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Atlas / Gene / NR1H2

NR1H2

gene
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Also known as NERNER-IRIP15LXR-bLXRb

Summary

NR1H2 (nuclear receptor subfamily 1 group H member 2, HGNC:7965) is a protein-coding gene on chromosome 19q13.3, encoding Oxysterols receptor LXR-beta (P55055). Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity.

The liver X receptors, LXRA (NR1H3; MIM 602423) and LXRB, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRA is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRB is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs; see MIM 180245) and regulate expression of target genes containing LXR response elements (summary by Korf et al., 2009 [PubMed 19436111]).

Source: NCBI Gene 7376 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 33 total
  • Druggable target: yes — 12 molecules with ChEMBL bioactivity
  • Transcription factor: yes — 52 downstream targets (CollecTRI)
  • MANE Select transcript: NM_007121

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7965
Approved symbolNR1H2
Namenuclear receptor subfamily 1 group H member 2
Location19q13.3
Locus typegene with protein product
StatusApproved
AliasesNER, NER-I, RIP15, LXR-b, LXRb
Ensembl geneENSG00000131408
Ensembl biotypeprotein_coding
OMIM600380
Entrez7376

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 38 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000253727, ENST00000411902, ENST00000593532, ENST00000593926, ENST00000595730, ENST00000597085, ENST00000597130, ENST00000597157, ENST00000597790, ENST00000598168, ENST00000599105, ENST00000600355, ENST00000600978, ENST00000652203, ENST00000852420, ENST00000852421, ENST00000852422, ENST00000852423, ENST00000852424, ENST00000852425, ENST00000939061, ENST00000939062, ENST00000939063, ENST00000939064, ENST00000939065, ENST00000939066, ENST00000939067, ENST00000939068, ENST00000939069, ENST00000939070, ENST00000939071, ENST00000939072, ENST00000939073, ENST00000967767, ENST00000967768, ENST00000967769, ENST00000967770, ENST00000967771, ENST00000967772, ENST00000967773, ENST00000967774, ENST00000967775

RefSeq mRNA: 2 — MANE Select: NM_007121 NM_001256647, NM_007121

CCDS: CCDS42593, CCDS58673

Canonical transcript exons

ENST00000253727 — 10 exons

ExonStartEnd
ENSE000009003415037814950378439
ENSE000009003475037900250379181
ENSE000013829655037671950376826
ENSE000031325825037645750376576
ENSE000031482675038245650383388
ENSE000034903535037758750377648
ENSE000035155485037773350377870
ENSE000035500455037978050379879
ENSE000036559715037852250378796
ENSE000036795885038196650382174

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.9599 / max 557.7889, expressed in 1824 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
17714244.81201824
1771391.2229412
1771340.5496261
1771330.2652136
1771350.073428
1771430.036820

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
popliteal arteryUBERON:000225097.52gold quality
tibial arteryUBERON:000761097.51gold quality
lower esophagus muscularis layerUBERON:003583397.24gold quality
lower esophagusUBERON:001347397.22gold quality
aortaUBERON:000094797.16gold quality
right coronary arteryUBERON:000162597.07gold quality
esophagogastric junction muscularis propriaUBERON:003584197.02gold quality
thoracic aortaUBERON:000151596.94gold quality
left coronary arteryUBERON:000162696.92gold quality
ascending aortaUBERON:000149696.90gold quality
descending thoracic aortaUBERON:000234596.89gold quality
mucosa of stomachUBERON:000119996.80gold quality
gastrocnemiusUBERON:000138896.75gold quality
hindlimb stylopod muscleUBERON:000425296.75gold quality
right lungUBERON:000216796.70gold quality
left uterine tubeUBERON:000130396.63gold quality
muscle layer of sigmoid colonUBERON:003580596.58gold quality
apex of heartUBERON:000209896.52gold quality
coronary arteryUBERON:000162196.24gold quality
muscle of legUBERON:000138396.23gold quality
right uterine tubeUBERON:000130295.98gold quality
granulocyteCL:000009495.95gold quality
endocervixUBERON:000045895.93gold quality
upper lobe of left lungUBERON:000895295.79gold quality
body of uterusUBERON:000985395.71gold quality
monocyteCL:000057695.54gold quality
left lobe of thyroid glandUBERON:000112095.54gold quality
right atrium auricular regionUBERON:000663195.51gold quality
body of stomachUBERON:000116195.46gold quality
heart left ventricleUBERON:000208495.41gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes16.89

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

52 targets.

TargetRegulation
ABCA1Activation
ABCG1Activation
ABCG4Activation
ABCG5Activation
ABCG8Activation
ACSL3Activation
APOEActivation
AQP1Unknown
BHLHE40Activation
C3Activation
CD36Activation
CD74
CETPRepression
CLC
CYP7A1Activation
CYP7B1Repression
DHCR24
ENHORepression
ERCC2
ERCC3
F3
FBP1Repression
FGF21
FOXM1Activation
G6PC1Repression
GCKUnknown
HK1
INSActivation
INSIG2Activation
KAT2A

JASPAR motifs

MotifNameFamily
MA0115.1NR1H2::RXRAThyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:10187832

Upstream regulators (CollecTRI, top): ELK1, ETS1, NFKB, NR0B2, NR1H2, NR1H3, PITX2, RBPJ, SREBF2, SRF

miRNA regulators (miRDB)

