhabditis_elegansnhr-82WBGENE00003672
caenorhabditis_elegansWBGENE00003676
caenorhabditis_elegansWBGENE00003677
caenorhabditis_elegansWBGENE00003680
caenorhabditis_elegansWBGENE00003682
caenorhabditis_elegansWBGENE00003684
caenorhabditis_elegansWBGENE00003685
caenorhabditis_elegansWBGENE00003686
caenorhabditis_elegansWBGENE00003688
caenorhabditis_elegansWBGENE00003689
caenorhabditis_elegansWBGENE00003692
caenorhabditis_elegansWBGENE00003693
caenorhabditis_elegansWBGENE00003694
caenorhabditis_elegansWBGENE00003696
caenorhabditis_elegansWBGENE00003698
caenorhabditis_elegansWBGENE00003699
caenorhabditis_elegansWBGENE00003700
caenorhabditis_elegansWBGENE00003702
caenorhabditis_elegansWBGENE00003704
caenorhabditis_elegansWBGENE00003705
caenorhabditis_elegansWBGENE00003707
caenorhabditis_elegansWBGENE00003708
caenorhabditis_elegansWBGENE00003712
caenorhabditis_elegansWBGENE00003713
caenorhabditis_elegansWBGENE00003714
caenorhabditis_elegansWBGENE00003715
caenorhabditis_elegansWBGENE00003716
caenorhabditis_elegansWBGENE00003717
caenorhabditis_elegansWBGENE00003718
caenorhabditis_elegansWBGENE00003720
caenorhabditis_elegansWBGENE00003721
caenorhabditis_elegansWBGENE00003722
caenorhabditis_elegansWBGENE00003723
caenorhabditis_elegansWBGENE00003724
caenorhabditis_elegansWBGENE00003725
caenorhabditis_elegansWBGENE00003728
caenorhabditis_elegansWBGENE00004786
caenorhabditis_elegansWBGENE00006471
caenorhabditis_elegansunc-55WBGENE00006790
caenorhabditis_elegansWBGENE00007367
caenorhabditis_elegansWBGENE00008056
caenorhabditis_elegansnhr-165WBGENE00008158
caenorhabditis_elegansWBGENE00008208
caenorhabditis_elegansnhr-169WBGENE00008289
caenorhabditis_elegansWBGENE00008309
caenorhabditis_elegansnhr-174WBGENE00008474
caenorhabditis_elegansWBGENE00008619
caenorhabditis_elegansWBGENE00008630
caenorhabditis_elegansWBGENE00008778
caenorhabditis_elegansWBGENE00008830
caenorhabditis_elegansWBGENE00008884
caenorhabditis_elegansWBGENE00008901
caenorhabditis_elegansnhr-265WBGENE00009608
caenorhabditis_elegansWBGENE00010017
caenorhabditis_elegansWBGENE00010180
caenorhabditis_elegansWBGENE00010186
caenorhabditis_elegansWBGENE00010215
caenorhabditis_elegansWBGENE00010410
caenorhabditis_elegansWBGENE00010600
caenorhabditis_elegansWBGENE00010601
caenorhabditis_elegansWBGENE00010602
caenorhabditis_elegansWBGENE00010603
caenorhabditis_elegansWBGENE00010604
caenorhabditis_elegansWBGENE00011002
caenorhabditis_elegansWBGENE00011150
caenorhabditis_elegansWBGENE00011396
caenorhabditis_elegansWBGENE00011520
caenorhabditis_elegansWBGENE00011565
caenorhabditis_elegansWBGENE00011566
caenorhabditis_elegansWBGENE00011568
caenorhabditis_elegansnhr-217WBGENE00011651
caenorhabditis_elegansWBGENE00011750
caenorhabditis_elegansWBGENE00012050
caenorhabditis_elegansWBGENE00012056
caenorhabditis_elegansWBGENE00012446
caenorhabditis_elegansWBGENE00012449
caenorhabditis_elegansWBGENE00012596
caenorhabditis_elegansWBGENE00012703
caenorhabditis_elegansWBGENE00013067
caenorhabditis_elegansWBGENE00013483
caenorhabditis_elegansnhr-276WBGENE00013512
caenorhabditis_elegansWBGENE00013584
caenorhabditis_elegansWBGENE00013940
caenorhabditis_elegansWBGENE00014068
caenorhabditis_elegansnhr-245WBGENE00014189
caenorhabditis_elegansWBGENE00014193
caenorhabditis_elegansWBGENE00015497
caenorhabditis_elegansWBGENE00015758
caenorhabditis_elegansWBGENE00015897
caenorhabditis_elegansWBGENE00015900
caenorhabditis_elegansWBGENE00015901
caenorhabditis_elegansWBGENE00015902
caenorhabditis_elegansWBGENE00016091
caenorhabditis_elegansWBGENE00016233
caenorhabditis_elegansWBGENE00016364
caenorhabditis_elegansWBGENE00016365
caenorhabditis_elegansWBGENE00016366
caenorhabditis_elegansWBGENE00016367
caenorhabditis_elegansWBGENE00016368
caenorhabditis_elegansWBGENE00016517
caenorhabditis_elegansWBGENE00016772
caenorhabditis_elegansWBGENE00016926
caenorhabditis_elegansWBGENE00016927
caenorhabditis_elegansWBGENE00017503
caenorhabditis_elegansWBGENE00017512
caenorhabditis_elegansWBGENE00017961
caenorhabditis_elegansWBGENE00018189
caenorhabditis_elegansWBGENE00018265
caenorhabditis_elegansWBGENE00018266
caenorhabditis_elegansWBGENE00018404
caenorhabditis_elegansWBGENE00018412
caenorhabditis_elegansWBGENE00018415
caenorhabditis_elegansWBGENE00018539
caenorhabditis_elegansWBGENE00018541
caenorhabditis_elegansWBGENE00018542
caenorhabditis_elegansWBGENE00018544
caenorhabditis_elegansWBGENE00018545
caenorhabditis_elegansWBGENE00018622
caenorhabditis_elegansWBGENE00019115
caenorhabditis_elegansWBGENE00019116
caenorhabditis_elegansWBGENE00019741
caenorhabditis_elegansWBGENE00019742
caenorhabditis_elegansWBGENE00019743
caenorhabditis_elegansWBGENE00020015
caenorhabditis_elegansWBGENE00020062
caenorhabditis_elegansWBGENE00020152
caenorhabditis_elegansWBGENE00020153
caenorhabditis_elegansWBGENE00020385
caenorhabditis_elegansWBGENE00020460
caenorhabditis_elegansWBGENE00020555
caenorhabditis_elegansWBGENE00020750
caenorhabditis_elegansWBGENE00020849
caenorhabditis_elegansWBGENE00020850
caenorhabditis_elegansWBGENE00020851
caenorhabditis_elegansWBGENE00020852
caenorhabditis_elegansWBGENE00021163
caenorhabditis_elegansWBGENE00021522
caenorhabditis_elegansWBGENE00021610
caenorhabditis_elegansWBGENE00021611
caenorhabditis_elegansWBGENE00021617
caenorhabditis_elegansWBGENE00022097
caenorhabditis_elegansWBGENE00022637
caenorhabditis_elegansWBGENE00022639
caenorhabditis_elegansWBGENE00022640
caenorhabditis_elegansWBGENE00022726
caenorhabditis_elegansWBGENE00022756
caenorhabditis_elegansWBGENE00022805
caenorhabditis_elegansWBGENE00044353
caenorhabditis_elegansWBGENE00044699
caenorhabditis_elegansWBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), 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

Oxysterols receptor LXR-alpha — Q13133 (reviewed: Q13133)

Alternative names: Liver X receptor alpha, Nuclear receptor subfamily 1 group H member 3

All UniProt accessions (16): Q13133, B4DXU5, B5MBY7, C9J2C8, C9J4R0, C9JBS2, C9JCS0, C9JEC2, C9JJ16, C9JTS4, E9PID2, E9PLL4, E9PPA1, F1D8N1, F8WC63, F8WEY6

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis. Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles. Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators.

Subunit / interactions. Heterodimer of NR1H3 and RXR (retinoic acid receptor). Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with SIRT1 and this interaction is inhibited by CCAR2. Interacts with GPS2.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Visceral organs specific expression. Strong expression was found in liver, kidney and intestine followed by spleen and to a lesser extent the adrenals.

Post-translational modifications. Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound NR1H3 when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation.

Induction. By 9-cis retinoic acid (9CRA).

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

Isoforms (3)

UniProt IDNamesCanonical?
Q13133-11yes
Q13133-22
Q13133-33

RefSeq proteins (6): NP_001123573, NP_001123574, NP_001238863, NP_001238864, NP_001350524, NP_005684* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000536Nucl_hrmn_rcpt_lig-bdDomain
IPR001628Znf_hrmn_rcptDomain
IPR001723Nuclear_hrmn_rcptFamily
IPR013088Znf_NHR/GATAHomologous_superfamily
IPR023257Liver_X_rcptFamily
IPR035500NHR-like_dom_sfHomologous_superfamily
IPR050234Nuclear_hormone_rcpt_NR1Family

Pfam: PF00104, PF00105

UniProt features (33 total): helix 11, region of interest 5, strand 3, splice variant 2, mutagenesis site 2, turn 2, zinc finger region 2, chain 1, domain 1, compositionally biased region 1, sequence variant 1, sequence conflict 1, DNA-binding region 1

Structure

Experimental structures (PDB)

7 structures.

PDBMethodResolution (Å)
5HJSX-RAY DIFFRACTION1.72
3IPQX-RAY DIFFRACTION2
3IPSX-RAY DIFFRACTION2.26
3IPUX-RAY DIFFRACTION2.4
5AVIX-RAY DIFFRACTION2.7
5AVLX-RAY DIFFRACTION2.8
1UHLX-RAY DIFFRACTION2.9

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q13133-F181.690.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

PositionPhenotype
268–273abolishes interaction with ncoa2 without affecting interaction with gps2; when associated with 438-a-a-439.
438–439abolishes interaction with ncoa2 without affecting interaction with gps2; when associated with 268-a–a-273.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

IDPathway
R-HSA-1989781PPARA activates gene expression
R-HSA-8866427VLDLR internalisation and degradation
R-HSA-9029558NR1H2 & NR1H3 regulate gene expression linked to lipogenesis
R-HSA-9029569NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-9031525NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake
R-HSA-9031528NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose
R-HSA-9623433NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis
R-HSA-9632974NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis
R-HSA-383280Nuclear Receptor transcription pathway
R-HSA-4090294SUMOylation of intracellular receptors

MSigDB gene sets: 488 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_DIGESTION, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_PINOCYTOSIS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_STEROL_HOMEOSTASIS

GO Biological Process (39): negative regulation of transcription by RNA polymerase II (GO:0000122), hormone-mediated signaling pathway (GO:0009755), negative regulation of macrophage derived foam cell differentiation (GO:0010745), positive regulation of triglyceride biosynthetic process (GO:0010867), positive regulation of cholesterol efflux (GO:0010875), regulation of lipid storage (GO:0010883), negative regulation of cholesterol storage (GO:0010887), cell differentiation (GO:0030154), intracellular receptor signaling pathway (GO:0030522), negative regulation of lipid transport (GO:0032369), positive regulation of cholesterol transport (GO:0032376), response to progesterone (GO:0032570), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), phosphatidylcholine acyl-chain remodeling (GO:0036151), cholesterol homeostasis (GO:0042632), regulation of circadian rhythm (GO:0042752), mRNA transcription by RNA polymerase II (GO:0042789), negative regulation of macrophage activation (GO:0043031), apoptotic cell clearance (GO:0043277), positive regulation of fatty acid biosynthetic process (GO:0045723), negative regulation of proteolysis (GO:0045861), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of lipid biosynthetic process (GO:0046889), negative regulation of pinocytosis (GO:0048550), negative regulation of inflammatory response (GO:0050728), lipid homeostasis (GO:0055088), sterol homeostasis (GO:0055092), negative regulation of type II interferon-mediated signaling pathway (GO:0060336), triglyceride homeostasis (GO:0070328), cellular response to lipopolysaccharide (GO:0071222), negative regulation of pancreatic juice secretion (GO:0090188), negative regulation of secretion of lysosomal enzymes (GO:0090341), negative regulation of cold-induced thermogenesis (GO:0120163), negative regulation of response to endoplasmic reticulum stress (GO:1903573), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), lipid metabolic process (GO:0006629), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (14): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), cholesterol binding (GO:0015485), chromatin DNA binding (GO:0031490), sterol response element binding (GO:0032810), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), signaling receptor complex (GO:0043235), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-5 pathways:

CategoryPathways
NR1H2 and NR1H3-mediated signaling6
Regulation of lipid metabolism by PPARalpha1
Plasma lipoprotein clearance1
Generic Transcription Pathway1
SUMO E3 ligases SUMOylate target proteins1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
regulation of transcription by RNA polymerase II2
transcription by RNA polymerase II2
positive regulation of lipid biosynthetic process2
DNA-binding transcription factor activity, RNA polymerase II-specific2
DNA binding2
negative regulation of DNA-templated transcription1
signal transduction1
cellular response to hormone stimulus1
macrophage derived foam cell differentiation1
regulation of macrophage derived foam cell differentiation1
negative regulation of cell differentiation1
regulation of triglyceride biosynthetic process1
triglyceride biosynthetic process1
positive regulation of triglyceride metabolic process1
regulation of cholesterol efflux1
positive regulation of cholesterol transport1
cholesterol efflux1
lipid storage1
regulation of cellular process1
cholesterol storage1
regulation of cholesterol storage1
negative regulation of lipid storage1
cellular developmental process1
intracellular signal transduction1
lipid transport1
regulation of lipid transport1
negative regulation of transport1
negative regulation of lipid localization1
cholesterol transport1
positive regulation of sterol transport1
regulation of cholesterol transport1
response to steroid hormone1
response to ketone1
toll-like receptor 4 signaling pathway1
regulation of toll-like receptor 4 signaling pathway1
positive regulation of pattern recognition receptor signaling pathway1
phosphatidylcholine metabolic process1
sterol homeostasis1

Protein interactions and networks

STRING

1856 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NR1H3ABCA1O95477935
NR1H3SREBF1P36956909
NR1H3SREBF2Q12772888
NR1H3XPR1Q9UBH6885
NR1H3NR0B2Q15466871
NR1H3CYP7A1P22680868
NR1H3ABCG1P45844863
NR1H3ABCG5Q9H222847
NR1H3ABCG8Q9H221832
NR1H3RXRAP19793813
NR1H3PPARGP37231763
NR1H3APOEP02649681
NR1H3STARP49675651
NR1H3CYP27A1Q02318645
NR1H3CYP8B1Q9UNU6645

IntAct

72 interactions, top by confidence:

ABTypeScore
NCOA1RXRApsi-mi:“MI:0915”(physical association)0.860
NR1H3RXRGpsi-mi:“MI:0915”(physical association)0.740
RXRGNR1H3psi-mi:“MI:0915”(physical association)0.740
NCOA1NR1H3psi-mi:“MI:0915”(physical association)0.690
NR1H3NCOA1psi-mi:“MI:0915”(physical association)0.690
NR1H3NCOA1psi-mi:“MI:0407”(direct interaction)0.690
NCOA1NR1H3psi-mi:“MI:0407”(direct interaction)0.690
NR1H3RXRBpsi-mi:“MI:0915”(physical association)0.670
RXRBNR1H3psi-mi:“MI:0915”(physical association)0.670
NR1H3NCOR1psi-mi:“MI:0407”(direct interaction)0.640
NCOR1NR1H3psi-mi:“MI:0914”(association)0.640
NR1H3NCOR1psi-mi:“MI:0914”(association)0.640
RXRANR1H3psi-mi:“MI:0407”(direct interaction)0.610
PPARANR1H3psi-mi:“MI:0407”(direct interaction)0.610
PPARANR1H3psi-mi:“MI:0915”(physical association)0.610
NR1H3RXRApsi-mi:“MI:0915”(physical association)0.610

BioGRID (91): NR1H3 (Two-hybrid), NR1H3 (Two-hybrid), NR1H3 (Two-hybrid), NR1H3 (Reconstituted Complex), STRN (Affinity Capture-MS), STRN3 (Affinity Capture-MS), STRN4 (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), PSMC5 (Two-hybrid), NCOA1 (Two-hybrid), RXRG (Two-hybrid), MDFI (Two-hybrid), NR1H3 (Two-hybrid), DDI2 (Affinity Capture-MS)

ESM2 similar proteins: A2T7D9, A3RGC1, O35627, O42295, O42450, O54915, O57606, O75469, P04625, P11473, P15204, P18113, P18115, P18117, P18119, P37242, P48281, P55055, P62044, P62045, P68305, P68306, Q02777, Q02965, Q13133, Q14994, Q1L673, Q28037, Q28570, Q28571, Q5E9B6, Q60644, Q62685, Q62755, Q8MIM3, Q8SQ01, Q90382, Q91241, Q91279, Q91424

Diamond homologs: A2T7D9, A2T928, A3RGC1, G5EFF5, O00482, O13124, O18531, O35627, O42101, O42295, O42392, O42450, O54915, O57606, O75469, O97716, P03373, P04625, P10276, P10827, P10828, P11416, P11473, P13053, P13631, P15204, P18113, P18115, P18117, P18119, P18514, P18911, P22448, P33242, P33244, P37242, P41235, P48281, P49700, P49701

SIGNOR signaling

5 interactions.

AEffectBMechanism
CSNK2A1down-regulatesNR1H3phosphorylation
“GW 3965”up-regulatesNR1H3“chemical activation”
ASXL3“down-regulates activity”NR1H3binding
NR0B2“down-regulates quantity by repression”NR1H3“transcriptional regulation”
NR1H3“up-regulates quantity by expression”BHLHE40“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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:

PathwayPartnersFoldFDR
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression6116.5×3e-10
NR1H2 and NR1H3-mediated signaling6112.5×3e-10
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux688.2×1e-09
Nuclear Receptor transcription pathway985.9×5e-14
R-HSA-400253582.4×5e-08
Expression of BMAL (ARNTL), CLOCK, and NPAS2569.7×1e-07
Activation of gene expression by SREBF (SREBP)561.8×2e-07
Cytoprotection by HMOX1652.6×2e-08

GO biological processes:

GO termPartnersFoldFDR
negative regulation of miRNA transcription5115.6×7e-08
hormone-mediated signaling pathway574.3×6e-07
mRNA transcription by RNA polymerase II673.4×3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance56
Likely benign6
Benign1