38 targeting NR1H2, 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-5692A100.0074.406850
HSA-MIR-4476100.0068.182030
HSA-MIR-6876-5P100.0067.682126
HSA-MIR-426799.9666.532368
HSA-MIR-6825-5P99.9669.813431
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-548E-5P99.8972.734486
HSA-MIR-449299.8768.253611
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-149-3P99.7268.223963
HSA-MIR-6883-5P99.6968.053785
HSA-MIR-7-5P99.6770.531809
HSA-MIR-6887-3P99.6667.831778
HSA-MIR-7152-5P99.6069.332094
HSA-MIR-76299.5866.611994
HSA-MIR-4761-5P99.5166.69804
HSA-MIR-449899.4767.422360
HSA-MIR-4652-3P99.3370.022742
HSA-MIR-18A-5P99.2971.05806
HSA-MIR-18B-5P99.2971.05806
HSA-MIR-3692-5P99.2967.041421
HSA-MIR-4735-3P99.1469.85777
HSA-MIR-312599.1468.492269
HSA-MIR-5001-5P99.0566.761972
HSA-MIR-6814-5P99.0366.681273
HSA-MIR-391698.9968.042155
HSA-MIR-6859-5P98.9968.072049
HSA-MIR-4477A98.8369.752952
HSA-MIR-468698.7766.87964

Literature-anchored findings (GeneRIF, showing 40)

  • regulated AKL-1 signaling (PMID:12393874)
  • X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch. (PMID:12736258)
  • 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)
  • X-ray crystal structure of the liver X receptor beta ligand-binding domain in complex with a synthetic agonist, T-0901317 (PMID:14643652)
  • LXRalpha and LXRbeta regulate transcription of the vascular endothelial growth factor gene in macrophages (PMID:14699103)
  • 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)
  • These results show that LXR stimulated preferentially triglyceride accumulation in human preadipocytes via the induction of de novo lipogenesis, rather than activating the differentiation process through PPARgamma activation. (PMID:16298468)
  • 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)
  • 24(S)-hydroxycholesterol induces apoE-mediated efflux of cholesterol in astrocytes via an LXR-controlled pathway (PMID:16524875)
  • Data demonstrate that LXR-beta activation altered all of the cellular cholesterol fluxes. (PMID:16567856)
  • Results provide evidence that liver X receptors alpha and beta are phosphorylated proteins. (PMID:16904112)
  • 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)
  • This suggests ABCC6 gene expression and the first identification of a transcription factor which is relevant to regulation of ABCC6 level in tissues and in some PXE patients. (PMID:17045963)
  • 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)
  • 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)
  • Glucose significantly induces transcription via the LXRB gene promoter and that the identified binding sites are important for proper glucose responsiveness. (PMID:17626048)
  • It was proposed that LXR is a key regulator of cytokine release in LPS-challenged human monocytes, possibly by interfering with translational events. (PMID:17724434)
  • In summary, this study is the first to demonstrate anti-inflammatory actions of LXRs in the lung. (PMID:17766241)
  • LXRalpha and LXRbeta are expresed in the majority of the cell types in human skin. . (PMID:17845217)
  • Subjects carrying both the CD14 (-260) C/C and the LXRbeta (intron 5) G/G genotypes had a six times lower risk of developing AD than subjects without these risk genotypes. These data support a role for innate immune response genes in risk for AD. (PMID:17900622)
  • none of the SNPs typed for NAT2, ERCC1, ERCC4 and ERCC6 showed significant association with risk (PMID:18026184)
  • The current study of a Spanish population does not demonstrate an association between LXRbeta genotypes or haplotypes and Alzheimer’s disease. (PMID:18081155)
  • review of role of activation of PPARalpha, -beta/delta, or -gamma or LXRs in skin physiology and cytology and disease (PMID:18182682)
  • Analysis of the protein-ligand complexes of X-ray crystallography-derived structures revealed that residues His435 and Trp457 act as a switch that mediates ligand activation (PMID:18221307)
  • nuclear liver X receptor-beta interaction with ABCA1 modulates cholesterol efflux (PMID:18782758)
  • 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. (PMID:18854425)
  • mediates HBV-associated hepatic steatosis (PMID:19105208)
  • SREBP-1c expression increases during keratinocyte differentiation, and LXR activation enhances its expression (PMID:19242521)
  • Variations in the LXRB gene promoter may be part of the aetiology of type 2 diabetes (PMID:19292929)
  • modulation of cholesterol metabolism via intraluminal phospholipids is related to the activity of the oxysterol nuclear receptor LXR (PMID:19303409)
  • LXR-activating oxysterols induce the expression of inflammatory markers in endothelial cells through LXR-independent mechanisms. (PMID:19426978)
  • Data describe the requirement of GPS2 for ABCG1 gene transcription and cholesterol efflux from macrophages, and implicate GPS2 in facilitating LXRalpha/beta recruitment to an ABCG1-specific promoter/enhancer unit upon ligand activation. (PMID:19481530)
  • Deletion of liver X receptors (Lxralpha and beta) reduced cell cycle progression and ventral midbrain neurogenesis, resulting in decreased dopaminergic neurons at birth. (PMID:19796621)

Cross-species orthologs

187 orthologs

OrganismSymbolGene ID
mus_musculusNr1h2ENSMUSG00000060601
rattus_norvegicusNr1h2ENSRNOG00000019812
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), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), 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-beta — P55055 (reviewed: P55055)

Alternative names: Liver X receptor beta, Nuclear receptor NER, Nuclear receptor subfamily 1 group H member 2, Ubiquitously-expressed nuclear receptor

All UniProt accessions (8): P55055, M0QYE6, M0QZF5, M0R0K3, M0R1V8, M0R229, M0R2F9, M0R3A7

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5’-AGGTCA-3’ and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR 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. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex.

Subunit / interactions. Forms a heterodimer with RXR. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation. Interacts with ABCA12 and ABCA1; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Sumoylated by SUMO2 at Lys-409 and Lys-447 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation.

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

Isoforms (2)

UniProt IDNamesCanonical?
P55055-11yes
P55055-22

RefSeq proteins (2): NP_001243576, NP_009052* (*=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 (49 total): helix 16, strand 7, turn 5, compositionally biased region 4, region of interest 4, cross-link 2, mutagenesis site 2, sequence conflict 2, zinc finger region 2, chain 1, domain 1, splice variant 1, sequence variant 1, DNA-binding region 1

Structure

Experimental structures (PDB)

25 structures.

PDBMethodResolution (Å)
6S5KX-RAY DIFFRACTION1.6
6S4NX-RAY DIFFRACTION1.9
6S4TX-RAY DIFFRACTION2
4RAKX-RAY DIFFRACTION2.04
1PQ9X-RAY DIFFRACTION2.1
1UPVX-RAY DIFFRACTION2.1
3L0EX-RAY DIFFRACTION2.3
1PQ6X-RAY DIFFRACTION2.4
1UPWX-RAY DIFFRACTION2.4
3KFCX-RAY DIFFRACTION2.4
5JY3X-RAY DIFFRACTION2.4
4DK7X-RAY DIFFRACTION2.45
6K9HX-RAY DIFFRACTION2.5
5KYAX-RAY DIFFRACTION2.6
5HJPX-RAY DIFFRACTION2.6
6JIOX-RAY DIFFRACTION2.6
5I4VX-RAY DIFFRACTION2.61
4DK8X-RAY DIFFRACTION2.75
1P8DX-RAY DIFFRACTION2.8
1PQCX-RAY DIFFRACTION2.8
5KYJX-RAY DIFFRACTION2.8
6K9GX-RAY DIFFRACTION2.8
6S4UX-RAY DIFFRACTION2.81
6K9MX-RAY DIFFRACTION2.9
4NQAX-RAY DIFFRACTION3.1

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P55055-F181.770.62

Functional residue map

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

Post-translational modifications (2): 409, 447

Mutagenesis-validated functional residues (2):

PositionPhenotype
409impaired ability to act as an anti-inflammatory role during the hepatic acute phase response; when associated with r-447
447impaired ability to act as an anti-inflammatory role during the hepatic acute phase response; when associated with r-409

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

IDPathway
R-HSA-1989781PPARA activates gene expression
R-HSA-383280Nuclear Receptor transcription pathway
R-HSA-4090294SUMOylation of intracellular receptors
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

MSigDB gene sets: 371 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GCACCTT_MIR18A_MIR18B, 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, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (37): negative regulation of transcription by RNA polymerase II (GO:0000122), hormone-mediated signaling pathway (GO:0009755), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), 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), positive regulation of lipid storage (GO:0010884), negative regulation of cholesterol storage (GO:0010887), cell differentiation (GO:0030154), intracellular receptor signaling pathway (GO:0030522), response to nutrient levels (GO:0031667), negative regulation of lipid transport (GO:0032369), positive regulation of cholesterol transport (GO:0032376), phosphatidylcholine acyl-chain remodeling (GO:0036151), cholesterol homeostasis (GO:0042632), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of fatty acid biosynthetic process (GO:0045723), negative regulation of proteolysis (GO:0045861), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), retinoic acid receptor signaling pathway (GO:0048384), negative regulation of pinocytosis (GO:0048550), negative regulation of inflammatory response (GO:0050728), negative regulation of type II interferon-mediated signaling pathway (GO:0060336), positive regulation of high-density lipoprotein particle assembly (GO:0090108), positive regulation of pancreatic juice secretion (GO:0090187), positive regulation of secretion of lysosomal enzymes (GO:0090340), negative regulation of cold-induced thermogenesis (GO:0120163), positive regulation of miRNA transcription (GO:1902895), 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), lipid homeostasis (GO:0055088)

GO Molecular Function (14): 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), chromatin DNA binding (GO:0031490), apolipoprotein A-I receptor binding (GO:0034191), nuclear retinoid X receptor binding (GO:0046965), ATPase binding (GO:0051117), 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 (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-5 pathways:

CategoryPathways
NR1H2 and NR1H3-mediated signaling5
Regulation of lipid metabolism by PPARalpha1
Generic Transcription Pathway1
SUMO E3 ligases SUMOylate target proteins1
Plasma lipoprotein clearance1