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
226296NM_005693.4(NR1H3):c.1244G>A (p.Arg415Gln)Pathogenic

SpliceAI

1716 predictions. Top by Δscore:

VariantEffectΔscore
11:47258106:G:GTdonor_gain1.0000
11:47258106:G:Tdonor_gain1.0000
11:47258116:G:GAdonor_gain1.0000
11:47260671:GGAGT:Gdonor_gain1.0000
11:47260672:GAGT:Gdonor_gain1.0000
11:47260672:GAGTG:Gdonor_gain1.0000
11:47260674:GT:Gdonor_gain1.0000
11:47260676:G:GGdonor_gain1.0000
11:47261236:CTTA:Cacceptor_loss1.0000
11:47261238:TA:Tacceptor_loss1.0000
11:47261240:GGT:Gacceptor_gain1.0000
11:47262015:GCAG:Gdonor_gain1.0000
11:47262016:CAGG:Cdonor_loss1.0000
11:47262017:AGGT:Adonor_loss1.0000
11:47262018:GGT:Gdonor_loss1.0000
11:47262019:GTG:Gdonor_loss1.0000
11:47262020:T:Adonor_loss1.0000
11:47267911:A:AGacceptor_gain1.0000
11:47267912:G:GGacceptor_gain1.0000
11:47268198:A:AGacceptor_gain1.0000
11:47268198:AATTT:Aacceptor_gain1.0000
11:47268199:A:Gacceptor_gain1.0000
11:47268547:CAGG:Cacceptor_loss1.0000
11:47268548:A:AGacceptor_gain1.0000
11:47268549:G:GGacceptor_gain1.0000
11:47268549:GGACC:Gacceptor_gain1.0000
11:47248720:C:CTdonor_gain0.9900
11:47258052:A:Tdonor_gain0.9900
11:47258105:GGAA:Gdonor_gain0.9900
11:47258107:A:Tdonor_gain0.9900

AlphaMissense

2937 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:47260468:T:AC98S1.000
11:47260468:T:CC98R1.000
11:47260469:G:AC98Y1.000
11:47260469:G:CC98S1.000
11:47260470:C:GC98W1.000
11:47260477:T:AC101S1.000
11:47260477:T:CC101R1.000
11:47260478:G:AC101Y1.000
11:47260478:G:CC101S1.000
11:47260479:T:GC101W1.000
11:47260496:G:AG107D1.000
11:47260498:T:CF108L1.000
11:47260500:C:AF108L1.000
11:47260500:C:GF108L1.000
11:47260501:C:AH109N1.000
11:47260501:C:GH109D1.000
11:47260503:C:AH109Q1.000
11:47260503:C:GH109Q1.000
11:47260504:T:CY110H1.000
11:47260516:A:CS114R1.000
11:47260518:C:AS114R1.000
11:47260518:C:GS114R1.000
11:47260519:T:AC115S1.000
11:47260519:T:CC115R1.000
11:47260520:G:AC115Y1.000
11:47260520:G:CC115S1.000
11:47260520:G:TC115F1.000
11:47260521:C:GC115W1.000
11:47260528:T:AC118S1.000
11:47260528:T:CC118R1.000

dbSNP variants (sampled 300 via entrez): RS1000022350 (11:47257992 C>G), RS1000196549 (11:47257014 G>A), RS1000214685 (11:47250638 A>C), RS1000233100 (11:47256869 T>C), RS1000525056 (11:47264015 C>G), RS1000532310 (11:47255563 T>A,C), RS1001182545 (11:47249389 T>A,C), RS1001286007 (11:47250589 CCTT>C), RS1001346422 (11:47252134 C>T), RS1001639153 (11:47269159 G>A), RS1001641299 (11:47258289 C>A), RS1001692654 (11:47265163 G>A,T), RS1001704003 (11:47264877 G>A), RS1001858682 (11:47260900 CAT>C), RS1001973575 (11:47262324 A>G,T)

Disease associations

OMIM: gene MIM:602423 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): multiple sclerosis (MONDO:0005301)

Orphanet (1): NON RARE IN EUROPE: Multiple sclerosis (Orphanet:802)

HPO phenotypes

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

GWAS associations

19 associations (top):

StudyTraitp-value
GCST000284_2HDL cholesterol4.000000e-08
GCST000755_37HDL cholesterol3.000000e-18
GCST001436_22Metabolic syndrome1.000000e-09
GCST004521_165Autism spectrum disorder or schizophrenia3.000000e-08
GCST004609_23Monocyte percentage of white cells4.000000e-11
GCST004632_26Lymphocyte percentage of white cells3.000000e-09
GCST005232_56Neuroticism1.000000e-16
GCST005985_32Creatinine levels2.000000e-08
GCST006412_120Intraocular pressure3.000000e-18
GCST006613_10Triglycerides1.000000e-22
GCST006940_78Neurociticism3.000000e-12
GCST006943_10Feeling miserable4.000000e-11
GCST007825_4Alzheimer’s disease or fasting glucose levels (pleiotropy)3.000000e-16
GCST008357_37Mood instability9.000000e-14
GCST009685_5Hypertension8.000000e-12
GCST010002_238Refractive error2.000000e-14
GCST010173_25Triglyceride levels6.000000e-19
GCST010661_1Blood glucose levels2.000000e-09
GCST010662_8Systolic blood pressure5.000000e-09

EFO canonical traits (11, from GWAS)

EFO IDTrait name
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0000195metabolic syndrome
EFO:0007989monocyte percentage of leukocytes
EFO:0007993lymphocyte percentage of leukocytes
EFO:0007660neuroticism measurement
EFO:0004695intraocular pressure measurement
EFO:0004530triglyceride measurement
EFO:0009598feeling miserable measurement
EFO:0008475mood instability measurement
EFO:0004468glucose measurement
EFO:0006335systolic blood pressure

MeSH disease descriptors (1)

DescriptorNameTree numbers
D009103Multiple SclerosisC10.114.375.500; C10.314.350.500; C20.111.258.250.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2808 (SINGLE PROTEIN), CHEMBL3430879 (PROTEIN COMPLEX), CHEMBL3706564 (PROTEIN FAMILY), CHEMBL3706565 (SELECTIVITY GROUP), CHEMBL6195519 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 266,307 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1023BEXAROTENE440,951
CHEMBL1082AMOXICILLIN4113,048
CHEMBL2103772RACECADOTRIL41,787
CHEMBL705ALITRETINOIN439,246
CHEMBL957BOSENTAN416,499
CHEMBL383634GLIQUIDONE29,480
CHEMBL44GENISTEIN244,212
CHEMBL4802158LARSUCOSTEROL2658
CHEMBL3360975BMS-779788145
CHEMBL3945199BMS-852927151
CHEMBL456237LXR-6231101
CHEMBL573677ABEQUOLIXRON1229

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

PharmGKB clinical annotations

3 annotations.