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
gene expression2
regulation of gene expression2
positive regulation of lipid biosynthetic process2
lipid storage2
DNA-binding transcription factor activity, RNA polymerase II-specific2
DNA binding2
negative regulation of DNA-templated transcription1
signal transduction1
cellular response to hormone stimulus1
positive regulation of macromolecule biosynthetic process1
negative regulation of macromolecule biosynthetic process1
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
regulation of cellular process1
regulation of lipid storage1
positive regulation of cellular process1
positive regulation of lipid localization1
cholesterol storage1
regulation of cholesterol storage1
negative regulation of lipid storage1
cellular developmental process1
intracellular signal transduction1
response to stimulus1
lipid transport1
regulation of lipid transport1
negative regulation of transport1
negative regulation of lipid localization1
cholesterol transport1
positive regulation of sterol transport1

Protein interactions and networks

STRING

1374 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NR1H2XPR1Q9UBH6932
NR1H2ABCA1O95477900
NR1H2RXRAP19793827
NR1H2ABCG5Q9H222822
NR1H2SREBF2Q12772820
NR1H2ABCG8Q9H221803
NR1H2ABCG1P45844782
NR1H2SREBF1P36956697
NR1H2CYP7A1P22680687
NR1H2SULT2B1O00204678
NR1H2APOEP02649604
NR1H2MYLIPQ8WY64519
NR1H2ABCB5Q2M3G0516
NR1H2CD5LO43866504
NR1H2NCOA6Q14686501

IntAct

66 interactions, top by confidence:

ABTypeScore
NR1H2RXRGpsi-mi:“MI:0915”(physical association)0.810
RXRGNR1H2psi-mi:“MI:0915”(physical association)0.810
NCOA2RXRApsi-mi:“MI:0915”(physical association)0.780
NR1H2MDFIpsi-mi:“MI:0915”(physical association)0.620
MDFINR1H2psi-mi:“MI:0915”(physical association)0.620
RXRANR1H2psi-mi:“MI:0407”(direct interaction)0.590
RXRANR1H2psi-mi:“MI:0915”(physical association)0.590
CORO2ANR1H2psi-mi:“MI:0915”(physical association)0.580
NR1H2CORO2Apsi-mi:“MI:0915”(physical association)0.580
RXRGNR2F6psi-mi:“MI:0914”(association)0.530
SLC30A2ESYT2psi-mi:“MI:0914”(association)0.530
NR1H2NCOR1psi-mi:“MI:0407”(direct interaction)0.520
NCOR1NR1H2psi-mi:“MI:0914”(association)0.520
NR1H2MED1psi-mi:“MI:0407”(direct interaction)0.440
NR1H2CAMK2Gpsi-mi:“MI:0217”(phosphorylation reaction)0.440
NR1H2CIDEApsi-mi:“MI:0407”(direct interaction)0.440
NR1H2ABCA1psi-mi:“MI:0914”(association)0.420
ABCA1NR1H2psi-mi:“MI:2364”(proximity)0.420
MEN1NR1H2psi-mi:“MI:0915”(physical association)0.400
NR1H2Senp3psi-mi:“MI:0915”(physical association)0.400

BioGRID (106): NR1H2 (Two-hybrid), NR1H2 (Two-hybrid), NR1H2 (Affinity Capture-Western), NR1H2 (Two-hybrid), NCOA1 (Two-hybrid), NR1H2 (Affinity Capture-Western), NR1H2 (Reconstituted Complex), NR1H2 (Reconstituted Complex), NR1H2 (Two-hybrid), NR1H2 (Affinity Capture-MS), NR0B2 (Affinity Capture-Western), PIAS1 (Affinity Capture-Western), STAT1 (Affinity Capture-Western), NR1H2 (Two-hybrid), NR1H2 (Reconstituted Complex)

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: A2T928, A2T929, A4IIG7, O35507, O42295, O42450, O57606, O77245, O97716, P03373, P04625, P10276, P10826, P10827, P10828, P11416, P12813, P13631, P15204, P17671, P18113, P18115, P18117, P18119, P18514, P18515, P18516, P18911, P19793, P22448, P22605, P22736, P22829, P28699, P28700, P28701, P28702, P28704, P28705, P37242

SIGNOR signaling

4 interactions.

AEffectBMechanism
RXRAup-regulatesNR1H2binding
RXRBup-regulatesNR1H2binding
NR0B2“down-regulates quantity by repression”NR1H2“transcriptional regulation”
NR1H2“up-regulates quantity by expression”BHLHE40“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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 expression556.6×3e-06
NR1H2 and NR1H3-mediated signaling554.7×3e-06
R-HSA-400253548.1×4e-06
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux542.9×5e-06
Nuclear Receptor transcription pathway633.4×3e-06
Regulation of lipid metabolism by PPARalpha623.5×8e-06
Signaling by Nuclear Receptors822.7×6e-07
Epigenetic regulation by WDR5-containing histone modifying complexes521.4×1e-04

GO biological processes:

GO termPartnersFoldFDR
mRNA transcription by RNA polymerase II535.9×1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance15
Likely benign3
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2848 predictions. Top by Δscore:

VariantEffectΔscore
19:50358781:C:CCacceptor_gain1.0000
19:50359110:C:CCacceptor_gain1.0000
19:50359646:CA:Cacceptor_gain1.0000
19:50359648:C:CCacceptor_gain1.0000
19:50359738:A:ACdonor_gain1.0000
19:50359739:C:CCdonor_gain1.0000
19:50359739:CCG:Cdonor_gain1.0000
19:50360769:T:TAdonor_gain1.0000
19:50360811:T:TAdonor_gain1.0000
19:50360854:T:TAdonor_gain1.0000
19:50360875:T:TAdonor_gain1.0000
19:50362170:A:ACdonor_gain1.0000
19:50362170:ACATC:Adonor_gain1.0000
19:50362171:C:CCdonor_gain1.0000
19:50362171:CAT:Cdonor_gain1.0000
19:50362171:CATCC:Cdonor_gain1.0000
19:50362174:C:Adonor_gain1.0000
19:50362309:GGATG:Gacceptor_gain1.0000
19:50362314:C:CCacceptor_gain1.0000
19:50376576:GGT:Gdonor_loss1.0000
19:50376577:G:GAdonor_loss1.0000
19:50376578:T:Adonor_loss1.0000
19:50378147:A:AGacceptor_gain1.0000
19:50378148:G:GAacceptor_gain1.0000
19:50378408:C:Tdonor_gain1.0000
19:50378418:G:GTdonor_gain1.0000
19:50378425:GGA:Gdonor_gain1.0000
19:50378426:G:Tdonor_gain1.0000
19:50378432:G:GTdonor_gain1.0000
19:50378435:GCAGT:Gdonor_gain1.0000

AlphaMissense

2982 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
19:50378226:T:AC87S1.000
19:50378226:T:CC87R1.000
19:50378227:G:AC87Y1.000
19:50378227:G:CC87S1.000
19:50378228:C:GC87W1.000
19:50378235:T:AC90S1.000
19:50378235:T:CC90R1.000
19:50378236:G:AC90Y1.000
19:50378236:G:CC90S1.000
19:50378259:C:GH98D1.000
19:50378261:C:AH98Q1.000
19:50378261:C:GH98Q1.000
19:50378262:T:CY99H1.000
19:50378274:A:CS103R1.000
19:50378276:C:AS103R1.000
19:50378276:C:GS103R1.000
19:50378277:T:AC104S1.000
19:50378277:T:CC104R1.000
19:50378278:G:AC104Y1.000
19:50378278:G:CC104S1.000
19:50378278:G:TC104F1.000
19:50378279:C:GC104W1.000
19:50378286:T:AC107S1.000
19:50378286:T:CC107R1.000
19:50378287:G:AC107Y1.000
19:50378287:G:CC107S1.000
19:50378287:G:TC107F1.000
19:50378288:C:GC107W1.000
19:50378290:A:TK108M1.000
19:50378291:G:CK108N1.000

dbSNP variants (sampled 300 via entrez): RS1000022251 (19:50380396 G>A), RS1000159721 (19:50376247 G>A), RS1000300894 (19:50377352 G>A), RS1000609313 (19:50380209 A>C), RS1000646313 (19:50383858 G>C), RS1000911565 (19:50383741 T>A,C), RS1001001507 (19:50379483 T>A,C), RS1001053854 (19:50379303 C>T), RS1001285944 (19:50383223 T>C), RS1001508320 (19:50383084 G>A), RS1001667010 (19:50375268 C>G,T), RS1001802174 (19:50379695 T>A,G), RS1002012806 (19:50375540 C>G,T), RS1002315401 (19:50375133 CTT>C), RS1002369852 (19:50383152 G>A)

Disease associations

OMIM: gene MIM:600380 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3430878 (PROTEIN COMPLEX), CHEMBL3706564 (PROTEIN FAMILY), CHEMBL3706565 (SELECTIVITY GROUP), CHEMBL4093 (SINGLE PROTEIN), CHEMBL6193828 (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: 336,058 (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
CHEMBL157101KETOCONAZOLE475,361
CHEMBL1789941RUXOLITINIB411,547
CHEMBL2103772RACECADOTRIL41,787
CHEMBL705ALITRETINOIN439,246
CHEMBL383634GLIQUIDONE29,480
CHEMBL44GENISTEIN244,212
CHEMBL3360975BMS-779788145
CHEMBL3945199BMS-852927151
CHEMBL456237LXR-6231101
CHEMBL573677ABEQUOLIXRON1229

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs2695121Toxicity3gefitinibDiarrhea;Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2695121NR1H232.001gefitinib

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 (17 total), top 17:

LigandActionAffinityParameter
acetyl-podocarpic dimerAgonist9.0pEC50
L-783483Agonist8.2pKd
BMS-852927Agonist8.05pEC50
AZ12260493Agonist7.96pKi
GW3965Agonist7.52pEC50
GSK9772Agonist7.52pIC50
GSK2033Antagonist7.5pIC50
SR9238Inverse agonist7.37pIC50
T0901317Agonist7.3pEC50
27-hydroxycholesterolAgonist7.15pEC50
24(S), 25-epoxycholesterolAgonist7.04pEC50
IMB-808Partial agonist6.28pEC50
rovazolacAgonist6.0pEC50
desmosterolAgonist5.85pKi
compound 17l [PMID: 26288691]Antagonist5.74pIC50
22R-hydroxycholesterolAgonist5.52pEC50
24(S)-hydroxycholesterolAgonist5.5pEC50

Binding affinities (BindingDB)