VariantTypeLevelDrugsPhenotypes
rs11039149Toxicity3atenolol;verapamilCoronary Artery Disease;Hypertension
rs12221497Toxicity3verapamilHypertension
rs2279238Toxicity3verapamilCoronary Artery Disease;Hypertension

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2279238MADD, NR1H332.251verapamil
rs11039149ACP2, NR1H332.751atenolol;verapamil
rs12221497NR1H332.251verapamil

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 1H. Liver X receptor-like receptors

Most potent curated ligand interactions (14 total), top 14:

LigandActionAffinityParameter
acetyl-podocarpic dimerAgonist9.0pEC50
AZ12260493Agonist8.15pKi
L-783483Agonist7.9pKd
T0901317Agonist7.3pEC50
27-hydroxycholesterolAgonist7.1pEC50
GSK2033Antagonist7.0pIC50
IMB-808Partial agonist6.82pEC50
GW3965Agonist6.7pEC50
SR9238Inverse agonist6.67pIC50
24(S), 25-epoxycholesterolAgonist6.5pEC50
desmosterolAgonist5.54pKi
paxillineAgonist5.4pEC50
24(S)-hydroxycholesterolAgonist5.4pEC50
22R-hydroxycholesterolAgonist5.3pEC50

Binding affinities (BindingDB)

511 measured of 599 human assays (617 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
(R)-5-chloro-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidineKI3 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(R)-5-bromo-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidineKI4 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
2-[4-({[3-(3-benzyl-8-chloroquinolin-4-yl)phenyl]amino}methyl)phenyl]acetic acidIC505 nM
(4-((S)-3-isopropyl-4-(((1r,4S)-4-methoxy-4-(trifluoromethyl)cyclohexyl)methyl)piperazin-1-yl)-2-(methylsulfonyl)phenyl)methanolKI5 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
biarylether alcohol quinoline, 5bIC505.2 nM
biarylether alcohol quinoline, 5iIC506.6 nM
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}acetic acidIC507 nM
2-{4-[({3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}acetic acidIC507.6 nM
2-{4-[({3-[3-phenyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}acetic acidIC508 nM
2-[4-({[3-(3-benzoyl-8-chloroquinolin-4-yl)phenyl]amino}methyl)phenyl]acetic acidIC509 nM
(R)-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-5-methoxy-4-(trifluoromethyl)pyrimidineKI9 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(R)-2-isopropyl-1-(6-methyl-5-(trifluoromethyl)pyridin-2-yl)-4-(3-(methylsulfonyl)phenyl)piperazineKI9 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
2-(4-{3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenoxymethyl}phenyl)acetic acidIC509.5 nM
biarylether alcohol quinoline, 5fIC5010.2 nM
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}acetamideIC5011 nM
biarylether amide quinoline, 4dIC5012 nM
biarylether amide quinoline, 4eIC5012 nM
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamideIC5013 nM
(R)-2-isopropyl-4-(3-(methylsulfonyl)phenyl)-1-(5-(trifluoromethyl)pyridin-2-yl)piperazineEC5013 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
2-{4-[3-({[2-chloro-3-(trifluoromethyl)phenyl]methyl}(2,2-diphenylethyl)amino)propoxy]-1H-indol-1-yl}acetic acidEC5014 nM
(R)-1-(6-cyclopropyl-5-(trifluoromethyl)pyridin-2-yl)-2-isopropyl-4-(3-(methylsulfonyl)phenyl)piperazineKI14 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
biarylether amide quinoline, 4gIC5015 nM
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}propanoic acidIC5015.2 nM
2-{4-[({3-[3-methyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}acetic acidIC5016 nM
2-(4-{3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxymethyl}phenyl)acetic acidIC5016.5 nM
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}-2-methylpropanoic acidIC5017.2 nM
2-[4-({[3-(3-benzoyl-8-methylquinolin-4-yl)phenyl]amino}methyl)phenyl]acetic acidIC5018 nM
{[2-chloro-3-(trifluoromethyl)phenyl]methyl}(2,2-diphenylethyl){3-[(1-methanesulfonyl-1H-indol-4-yl)oxy]propyl}amineEC5020 nM
biarylether amide quinoline, 4fIC5020 nM
2-[4-({[3-(3-benzyl-8-methylquinolin-4-yl)phenyl]amino}methyl)phenyl]acetic acidIC5021 nM
2-[2-[(1R)-8-(hydroxymethyl)-7-methylsulfonyl-1-propan-2-yl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-2-yl]-4-(trifluoromethyl)pyrimidin-5-yl]propan-2-olKI23 nMUS-9073931: Liver X receptor modulators
(1S,2R,5S,10S,11S,14R,15R)-14-[(2R)-6-hydroxy-6-methylheptan-2-yl]-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-5-olKD23 nM
{[2-chloro-3-(trifluoromethyl)phenyl]methyl}(2,2-diphenylethyl){3-[(5-methyl-1H-pyrazol-3-yl)oxy]propyl}amineEC5023 nM
ethyl 2-[8-(hydroxymethyl)-7-methylsulfonyl-1-propan-2-yl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-2-yl]-4-(trifluoromethyl)pyrimidine-5-carboxylateKI26 nMUS-9073931: Liver X receptor modulators
(R)-4-chloro-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-5-(trifluoromethyl)pyrimidineKI26 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
[2-[(2R)-4-[3-methylsulfonyl-4-(4-methyl-1,3-thiazol-2-yl)phenyl]-2-propan-2-ylpiperazin-1-yl]-4-(trifluoromethyl)pyrimidin-5-yl]methanolKI27 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
5-[(S)-(benzenesulfonyl)[(2R)-7-chloro-1H,2H,3H,4H-cyclopenta[b]indol-2-yl]fluoromethyl]-N,N-dimethyl-1,2,4-oxadiazol-3-amineIC5029 nM
(4-((S)-3-isopropyl-4-(((1s,4R)-4-methoxy-4-(trifluoromethyl)cyclohexyl)methyl)piperazin-1-yl)-2-(methylsulfonyl)phenyl)methanolKI30 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}-2,2-difluoroacetic acidIC5030.2 nM
(R)-2-(2-(4-(4-(hydroxymethyl)-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidin-5-yl)-2-methylpropanenitrileKI32 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
ethyl (R)-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isobutylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylateKI33 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
2-{3-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}acetic acidIC5033.6 nM
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}-2-hydroxyacetic acidIC5033.6 nM
2-{4-[({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amino)methyl]phenyl}ethan-1-olIC5034 nM
biarylether amide quinoline, 4nIC5034 nM
biarylether alcohol quinoline, 5eIC5036 nM
{[2-chloro-3-(trifluoromethyl)phenyl]methyl}(2,2-diphenylethyl){3-[(1-methyl-1H-indol-4-yl)oxy]propyl}amineEC5039 nM
(S)-(4-(4-((4,4-dimethylcyclohexyl)methyl)-3-phenylpiperazin-1-yl)-2-(methylsulfonyl)phenyl)methanolKI39 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
methyl 2-(2-(tert-butyl)-4-(4-fluoro-3-(methylsulfonyl)phenyl)piperazin-1-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylateKI41 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(R)-(4-(3-isopropyl-4-(6-(trifluoromethyl)pyridin-3-yl)piperazin-1-yl)-2-(methylsulfonyl)phenyl)methanolKI41 nMUS-10144715: Piperazine derivatives as liver X receptor modulators

ChEMBL bioactivities

1721 potent at pChembl≥5 of 1842 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.10EC500.08nMCHEMBL4764328
10.01EC500.098nMT091317
9.84EC500.145nMCHEMBL4756418
9.79EC500.161nMCHEMBL4745005
9.76EC500.174nMCHEMBL4764838
9.67EC500.214nMCHEMBL4747448
9.60EC500.251nMCHEMBL4749385
9.57EC500.27nMCHEMBL4797369
9.57EC500.27nMCHEMBL4762546
9.56EC500.277nMCHEMBL4760781
9.56EC500.274nMCHEMBL4757761
9.43EC500.372nMCHEMBL4755317
9.40EC500.401nMCHEMBL59030
9.37EC500.431nMLXR-623
9.32EC500.48nMCHEMBL3360966
9.15EC500.708nMCHEMBL4757158
9.10IC500.8nMCHEMBL595012
9.09IC500.81nMCHEMBL611735
9.07EC500.843nMCHEMBL4791199
9.04IC500.92nMCHEMBL592506
9.03EC500.928nMCHEMBL4748480
9.03EC500.94nMCHEMBL4777240
9.00EC501nMCHEMBL555373
9.00IC501nMCHEMBL365544
9.00EC501nMCHEMBL365544
9.00IC501nMCHEMBL384246
9.00EC501nMACETYL PODOCARPIC ACID ANHYDRIDE
9.00IC501nMCHEMBL595689
9.00IC501nMCHEMBL603636
8.97EC501.071nMCHEMBL4780872
8.96IC501.1nMCHEMBL595224
8.96IC501.1nMCHEMBL595782
8.93EC501.176nMCHEMBL4764539
8.92EC501.2nMBMS-779788
8.92IC501.2nMCHEMBL594062
8.92IC501.2nMCHEMBL606539
8.89IC501.3nMCHEMBL605730
8.85IC501.4nMCHEMBL593472
8.82IC501.5nMCHEMBL594063
8.80IC501.6nMCHEMBL593473
8.77IC501.7nMCHEMBL595936
8.76EC501.746nMCHEMBL4762542
8.74IC501.8nMCHEMBL595113
8.72IC501.9nMCHEMBL594175
8.71EC501.968nMCHEMBL4759393
8.71EC501.954nMCHEMBL4781683
8.70IC502nMCHEMBL555373
8.70IC502nMCHEMBL191965
8.70EC502nMCHEMBL191965
8.70IC502nMCHEMBL215108

PubChem BioAssay actives

1453 with measured affinity, of 3539 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.