597 measured of 708 human assays (726 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
(R)-(4-(3-isopropyl-4-(5-(prop-1-en-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)-2-(methylsulfonyl)phenyl)methanolKI1 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(R)-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-5-((methylthio)methyl)-4-(trifluoromethyl)pyrimidineKI1 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(R)-5-cyclopropyl-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidineKI1 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(S)-2-isopropyl-4-(3-(methylsulfonyl)phenyl)-1-(((1s,4R)-4-(trifluoromethyl)cyclohexyl)methyl)piperazineKI2 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(R)-5-(4-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-3-isopropylpiperazin-1-yl)-2-fluoro-N-methylbenzenesulfonamideKI3 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(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)-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-methyl-5-(trifluoromethyl)pyrimidineKI3 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)-4-(trifluoromethyl)pyrimidine-5-carbonitrileKI9 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(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
ethyl (R)-2-(2-cyclopropyl-4-(4-fluoro-3-(methylsulfonyl)phenyl)piperazin-1-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylateKI13 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
(R)-5-bromo-2-(2-isopropyl-4-(3-(methylsulfonyl)phenyl)piperazin-1-yl)pyrimidineEC5016 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
methyl (R)-2-(4-(4-fluoro-3-(N-(4-methoxybenzyl)-N-methylsulfamoyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylateKI16 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
2-(4-{3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxymethyl}phenyl)acetic acidIC5016.5 nM
ethyl 2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-(2,2,2-trifluoroethyl)piperazin-1-yl)-4-methylpyrimidine-5-carboxylateKI17 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
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
{[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
(S)-2-(2-chlorophenyl)-4-(3-(methylsulfonyl)phenyl)-1-(((1r,4S)-4-(trifluoromethyl)cyclohexyl)methyl)piperazineKI27 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
1-(3-bromo-4-(trifluoromethyl)benzyl)-4-(3-(methylsulfonyl)phenyl)-2-phenylpiperazineKI30 nMUS-10144715: Piperazine derivatives as liver X receptor modulators
(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

ChEMBL bioactivities

2038 potent at pChembl≥5 of 2143 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.80EC500.016nMCHEMBL4764328
10.46EC500.035nMCHEMBL4756418
10.28EC500.052nMCHEMBL4764838
10.17EC500.067nMCHEMBL4747448
10.08EC500.083nMCHEMBL4745005
10.06EC500.088nMCHEMBL4797369
10.04EC500.092nMCHEMBL4757761
10.02EC500.095nMCHEMBL4760781
9.99EC500.103nMCHEMBL4749385
9.97EC500.108nMT091317
9.76EC500.174nMCHEMBL4755317
9.67EC500.212nMLXR-623
9.64EC500.228nMCHEMBL59030
9.55EC500.281nMCHEMBL4762546
9.47EC500.341nMCHEMBL4757158
9.43EC500.369nMCHEMBL4764539
9.37EC500.43nMCHEMBL4777240
9.35EC500.445nMCHEMBL4781683
9.32EC500.48nMCHEMBL3360966
9.32EC500.474nMCHEMBL4748480
9.22IC500.6nMCHEMBL3814006
9.22EC500.6nMBMS-852927
9.20EC500.632nMCHEMBL4791199
9.17EC500.68nMCHEMBL4780872
9.04EC500.905nMCHEMBL4762542
9.00Ki1nMCHEMBL3360974
9.00IC501nMCHEMBL555373
9.00EC501nMCHEMBL555373
9.00IC501nMCHEMBL365544
9.00EC501nMCHEMBL365544
9.00EC501nMCHEMBL3814006
9.00Ki1nMCHEMBL3814153
9.00Ki1nMCHEMBL3814501
9.00Ki1nMCHEMBL3905741
9.00EC501nMCHEMBL3917300
9.00Ki1nMCHEMBL4756418
9.00EC501nMACETYL PODOCARPIC ACID ANHYDRIDE
9.00Ki1nMCHEMBL5955233
9.00Ki1nMCHEMBL5799423
9.00Ki1nMCHEMBL5930456
9.00Ki1nMCHEMBL6004241
9.00IC501nMCHEMBL595689
9.00EC501nMCHEMBL1093554
8.92EC501.2nMBMS-779788
8.89Ki1.3nMCHEMBL3814006
8.89Ki1.3nMCHEMBL3814206
8.85IC501.4nMCHEMBL225936
8.85IC501.4nMCHEMBL226049
8.82IC501.5nMCHEMBL1098401
8.80EC501.589nMCHEMBL4759393

PubChem BioAssay actives

1671 with measured affinity, of 3792 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’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec50<0.0001uM
(2’R,3R)-1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec50<0.0001uM
(2’S,3S)-1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
tert-butyl 2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
tert-butyl (2’R,3R)-2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
tert-butyl 2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
tert-butyl (2’R,3R)-2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta 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)benzenesulfonamide1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0001uM
tert-butyl 2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0002uM
2-[(2-chloro-4-fluorophenyl)methyl]-3-(4-fluorophenyl)-7-(trifluoromethyl)indazole1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0002uM
2-[3-[3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0002uM
tert-butyl 2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta 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’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0003uM
tert-butyl (2’S,3S)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0004uM
tert-butyl (2’R,3R)-2’-[3-[3-chloro-4-(dimethylcarbamoyl)phenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0004uM
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)phenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0004uM
tert-butyl (2’S,3S)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0005uM
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’S,3S)-2-oxo-2’-(3-phenylphenyl)spiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0006uM
N-benzyl-N-[[5-[4-(hydroxymethyl)-3-methylsulfonylphenyl]thiophen-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide1304656: Binding to human LXRbeta by radioligand displacement assayic500.0006uM
2-[2-[2-(2,6-dichlorophenyl)propan-2-yl]-1-[2-fluoro-4-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]imidazol-4-yl]propan-2-ol1328894: Agonist activity at LXR-beta in human HeLa cells assessed as induction of ABCA1 by beta-galactosidase/luciferase reporter gene assayec500.0006uM
tert-butyl (2’R,3R)-2’-[3-(3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0007uM
tert-butyl (2’S,3S)-2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0009uM
5-chloro-2-[(2R)-4-(4-fluoro-3-methylsulfonylphenyl)-2-propan-2-ylpiperazin-1-yl]-4-(trifluoromethyl)pyrimidine1304664: Displacement of [3H]TO901317 from LXRbeta ligand binding domain (unknown origin) after 30 mins by liquid scintillation countingki0.0010uM
2-[(2R)-4-(4-fluoro-3-methylsulfonylphenyl)-2-propan-2-ylpiperazin-1-yl]-4-(trifluoromethyl)pyrimidine1304664: Displacement of [3H]TO901317 from LXRbeta ligand binding domain (unknown origin) after 30 mins by liquid scintillation countingki0.0010uM
(6R)-5-(5-fluoro-6-methoxypyrimidin-4-yl)-2-(3-methylsulfonylphenyl)-6-propan-2-yl-4,6-dihydropyrrolo[3,4-c]pyrazole1316521: Displacement of radiolabeled T0901317 from LXRbeta LBD (unknown origin)ki0.0010uM
3-methyl-4-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline452959: Displacement of [3H]TO901317 from human recombinant LXRbeta expressed in Escherichia coli by flashplate methodic500.0010uM
[(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-carboxylate240148: Effective concentration against liver X receptor-beta 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-carboxamide240210: Effective concentration for cofactor association with recombinant liver X receptor-betaec500.0010uM
N-[(2-chloro-6-fluorophenyl)methyl]-N-[[4-(3-methylsulfonylphenyl)phenyl]methyl]benzenesulfonamide474686: Agonist activity at LXRbeta ligand binding domain-mediated transcriptional activity in african green monkey CV1 cells co-transfected with Gal4-SRC1 by luciferase reporter assayec500.0010uM
2-[2-[2-(2-chloro-6-fluorophenyl)propan-2-yl]-1-[2-fluoro-4-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]imidazol-4-yl]propan-2-ol1328894: Agonist activity at LXR-beta in human HeLa cells assessed as induction of ABCA1 by beta-galactosidase/luciferase reporter gene assayec500.0010uM
2-[2-[(2-chlorophenyl)methyl]-1-[4-(3-methylsulfonylphenyl)phenyl]imidazol-4-yl]propan-2-ol1172001: Binding affinity to LXRbeta-RXRalpha heterodimer (unknown origin) expressed in insect cells by scintillation proximity assayki0.0010uM
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
[4-[(3R)-4-[5-(hydroxymethyl)-4-(trifluoromethyl)pyrimidin-2-yl]-3-propan-2-ylpiperazin-1-yl]-2-methylsulfonylphenyl]methanol1562690: Binding affinity to recombinant human LXRbeta-LBD expressed in Escherichia coli BL21 (DE3) assessed as inhibitory constant incubated for 30 mins by fluorescence polarization binding assayki0.0013uM
2-[4-[[3-(3-benzyl-8-chloroquinolin-4-yl)anilino]methyl]phenyl]acetic acid1797934: LXR Binding Assay from Article 10.1016/j.bmc.2007.03.013: “Further modification on phenyl acetic acid based quinolines as liver X receptor modulators.”ic500.0014uM
2-[4-[[3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]anilino]methyl]phenyl]acetamide1797934: LXR Binding Assay from Article 10.1016/j.bmc.2007.03.013: “Further modification on phenyl acetic acid based quinolines as liver X receptor modulators.”ic500.0014uM
3-benzyl-4-[3-(3-methylsulfonylphenyl)phenyl]-8-(trifluoromethyl)quinoline478580: Displacement of [3H]T0901317 from LXRbeta ligand binding domainic500.0015uM
tert-butyl 2-oxo-2’-(3-phenylphenyl)spiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assayec500.0016uM
4-[3-(4-fluoro-3-methylsulfonylphenyl)phenyl]-3-methyl-8-(trifluoromethyl)quinoline478580: Displacement of [3H]T0901317 from LXRbeta ligand binding domainic500.0017uM
3-methyl-4-[3-(3-methylsulfonylphenyl)phenyl]-8-(trifluoromethyl)quinoline478580: Displacement of [3H]T0901317 from LXRbeta ligand binding domainic500.0018uM
2-[4-[[3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]anilino]methyl]phenyl]acetic acid1797933: LXR Binding Assay and hLXR beta Reporter Assay from Article 10.1021/jm0609566: “Discovery of phenyl acetic acid substituted quinolines as novel liver X receptor agonists for the treatment of atherosclerosis.”ic500.0019uM
[3-[3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy]phenyl]-morpholin-4-ylmethanone1799291: LXR Binding Assay and hLXR Reporter Assay from Article 10.1016/j.bmc.2008.12.048: “Biarylether amide quinolines as liver X receptor agonists.”ic500.0019uM
2-[4-[[3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy]methyl]phenyl]acetic acid1798629: LXR Binding Assay and hLXR Reporter Assay from Article 10.1021/jm800799q: “Indazole-Based Liver X Receptor (LXR) Modulators with Maintained Atherosclerotic Lesion Reduction Activity but Diminished Stimulation of Hepatic Triglyceride Synthesis”ic500.0020uM
2-[3-chloro-4-[ethyl(1,3-thiazol-4-ylmethyl)amino]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol271505: Binding affinity to LXRbeta by radioligand displacement assayic500.0020uM
3-benzyl-4-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline451979: Displacement of [3H]T0901317 from human recombinant LXRbeta-LBDic500.0020uM
ethyl 4-[3-(3-methylsulfonylphenoxy)phenyl]-8-(trifluoromethyl)quinoline-3-carboxylate452959: Displacement of [3H]TO901317 from human recombinant LXRbeta expressed in Escherichia coli by flashplate methodic500.0020uM
2-[4-[[3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl]methylamino]-2,5-dimethylphenyl]acetic acid313446: Binding affinity at human LXRbetaic500.0020uM
2-[4-[[3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl]methylamino]naphthalen-1-yl]acetic acid313446: Binding affinity at human LXRbetaic500.0020uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
T0901317decreases reaction, increases activity, increases abundance, affects binding, increases reaction (+1 more)7
triphenyl phosphatedecreases reaction, increases abundance, increases activity, affects expression2
sodium arseniteincreases expression, affects cotreatment, increases abundance2
Arsenicincreases methylation, affects cotreatment, increases abundance, increases expression2
Estradioldecreases expression2
Tobacco Smoke Pollutionincreases expression, increases methylation2
SR9238decreases reaction, increases activity1
22-hydroxycholesterolaffects cotreatment, affects localization1
bisphenol Adecreases expression1
trichostatin Aaffects expression1
beta-lapachoneincreases expression1
mono-(2-ethylhexyl)phthalateaffects binding, increases activity, increases reaction1
2-ethylhexyldiphenylphosphatedecreases reaction, increases activity, increases abundance1
manganese chlorideaffects cotreatment, increases abundance, increases expression1
loliolideincreases degradation, increases ubiquitination, decreases expression1
iron(II)-ascorbic acid complexdecreases expression, decreases reaction1
nefazodoneaffects cotreatment, increases expression1
di-n-butylphosphoric acidaffects expression1
pinoresinoldecreases expression, increases degradation, increases ubiquitination1
U 0126decreases expression, decreases reaction1
K 7174increases expression1
GW 501516increases expression1
monoisononylphthalateaffects binding, increases activity, increases reaction1
GW 3965decreases expression, decreases reaction, increases expression, affects cotreatment1
LY 518674increases expression1
abrineincreases expression1
GSK 3987increases activity, affects binding1
fatostatinincreases expression1
Ezetimibedecreases expression1
Temozolomidedecreases expression1

ChEMBL screening assays

564 unique, capped per target: 444 binding, 102 functional, 10 admet, 7 toxicity, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3377013BindingBinding affinity to LXRbeta-RXRalpha heterodimer (unknown origin) expressed in insect cells by scintillation proximity assayLiver X receptor (LXR) partial agonists: biaryl pyrazoles and imidazoles displaying a preference for LXRβ. — Bioorg Med Chem Lett
CHEMBL1047700FunctionalAgonist activity at human recombinant LXR-LBD by Gal4beta transactivation assay4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists. — Bioorg Med Chem Lett
CHEMBL4363804ADMETAgonist activity at LXR in human HepG2 cells assessed as increase in sREBP-1c mRNA expression at 10 uM incubated for 24 hrs by qPCR analysisDiscovery of tissue selective liver X receptor agonists for the treatment of atherosclerosis without causing hepatic lipogenesis. — Eur J Med Chem

Cellosaurus cell lines

10 cell lines: 3 embryonic stem cell, 3 cancer cell line, 3 transformed cell line, 1 spontaneously immortalized cell line

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

CellosaurusNameCategorySex
CVCL_A4T0SEES3-1V human NR1H2, clone1Embryonic stem cellMale
CVCL_A4T1SEES3-1V human NR1H2, clone2Embryonic stem cellMale
CVCL_A4T2SEES3-1V human NR1H2, clone3Embryonic stem cellMale
CVCL_B1GMAbcam A-549 NR1H2 KOCancer cell lineMale
CVCL_D7H3Ubigene HEK293T NR1H2 KOTransformed cell lineFemale
CVCL_E2EJHAP1 NR1H2 (-) 1Cancer cell lineMale
CVCL_E2EKHAP1 NR1H2 (-) 2Cancer cell lineMale
CVCL_KX93PathHunter CHO-K1 LXRbeta Protein InteractionSpontaneously immortalized cell lineFemale
CVCL_KZ59PathHunter HEK 293 LXRbeta-NCoR1 Protein InteractionTransformed cell lineFemale
CVCL_LF46GeneBLAzer LXRbeta-UAS-bla HEK 293TTransformed cell lineFemale

Clinical trials (associated diseases)

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

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
v1.1.4
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