CompoundAssayTypeValueUnit
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
(2’R,3R)-1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
(2’S,3S)-1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0002uM
1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0002uM
tert-butyl (2’R,3R)-2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0002uM
tert-butyl 2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0003uM
tert-butyl (2’R,3R)-2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0003uM
tert-butyl 2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0003uM
tert-butyl (2’S,3S)-2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0003uM
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0003uM
tert-butyl 2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0004uM
2-[(2-chloro-4-fluorophenyl)methyl]-3-(4-fluorophenyl)-7-(trifluoromethyl)indazole1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0004uM
2-[3-[3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0004uM
1-(2-chlorophenyl)-5-[4-(3-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazole1172007: Transactivation of LXR in human whole blood assessed as induction of ABCA1 after 4 hrs by SYBR-Green quantitative PCR analysisec500.0005uM
tert-butyl 2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0007uM
tert-butyl (2’S,3S)-2-oxo-2’-(3-phenylphenyl)spiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0008uM
2-benzyl-3-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)imidazo[1,2-a]pyridine454631: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0008uM
2-(2-methylpropyl)-1-[3-(3-methylsulfonylphenoxy)phenyl]-4-(trifluoromethyl)benzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0008uM
tert-butyl (2’S,3S)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0009uM
tert-butyl (2’S,3S)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0009uM
3-benzyl-4-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0009uM
2-[4-[benzyl(2,2,2-trifluoroethyl)amino]-3-chlorophenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol271504: Binding affinity to LXRalpha by radioligand displacement assayic500.0010uM
3-methyl-4-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0010uM
1-[3-(3-methylsulfonylphenoxy)phenyl]-2-propan-2-yl-4-(trifluoromethyl)benzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0010uM
[(4aS,10aR)-6-hydroxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl] 6-hydroxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate240151: Effective concentration against liver X receptor-alpha in HEK293 cell transactivation assayec500.0010uM
(4aS,10aR)-N-[(1S,4aS,10aR)-6-hydroxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl]-6-hydroxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxamide240218: Effective concentration for cofactor association with recombinant liver X receptor-alphaec500.0010uM
[(1S,4aS,10aR)-6-acetyloxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl] (1S,4aS,10aR)-6-acetyloxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate403099: Agonist activity at human recombinant LXRalpha expressed in Escherichia coli BL21 cells assessed as association of recombinant SRC1 to LXRalpha ligand binding domain by HTRF assayec500.0010uM
tert-butyl (2’R,3R)-2’-[3-(3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0011uM
8-chloro-3-methyl-4-[3-(3-methylsulfonylphenoxy)phenyl]quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0011uM
1-[3-(3-methylsulfonylphenoxy)phenyl]-2-phenyl-4-(trifluoromethyl)benzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0011uM
tert-butyl (2’R,3R)-2’-[3-[3-chloro-4-(dimethylcarbamoyl)phenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0012uM
3-benzyl-8-chloro-4-[3-(3-methylsulfonylphenoxy)phenyl]quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0012uM
2-[(4-fluorophenyl)methyl]-1-[3-(3-methylsulfonylphenoxy)phenyl]-4-(trifluoromethyl)benzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0012uM
2-[2-[2-(2-chlorophenyl)propan-2-yl]-1-[4-(3-methylsulfonylphenyl)phenyl]imidazol-4-yl]propan-2-ol1172007: Transactivation of LXR in human whole blood assessed as induction of ABCA1 after 4 hrs by SYBR-Green quantitative PCR analysisec500.0012uM
1-[3-(3-methylsulfonylphenoxy)phenyl]-2,4-bis(trifluoromethyl)benzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0013uM
3-[3-[3-[3-methyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy]phenyl]sulfonylpropan-1-ol451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0014uM
4-chloro-1-[3-(3-methylsulfonylphenoxy)phenyl]-2-propan-2-ylbenzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0015uM
4-[3-(3-ethylsulfonylphenoxy)phenyl]-3-methyl-8-(trifluoromethyl)quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0016uM
tert-butyl (2’S,3S)-2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0017uM
2-ethyl-1-[3-(3-methylsulfonylphenoxy)phenyl]-4-(trifluoromethyl)benzimidazole454924: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0017uM
3-methyl-4-[3-(3-propan-2-ylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0018uM
4-[3-(3-fluoro-5-methylsulfonylphenoxy)phenyl]-3-methyl-8-(trifluoromethyl)quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0019uM
2-[3-chloro-4-[[2-(3-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methyl-ethylamino]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol271504: Binding affinity to LXRalpha by radioligand displacement assayic500.0020uM
tert-butyl 2-oxo-2’-(3-phenylphenyl)spiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0020uM
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)phenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0020uM
[(1S,4aS,10aR)-6-acetyloxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl] (4aS,10aR)-6-acetyloxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate240218: Effective concentration for cofactor association with recombinant liver X receptor-alphaec500.0020uM
2-[4-[[3-[3-benzoyl-8-(trifluoromethyl)quinolin-5-yl]phenoxy]methyl]phenyl]-2-prop-2-ynylpent-4-ynoic acid313447: Binding affinity at human LXRalphaic500.0020uM
3-[[3-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methyl]-1,3-thiazolidine454631: Displacement of [3H]T0901317 from human recombinant LXRalpha LBDic500.0020uM
4-[3-(3-propan-2-ylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline451978: Displacement of [3H]T0901317 from human recombinant LXRalpha-LBDic500.0024uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
T0901317increases activity, affects cotreatment, increases abundance, affects reaction, increases reaction (+5 more)20
GW 3965increases activity, decreases expression, decreases reaction, affects cotreatment, increases expression (+1 more)6
Rosiglitazoneaffects reaction, increases expression, increases reaction, affects cotreatment6
22-hydroxycholesterolaffects cotreatment, affects localization, affects binding, increases activity, decreases reaction (+2 more)5
Valproic Acidaffects expression, decreases expression, affects cotreatment, increases expression, affects reaction (+1 more)4
Cyclosporinedecreases expression, affects cotreatment4
mono-(2-ethylhexyl)phthalateincreases reaction, increases expression, affects binding, increases activity3
Resveratrolincreases expression, increases reaction, decreases reaction3
Benzo(a)pyreneaffects methylation, decreases expression, increases methylation3
Dexamethasoneaffects cotreatment, increases expression, increases reaction3
bisphenol Aincreases expression, affects reaction2
25-hydroxycholesterolincreases transport, increases reaction, decreases reaction, affects binding, increases activity (+1 more)2
tributyltinaffects cotreatment, increases expression, increases reaction2
paxillineaffects cotreatment, increases expression, increases abundance, increases reaction2
Pioglitazoneincreases reaction, affects reaction, affects response to substance, increases expression2
Alitretinoinaffects localization, decreases reaction, increases expression, affects cotreatment2
Bexaroteneaffects cotreatment, increases expression, increases reaction, decreases expression2
Bezafibrateincreases activity, increases expression, increases reaction, increases transport, affects reaction (+2 more)2
Cholesterolaffects binding, increases activity, increases transport, increases reaction, affects cotreatment (+1 more)2
Nickeldecreases expression2
Fenofibrateaffects response to substance, affects cotreatment, affects expression, increases expression, affects reaction2
Aflatoxin B1affects expression, decreases expression2
GSK-J4decreases expression1
SR9238decreases reaction, increases activity1
bufotalindecreases expression1
methylmercuric chloridedecreases expression1
triphenyl phosphateincreases abundance, increases activity, decreases reaction1
pirinixic acidincreases activity, increases expression, affects binding1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphateaffects reaction, affects expression1
sodium arsenitedecreases expression1

ChEMBL screening assays

632 unique, capped per target: 500 binding, 106 functional, 19 admet, 7 toxicity

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1007705BindingDisplacement of [3H2]F3-methyl AA from human recombinant LXRalpha expressed in Escherichia coli BL21 cellsDiterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources. — J Nat Prod
CHEMBL1026572FunctionalAgonist activity at LXRalpha by FRET assay relative to GW-3965ASynthesis and SAR of potent LXR agonists containing an indole pharmacophore. — Bioorg Med Chem Lett
CHEMBL2176504ADMETTransactivational agonist activity at human LXRalpha transfected in HEK293 cells coexpressing CMX-Gal4N-DRIP205 assessed as DRIP205 recruitment at 10 uM after 16 hrs by mammalian two-hybrid assayDesign, synthesis, and biological evaluation of novel transrepression-selective liver X receptor (LXR) ligands with 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one skeleton. — J Med Chem

Cellosaurus cell lines

13 cell lines: 7 cancer cell line, 3 embryonic stem cell, 2 transformed cell line, 1 spontaneously immortalized cell line

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

CellosaurusNameCategorySex
CVCL_A4T3SEES3-1V human NR1H3, clone1Embryonic stem cellMale
CVCL_A4T4SEES3-1V human NR1H3, clone2Embryonic stem cellMale
CVCL_A4T5SEES3-1V human NR1H3, clone3Embryonic stem cellMale
CVCL_B8LLAbcam HCT 116 NR1H3 KOCancer cell lineMale
CVCL_B9NRAbcam A-549 NR1H3 KOCancer cell lineMale
CVCL_D2GQAbcam MCF-7 NR1H3 KOCancer cell lineFemale
CVCL_D7H4Ubigene HEK293T NR1H3 KOTransformed cell lineFemale
CVCL_E1L4HyCyte Hep-G2 KO-hNR1H3Cancer cell lineMale
CVCL_E2ELHAP1 NR1H3 (-) 1Cancer cell lineMale
CVCL_E2EMHAP1 NR1H3 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00037102PHASE4COMPLETEDCombination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis
NCT00037115PHASE4WITHDRAWNInduction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.
NCT00146068PHASE4COMPLETEDEARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00151294PHASE4TERMINATEDThe Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00176592PHASE4COMPLETEDPhase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
NCT00179478PHASE4COMPLETEDLong Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis
NCT00220922PHASE4COMPLETEDA Study to Evaluate the Impact on Skin (Injection Site) Reactions of Using Alcohol Wipes Prior to Daily Injections of Copaxone®.
NCT00239993PHASE4COMPLETEDA Study to Evaluate the Impact of Using Warm Compress Prior to Daily Injections of Copaxone®
NCT00240006PHASE4COMPLETEDA Study Comparing Shared Solutions® Plus MS Center Support Versus Shared Solutions® Alone
NCT00240032PHASE4COMPLETEDA Study to Evaluate the Impact on Skin (Injection Site) Reactions of Taking an Antihistamine (Zyrtec®) or Placebo Prior to Daily Injections of Copaxone®.
NCT00246324PHASE4COMPLETEDSafety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis
NCT00267319PHASE4COMPLETEDFOCUS Fatigue Outcome in Copaxone USers
NCT00381264PHASE4COMPLETEDEvaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Multiple Sclerosis
NCT00414453PHASE4TERMINATEDTrial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
NCT00423527PHASE4COMPLETEDLevetiracetam in Central Pain in Multiple Sclerosis(MS)
NCT00480181PHASE4COMPLETEDEfficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis
NCT00492765PHASE4COMPLETEDSimvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00493077PHASE4COMPLETEDSafety of Avonex Treatment in Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta Therapy
NCT00536120PHASE4COMPLETEDThe Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
NCT00629642PHASE4COMPLETEDClinical Study of Solifenacin Succinate in Patients With Bladder Symptoms Due to Spinal Cord Injury or Multiple Sclerosis
NCT00638027PHASE4COMPLETEDMemantine for Spasticity in MS Patients
NCT00744679PHASE4COMPLETEDA Pharmacokinetic (PK) Study of Natalizumab (Tysabri) at Steady State
NCT00752778PHASE4TERMINATEDMagnetic Resonance Imaging (MRI) Follow-up of Macrophagic Infiltration in MS Patients Treated With Tysabri
NCT00753792PHASE4COMPLETEDOral Corticotherapy in Megadoses to Treat Multiple Sclerosis During Relapse
NCT00854750PHASE4TERMINATEDModeling and Treating the Pathophysiology of Demyelination in Multiple Sclerosis
NCT00881205PHASE4TERMINATEDRivastigmine in Multiple Sclerosis Patients With Cognitive Impairment
NCT00910598PHASE4UNKNOWNOptical Coherence Tomography: Glatiramer in Clinically Isolated Syndrome or Early Relapsing Remitting Multiple Sclerosis (MS)
NCT00913666PHASE4COMPLETEDPharmacodynamic Study to Better Understand the Therapeutic Response and Immunomodulatory Effects of Avonex in Multiple Sclerosis (MS) Patients and Healthy Volunteers
NCT00915460PHASE4COMPLETEDOpen-Label Safety Extension Study of Avonex
NCT00942214PHASE4COMPLETEDBiomarkers and Response to Natalizumab for Multiple Sclerosis Treatment
NCT00988988PHASE4WITHDRAWNThe Effects of Ethyl-Alpha-Guanido-Methyl Ethanoate on Skin Reactions From Glatiramer Acetate Injections
NCT01005095PHASE4TERMINATEDThe Effects of Interferon Beta Combined With Vitamin D on Relapsing Remitting Multiple Sclerosis Patients
NCT01034579PHASE4COMPLETEDThe REbif® vs Glatiramer Acetate in Relapsing Multiple Sclerosis Pharmacogenetics Trial
NCT01085318PHASE4COMPLETEDRebif Advanced Magnetic Resonance Imaging (MRI) and Immunology Pilot Trial
NCT01236534PHASE4COMPLETEDLubiprostone in Patients With Multiple Sclerosis Associated Constipation
NCT01333501PHASE4COMPLETEDFingolimod Versus Interferon Beta 1b in Cognitive Symptoms
NCT01339676PHASE4UNKNOWNColecalciferol as an Add-on Treatment to Interferon-beta-1b for Treatment of Multiple Sclerosis (MS)
NCT01356940PHASE4COMPLETEDA Placebo Controlled Trial of Dalfampridine ER for Ambulatory Activity in People With Multiple Sclerosis
NCT01395316PHASE4COMPLETEDAlemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis
NCT01411514PHASE4TERMINATEDOral Prednisone Taper Versus Placebo for the Treatment of Acute Relapses in Multiple Sclerosis

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot