ESR2

Summary

ESR2 (estrogen receptor 2, HGNC:3468) is a protein-coding gene on chromosome 14q23.2-q23.3, encoding Estrogen receptor beta (Q92731). Nuclear hormone receptor.

This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized.

Source: NCBI Gene 2100 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ovarian dysgenesis 8 (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 199 total — 1 pathogenic
• Phenotypes (HPO): 10
• Druggable target: yes — 44 molecules with ChEMBL bioactivity
• Transcription factor: yes — 223 downstream targets (CollecTRI)
• MANE Select transcript: NM_001437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3468
Approved symbol	ESR2
Name	estrogen receptor 2
Location	14q23.2-q23.3
Locus type	gene with protein product
Status	Approved
Aliases	NR3A2, Erb, ER-beta
Ensembl gene	ENSG00000140009
Ensembl biotype	protein_coding
OMIM	601663
Entrez	2100

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000267525, ENST00000341099, ENST00000344288, ENST00000353772, ENST00000358599, ENST00000553796, ENST00000554520, ENST00000554572, ENST00000555278, ENST00000555483, ENST00000555783, ENST00000556275, ENST00000557772

RefSeq mRNA: 7 — MANE Select: NM_001437 NM_001040275, NM_001214902, NM_001271876, NM_001271877, NM_001291712, NM_001291723, NM_001437

CCDS: CCDS32096, CCDS55920, CCDS61469, CCDS61470, CCDS9762

Canonical transcript exons

ENST00000341099 — 9 exons

Exon	Start	End
ENSE00001193559	64282624	64283075
ENSE00001564600	64228317	64233323
ENSE00001848078	64294033	64294371
ENSE00003490667	64268795	64268911
ENSE00003514177	64249546	64249679
ENSE00003539676	64260449	64260748
ENSE00003611076	64257226	64257364
ENSE00003650176	64279981	64280153
ENSE00003765881	64234970	64235150

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 78.65.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5672 / max 36.0868, expressed in 255 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143618	0.2212	112
143614	0.1321	49
143612	0.0913	44
143617	0.0458	5
143613	0.0385	19
143616	0.0218	7
143615	0.0166	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	78.65	gold quality
right adrenal gland cortex	UBERON:0035827	78.62	gold quality
left adrenal gland	UBERON:0001234	77.75	gold quality
left adrenal gland cortex	UBERON:0035825	76.91	gold quality
secondary oocyte	CL:0000655	75.50	gold quality
adrenal cortex	UBERON:0001235	75.50	gold quality
adrenal gland	UBERON:0002369	74.84	gold quality
sperm	CL:0000019	74.42	silver quality
left ovary	UBERON:0002119	74.35	gold quality
right ovary	UBERON:0002118	72.94	gold quality
male germ cell	CL:0000015	72.45	silver quality
granulocyte	CL:0000094	72.44	gold quality
colonic epithelium	UBERON:0000397	71.23	gold quality
ovary	UBERON:0000992	71.03	gold quality
left testis	UBERON:0004533	70.30	gold quality
metanephros cortex	UBERON:0010533	70.23	gold quality
right testis	UBERON:0004534	69.29	gold quality
testis	UBERON:0000473	69.04	gold quality
endothelial cell	CL:0000115	68.03	gold quality
buccal mucosa cell	CL:0002336	68.03	silver quality
lower esophagus mucosa	UBERON:0035834	67.88	gold quality
spleen	UBERON:0002106	66.31	gold quality
gastrocnemius	UBERON:0001388	66.29	gold quality
lymph node	UBERON:0000029	66.26	gold quality
bone marrow cell	CL:0002092	66.25	silver quality
hindlimb stylopod muscle	UBERON:0004252	66.14	gold quality
adrenal tissue	UBERON:0018303	65.40	gold quality
muscle of leg	UBERON:0001383	65.33	gold quality
tendon of biceps brachii	UBERON:0008188	64.87	silver quality
Brodmann (1909) area 10	UBERON:0013541	64.69	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	48.46
E-ANND-3	no	5.28
E-ENAD-27	no	3.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

223 targets.

Target	Regulation
ABCB1
ABCG2
ACP3	Unknown
ADAM2
ADIPOQ
ADORA1
AHR
AKT1
AMH	Repression
AP1	Unknown
APP
AQP3
AR
ARHGDIA
ATP7A
AVP	Unknown
B3GAT3
BCL2	Unknown
BCL9
BIRC5	Repression
BMP10
BMP2
BMP6
BRCA2	Repression
BTG2	Repression
C3	Unknown
CAPN2
CAT
CAV1	Unknown
CCAR2

JASPAR motifs

Motif	Name	Family
MA0258.1	ESR2	Steroid hormone receptors (NR3)
MA0258.2	ESR2	Steroid hormone receptors (NR3)

JASPAR matrix evidence (PMIDs): PMID:18272478

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ARNT, CREB1, ESR1, ESR2, HIF1A, ID1, NCOA1, NFATC4, NR0B2, PGR, PITX2, SP1, SPI1, STAT1, STAT3, STAT5A, STAT5B, TBX15, TFAP2A

miRNA regulators (miRDB)

19 targeting ESR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-5704	94.82	67.46	448

Literature-anchored findings (GeneRIF, showing 40)

• ERa but not ERbeta is present in human preadipocytes (PMID:11720251)
• To determine whether receptor-induced changes in DNA structure are related to transactivation, we compared the abilities of ER alpha and ER beta to activate transcription and induce distortion and bending in DNA. (PMID:11773069)
• Homology modeling of the estrogen receptor subtype beta (ER-beta) and calculation of ligand binding affinities. (PMID:11775002)
• Estrogen receptors are found in brain areas involved in regulation of food intake. The anorexic effects of estrogen are accentuated by stress, thus that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. (PMID:11803451)
• expression of estrogen receptor alpha and estrogen receptor beta were studied in leiomyomas and homologous myometrium from women in the proliferative phase of the menstrual cycle and from women treated with a gonadotropin-releasing hormone analogue (PMID:11826769)
• these results show that although estrogen can up-regulate endogenous PR gene expression in osteoblasts via both ER isoforms, ER-alpha is the predominant inducer. (PMID:11918216)
• the extent of AF-2-dependent cofactor recruitment by ERalpha or ERbeta is affected both by ER ligands and estrogen-responsive element sequences (PMID:11923465)
• crystal structures of the ER alpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ER beta LBD bound to THC (PMID:11953755)
• Identification of ten exon deleted ERbeta mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor beta mRNA is distinct from that of estrogen receptor alpha. (PMID:11959119)
• demonstrated that ERalpha but not ERbeta directly interacts with calmodulin (PMID:11981030)
• effect on cyclin D1 expression (PMID:11986316)
• ER-beta is the only estrogen receptor detected at the protein level in the morphologically normal developing human fetal prostate (PMID:11992621)
• estrogen via estrogen receptor 2 directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast (PMID:12021200)
• expressed in human stomach adenocarcinoma (PMID:12073050)
• We outline additional exons in the genes’ 5’- and 3’-untranslated regions and a nested gene. (PMID:12111450)
• Expression and cellular localization of naturally occurring beta estrogen receptors in uterine and mammary cell lines (PMID:12112024)
• The dominant expression of ER-beta in cultured female skin fibroblasts suggests that ER-beta may play a dominant role in collaboration with ER-alpha in the regulation of estrogen action in skin. (PMID:12119550)
• lack of effect of RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis (PMID:12137804)
• ER beta gene polymorphisms are associated with higher bone mineral density in premenopausal women, suggesting that the ER beta gene may have a modulatory role in bone metabolism in young adulthood. (PMID:12151079)
• Estrogen receptor-beta is expressed in Barrett’s metaplasia and associated adenocarcinoma of the esophagus. (PMID:12168823)
• ERalpha and ERbeta make unique contributions to xenoestrogen action in target cells (PMID:12200415)
• Estrogen receptor-beta is present in the human growth plate in childhood and adolescence (PMID:12207170)
• expression of either ERalpha or beta lowers both basal and stimulated PPARgamma-mediated transactivation, demonstrating that signal cross talk exists bidirectionally between PPARgamma and ER in breast cancer cells (PMID:12242035)
• estradiol receptor beta1 and estradiol receptor betacx/beta2 proteins were identified within multiple cell types within the endometrium throughout the menstrual cycle with levels of ERbetacx/beta2 reduced in the midsecretory phase (PMID:12414901)
• data indicate that coordinated expression of ERalpha and ERbeta might be necessary for normal estrogen action in myometrium and that estrogen appears a dominant regulator of both receptors in the myometrium (PMID:12475719)
• Data show that normal breast tissues express 9 of the 10 identified variant estrogen receptor beta mRNAs, and of the nine variants, mRNAs with exons 5-6 deletions were significantly decreased in a large majority of cancer tissues. (PMID:12477483)
• Data report the cloning of a novel isoform of the ERbeta cDNA that consists of a previously unidentified 5’-sequence and the exons 5-8 of the ERbeta gene. (PMID:12477486)
• continuous expression of ERbeta at significant levels in untreated primary and metastatic adenocarcinoma indicates these tumors can use estrogens through an ERbeta-mediated pathway (PMID:12497580)
• During the second trimester, some but not all somatic cells within the human fetal testis express wild-type ER-beta (ER-beta-1) protein and/or the variant isoform of ER-beta (ER-beta-2) that lacks amino acids essential for binding to estradiol. (PMID:12519886)
• Ligands differentially modulate the protein interactions of the human estrogen receptors alpha and beta (PMID:12547192)
• a single residue in the ligand-binding domain determines the stereoselectivity of ERbeta (PMID:12547836)
• Data show that liganded ERalpha is a much more potent transcriptional activator than ERbeta with chromatin templates, but not with naked DNA. (PMID:12554660)
• Our findings highlight that a limited number of critical interactions of DPN with the ERbeta ligand-binding pocket underlie its ER subtype-selective character. (PMID:12554752)
• Mechanistic differences in the activation of estrogen receptor-alpha (ER alpha)- and rhis protein’s dependent gene expression by cAMP signaling pathway(s). (PMID:12566449)
• This protein is expressed and synthesized in the human internal thoracic artery. (PMID:12597128)
• analysis of isoforms of estrogen receptor beta (PMID:12650698)
• modulates synthesis of bone matrix proteins in osteoblast-like MG63 cells (PMID:12682916)
• The wide distribution of ERbeta in human skin suggests that oestrogens may play an important role in the maintenance of skin and in the regulation of the pilosebaceous unit, and provides further evidence for oestrogen action in non-classic target tissues. (PMID:12702147)
• ER-beta E5DV, E6DV and E5+6DV, constitutively expressed in human ovary and uterine endometrium might, in part regulate estrogen responsiveness (PMID:12710996)
• study of equilibrium dissociation constants for dimerization of ERbeta (PMID:12710997)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	esr2a	ENSDARG00000016454
danio_rerio	esr2b	ENSDARG00000034181
mus_musculus	Esr2	ENSMUSG00000021055
rattus_norvegicus	Esr2	ENSRNOG00000005343
drosophila_melanogaster	ERR	FBGN0035849

Paralogs (8): PGR (ENSG00000082175), ESR1 (ENSG00000091831), NR3C1 (ENSG00000113580), ESRRB (ENSG00000119715), NR3C2 (ENSG00000151623), AR (ENSG00000169083), ESRRA (ENSG00000173153), ESRRG (ENSG00000196482)

Protein

Protein identifiers

Estrogen receptor beta — Q92731 (reviewed: Q92731)

Alternative names: Nuclear receptor subfamily 3 group A member 2

All UniProt accessions (5): Q92731, A0A348FV93, F1D8N3, G3V5S2, Q7LCB3

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Lacks ligand binding ability and has no or only very low ERE binding activity resulting in the loss of ligand-dependent transactivation ability.

Subunit / interactions. Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA1, NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with UBE1C. Interacts with AKAP13. Interacts with DNTTIP2. Interacts with isoform 4 of TXNRD1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes, including cyclin-D1/CCND1 AP-1 promoter. Interacts with DNAAF4. Interacts with PRMT2. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with RBM39, in the presence of estradiol (E2). Interacts with STUB1/CHIP. Preferentially forms a heterodimer with ESR1 rather than ESR2 isoform 1 and inhibits DNA-binding by ESR1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, but not in colon and liver tumors. Expressed in spleen, thymus, testis and ovary and at a lower level in skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland and uterus. Expressed in the testis. Expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus. Expressed in testis, placenta, skeletal muscle, spleen and leukocytes, and at a lower level in heart, lung, liver, kidney, pancreas, thymus, prostate, colon, small intestine, bone marrow, mammary gland and uterus. Not expressed in brain.

Post-translational modifications. Phosphorylation at Ser-87 and Ser-105 recruits NCOA1.

Disease relevance. Ovarian dysgenesis 8 (ODG8) [MIM:618187] An autosomal dominant form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Does not form homodimers. Does not form homodimers.

Similarity. Belongs to the nuclear hormone receptor family. NR3 subfamily.

Isoforms (9)

UniProt ID	Names	Canonical?
Q92731-1	1, Beta-1	yes
Q92731-2	2, Beta-2, CX
Q92731-3	3, Beta-2A
Q92731-4	4, Beta-3
Q92731-5	5, Beta-4
Q92731-6	6, Beta-5
Q92731-7	7, Beta-5A
Q92731-8	8, Beta-6
Q92731-9	9

RefSeq proteins (7): NP_001035365, NP_001201831, NP_001258805, NP_001258806, NP_001278641, NP_001278652, NP_001428* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR021064	ER-beta-like_N	Domain
IPR024178	Est_rcpt/est-rel_rcp	Family
IPR028355	ER-beta/gamma	Family
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050200	Nuclear_hormone_rcpt_NR3	Family

Pfam: PF00104, PF00105, PF12497

UniProt features (50 total): helix 15, splice variant 11, strand 6, sequence variant 4, mutagenesis site 4, zinc finger region 2, region of interest 2, modified residue 2, chain 1, domain 1, DNA-binding region 1, turn 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3OLL	X-RAY DIFFRACTION	1.5
7XVY	X-RAY DIFFRACTION	1.54
1QKM	X-RAY DIFFRACTION	1.8
7XWQ	X-RAY DIFFRACTION	1.89
7XWP	X-RAY DIFFRACTION	1.92
2YJD	X-RAY DIFFRACTION	1.93
3OMQ	X-RAY DIFFRACTION	1.97
9ECF	X-RAY DIFFRACTION	2
1YYE	X-RAY DIFFRACTION	2.03
3OMP	X-RAY DIFFRACTION	2.05
7XVZ	X-RAY DIFFRACTION	2.08
2NV7	X-RAY DIFFRACTION	2.1
4J24	X-RAY DIFFRACTION	2.1
4ZI1	X-RAY DIFFRACTION	2.1
7XWR	X-RAY DIFFRACTION	2.16
1X76	X-RAY DIFFRACTION	2.2
1ZAF	X-RAY DIFFRACTION	2.2
2FSZ	X-RAY DIFFRACTION	2.2
2GIU	X-RAY DIFFRACTION	2.2
3OLS	X-RAY DIFFRACTION	2.2
9EBL	X-RAY DIFFRACTION	2.2
1U3R	X-RAY DIFFRACTION	2.21
3OMO	X-RAY DIFFRACTION	2.21
2JJ3	X-RAY DIFFRACTION	2.28
1X78	X-RAY DIFFRACTION	2.3
1X7B	X-RAY DIFFRACTION	2.3
1X7J	X-RAY DIFFRACTION	2.3
4J26	X-RAY DIFFRACTION	2.3
2Z4B	X-RAY DIFFRACTION	2.34
1U3Q	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92731-F1	69.76	0.46

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): 87, 105

Mutagenesis-validated functional residues (4):

Position	Phenotype
87	enhances repression by activated erbb2/erbb3; when associated with a-105.
87	abolishes repression by activated erbb2/erbb3; when associated with d-105.
105	enhances repression by activated erbb2/erbb3; when associated with a-87.
105	abolishes repression by activated erbb2/erbb3; when associated with d-87.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8939211	ESR-mediated signaling
R-HSA-9009391	Extra-nuclear estrogen signaling

MSigDB gene sets: 222 (showing top): GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELLULAR_RESPONSE_TO_LIPID, LI_PROSTATE_CANCER_EPIGENETIC, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MODULE_404, GOBP_CELL_CELL_SIGNALING, PID_ERB_GENOMIC_PATHWAY, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, CCANNAGRKGGC_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, USF_01, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), negative regulation of cell growth (GO:0030308), estrogen receptor signaling pathway (GO:0030520), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), cellular response to estradiol stimulus (GO:0071392), cellular response to oxygen-containing compound (GO:1901701)

GO Molecular Function (16): 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 (GO:0003677), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), steroid binding (GO:0005496), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), nuclear estrogen receptor activity (GO:0030284), estrogen response element binding (GO:0034056), receptor antagonist activity (GO:0048019), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), lipid binding (GO:0008289), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Generic Transcription Pathway	1
Negative regulation of the PI3K/AKT network	1
Signaling by Nuclear Receptors	1
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
DNA-templated transcription	2
cell communication	2
signaling	2
nuclear receptor-mediated steroid hormone signaling pathway	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
binding	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
response to estradiol	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
cellular response to chemical stimulus	1
response to oxygen-containing compound	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
nuclear receptor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
lipid binding	1
transition metal ion binding	1
protein binding	1

Protein interactions and networks

STRING

3274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESR2	NCOA1	Q15788	946
ESR2	CAV1	Q03135	945
ESR2	GPER1	Q99527	943
ESR2	ESR1	P03372	934
ESR2	CYP19A1	P11511	923
ESR2	SRC	P12931	889
ESR2	NCOA2	Q15596	872
ESR2	KLF5	Q13887	835
ESR2	NCOA3	Q9Y6Q9	817
ESR2	IGF1R	P08069	807
ESR2	ATP5PF	P18859	803
ESR2	OXTR	P30559	791
ESR2	SP1	P08047	786
ESR2	GNRH1	P01148	785
ESR2	NCOA7	Q8NI08	785

IntAct

86 interactions, top by confidence:

A	B	Type	Score
CCN2	ESR1	psi-mi:“MI:0914”(association)	0.680
ESR2	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	ESR2	psi-mi:“MI:0915”(physical association)	0.670
ESR2	ESR2	psi-mi:“MI:2364”(proximity)	0.670
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
ESR2	CCN2	psi-mi:“MI:0915”(physical association)	0.630
ESR2	CCN2	psi-mi:“MI:0407”(direct interaction)	0.630
	ESR2	psi-mi:“MI:0407”(direct interaction)	0.610
ESR2		psi-mi:“MI:0407”(direct interaction)	0.610
	ESR2	psi-mi:“MI:0915”(physical association)	0.610
FOXO3	ESR2	psi-mi:“MI:0915”(physical association)	0.590
ESR2	PPP5C	psi-mi:“MI:0915”(physical association)	0.510
PPP5C	ESR2	psi-mi:“MI:0915”(physical association)	0.510
ESR2	Ncor1	psi-mi:“MI:0915”(physical association)	0.510
ESR2		psi-mi:“MI:0914”(association)	0.500

BioGRID (2564): PLSCR1 (Two-hybrid), UBE3A (Affinity Capture-Western), PSMC5 (Two-hybrid), NCOA1 (Two-hybrid), AGR3 (Two-hybrid), CASC3 (Two-hybrid), CASZ1 (Two-hybrid), DKK3 (Two-hybrid), FAM84B (Two-hybrid), IL13RA2 (Two-hybrid), IL24 (Two-hybrid), ITIH5 (Two-hybrid), KLK9 (Two-hybrid), MRC2 (Two-hybrid), TFF1 (Two-hybrid)

ESM2 similar proteins: A0A072VIM5, A0A0K0PU92, A2CIR7, F4IG73, G3LSH3, G8GTN7, O42132, P03372, P06211, P0CI65, P19785, P49884, P50241, P50242, P57717, P57753, Q29040, Q2HW56, Q2QXZ2, Q2RAQ5, Q337A0, Q53AD2, Q5D0W8, Q5YLM1, Q6KAE5, Q6NLQ8, Q6PJI9, Q6WQJ1, Q7EZ44, Q7Z494, Q8C0M0, Q8CFE5, Q8IPH9, Q8IZ41, Q92731, Q9BZ72, Q9FDY4, Q9IAK1, Q9M1I7, Q9P203

Diamond homologs: A0JNE3, A2T7D9, A3RGC1, G5EFF5, O02151, O08537, O09017, O13124, O18531, O35627, O42132, O42392, O44960, O45436, O45666, O54915, O62389, O75469, P10588, P11473, P13053, P13054, P13056, P15370, P16376, P18515, P33242, P33244, P37234, P41829, P41830, P43136, P48281, P49116, P49117, P49701, P49867, P49883, P50241, P50242

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
17beta-estradiol	up-regulates	ESR2	“chemical activation”
dutasteride	up-regulates	ESR2	“chemical activation”
ESR2	“up-regulates quantity by expression”	TFF1	“transcriptional regulation”
ESR2	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
ESR2	“up-regulates quantity by expression”	TGFA	“transcriptional regulation”
tamoxifen	“down-regulates activity”	ESR2	“chemical inhibition”
estramustine	“up-regulates activity”	ESR2	“chemical activation”
“tamoxifen citrate”	“down-regulates activity”	ESR2	“chemical inhibition”
fulvestrant	“down-regulates activity”	ESR2	“chemical inhibition”
ESR2	“up-regulates quantity by expression”	OXT	“transcriptional regulation”
ESR2	“up-regulates quantity by expression”	CRH	“transcriptional regulation”
ESR1	up-regulates	ESR2	binding
NR0B2	“down-regulates quantity by repression”	ESR2	“transcriptional regulation”
ESR2	“down-regulates quantity by repression”	SCN1A	“transcriptional regulation”
ESR2	“down-regulates quantity by repression”	SCN9A	“transcriptional regulation”
ESR2	“down-regulates quantity by repression”	SCN10A	“transcriptional regulation”
ESR2	“down-regulates quantity by repression”	SCN11A	“transcriptional regulation”
estrone	“up-regulates activity”	ESR2	“chemical activation”
estriol	“up-regulates activity”	ESR2	“chemical activation”
17beta-estradiol	“up-regulates activity”	ESR2	“chemical activation”
afimoxifene	“down-regulates activity”	ESR2	“chemical inhibition”
diethylstilbestrol	“up-regulates activity”	ESR2	“chemical activation”
genistein	“up-regulates activity”	ESR2	“chemical activation”
“bisphenol A”	“up-regulates activity”	ESR2	“chemical activation”
biphenyl-4,4’-diol	“up-regulates activity”	ESR2	“chemical activation”
“perfluorooctane-1-sulfonic acid”	“up-regulates activity”	ESR2	“chemical activation”
“perfluorohexanesulfonic acid”	“up-regulates activity”	ESR2	“chemical activation”
“perfluorooctanoic acid”	“up-regulates activity”	ESR2	“chemical activation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	104
Likely benign	49
Benign	35

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
590785	NM_001437.3(ESR2):c.941A>G (p.Lys314Arg)	Pathogenic

SpliceAI

10470 predictions. Top by Δscore:

Variant	Effect	Δscore
14:64087654:A:AG	acceptor_gain	1.0000
14:64087654:ATTCT:A	acceptor_gain	1.0000
14:64087655:T:G	acceptor_gain	1.0000
14:64087658:T:TA	acceptor_gain	1.0000
14:64087660:T:TA	acceptor_gain	1.0000
14:64087666:T:G	acceptor_gain	1.0000
14:64087666:TCTA:T	acceptor_loss	1.0000
14:64087667:CTAG:C	acceptor_loss	1.0000
14:64087669:A:AG	acceptor_gain	1.0000
14:64087669:A:G	acceptor_loss	1.0000
14:64087669:AGAT:A	acceptor_gain	1.0000
14:64087669:AGATG:A	acceptor_gain	1.0000
14:64087670:G:A	acceptor_loss	1.0000
14:64087670:G:GT	acceptor_gain	1.0000
14:64087670:GA:G	acceptor_gain	1.0000
14:64087670:GAT:G	acceptor_gain	1.0000
14:64087670:GATG:G	acceptor_gain	1.0000
14:64087670:GATGG:G	acceptor_gain	1.0000
14:64087785:T:G	donor_gain	1.0000
14:64087852:CTGAT:C	donor_gain	1.0000
14:64087853:TGAT:T	donor_gain	1.0000
14:64087854:GAT:G	donor_gain	1.0000
14:64087854:GATG:G	donor_gain	1.0000
14:64087855:AT:A	donor_gain	1.0000
14:64087856:TG:T	donor_loss	1.0000
14:64087857:G:GG	donor_gain	1.0000
14:64087857:GTA:G	donor_loss	1.0000
14:64087858:TAAG:T	donor_loss	1.0000
14:64089571:TAGG:T	acceptor_loss	1.0000
14:64089572:A:AG	acceptor_gain	1.0000

AlphaMissense

3493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:64268805:C:A	M214I	1.000
14:64268805:C:G	M214I	1.000
14:64268805:C:T	M214I	1.000
14:64268806:A:G	M214T	1.000
14:64268820:A:C	C209W	1.000
14:64268821:C:G	C209S	1.000
14:64268821:C:T	C209Y	1.000
14:64268822:A:G	C209R	1.000
14:64268822:A:T	C209S	1.000
14:64268830:A:G	L206P	1.000
14:64268834:G:C	R205G	1.000
14:64268835:G:C	C204W	1.000
14:64268836:C:A	C204F	1.000
14:64268836:C:G	C204S	1.000
14:64268836:C:T	C204Y	1.000
14:64268837:A:G	C204R	1.000
14:64268837:A:T	C204S	1.000
14:64268844:G:C	C201W	1.000
14:64268845:C:A	C201F	1.000
14:64268845:C:G	C201S	1.000
14:64268845:C:T	C201Y	1.000
14:64268846:A:G	C201R	1.000
14:64268846:A:T	C201S	1.000
14:64268852:T:C	K199E	1.000
14:64268855:G:T	R198S	1.000
14:64268857:C:G	R197P	1.000
14:64268874:A:C	C191W	1.000
14:64268875:C:A	C191F	1.000
14:64268875:C:G	C191S	1.000
14:64268875:C:T	C191Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000029350 (14:64305497 C>A,T), RS1000032545 (14:64228148 A>G), RS1000047363 (14:64300798 T>C), RS1000052772 (14:64235679 G>C), RS1000082748 (14:64322047 A>T), RS1000112252 (14:64333962 A>C), RS1000119735 (14:64258847 C>T), RS1000149884 (14:64252726 C>T), RS1000159731 (14:64275451 T>C), RS1000172506 (14:64259024 G>T), RS1000196446 (14:64314450 A>G), RS1000229015 (14:64314755 G>A), RS1000265107 (14:64269937 T>C), RS1000287828 (14:64286463 G>A), RS1000366722 (14:64304016 A>G)

Disease associations

OMIM: gene MIM:601663 | disease phenotypes: MIM:618187

GenCC curated gene-disease

Disease	Classification	Inheritance
ovarian dysgenesis 8	Moderate	Autosomal dominant
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive
familial medullary thyroid carcinoma	Supportive	Autosomal dominant

Mondo (3): ovarian dysgenesis 8 (MONDO:0032590), familial medullary thyroid carcinoma (MONDO:0007958), (MONDO:0018393)

Orphanet (0):

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000059	Hypoplastic labia majora
HP:0000786	Primary amenorrhea
HP:0000939	Osteoporosis
HP:0003782	Eunuchoid habitus
HP:0008214	Decreased serum estradiol
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0011969	Elevated circulating luteinizing hormone level
HP:0025708	Early young adult onset
HP:0031103	Decreased circulating antimullerian hormone circulation

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003148_4	Prostate cancer	6.000000e-10
GCST004601_173	Red blood cell count	9.000000e-10
GCST004604_61	Hematocrit	3.000000e-11
GCST004615_96	Hemoglobin concentration	5.000000e-12
GCST005839_35	Depression	8.000000e-10
GCST006414_22	Atrial fibrillation	3.000000e-31
GCST007576_163	Chronotype	6.000000e-09
GCST008595_85	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-11
GCST009391_746	Metabolite levels	1.000000e-08
GCST009600_15	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-09
GCST010083_247	Hemoglobin levels	2.000000e-23
GCST90002383_257	Hematocrit	5.000000e-30
GCST90002384_339	Hemoglobin	6.000000e-28
GCST90002403_508	Red blood cell count	5.000000e-25

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0008328	chronotype measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0010390	sphingomyelin 14:0 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536911	Familial medullary thyroid carcinoma (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093866 (PROTEIN FAMILY), CHEMBL242 (SINGLE PROTEIN), CHEMBL5465555 (PROTEIN-PROTEIN INTERACTION), CHEMBL6177909 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

44 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,061,967 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,574
CHEMBL11359	CISPLATIN	4
CHEMBL1276308	MIFEPRISTONE	4	30,535
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL1358	FULVESTRANT	4	56,655
CHEMBL328190	LASOFOXIFENE	4	10,617
CHEMBL411	DIETHYLSTILBESTROL	4	353,912
CHEMBL717	MEDROXYPROGESTERONE ACETATE	4	51,452
CHEMBL81	RALOXIFENE	4	78,049
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1200474	DEMECLOCYCLINE HYDROCHLORIDE	4	1,867
CHEMBL1230314	ESTETROL ANHYDROUS	4	1,198
CHEMBL1393	SPIRONOLACTONE	4	49,171
CHEMBL1405	ESTRONE	4	36,722
CHEMBL193482	ESTRIOL	4	21,295
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL4297509	ELACESTRANT	4	1,095
CHEMBL46740	BAZEDOXIFENE	4	5,052
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL63857	PHENOLPHTHALEIN	4
CHEMBL691	ETHINYL ESTRADIOL	4
CHEMBL786	TAMOXIFEN CITRATE	4
CHEMBL68055	ACOLBIFENE	3
CHEMBL1096979	BENSERAZIDE	3
CHEMBL195560	ISOPHENOXODIOL	3
CHEMBL226267	ARZOXIFENE	3
CHEMBL4475463	AMCENESTRANT	3
CHEMBL489	AFIMOXIFENE	3
CHEMBL11252	STALLIMYCIN	2

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10140457	Toxicity	3	letrozole	Breast Neoplasms
rs4986938	Toxicity	3	tamoxifen
rs944050	Efficacy	3	gemcitabine	Pancreatic Neoplasms

PharmGKB variants

16 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs944050	ESR2	3	2.25	1	gemcitabine
rs944459	ESR2		0.00	0
rs1152580	ESR2		0.00	0
rs1256031	ESR2		0.00	0
rs1256049	ESR2		0.00	0
rs1256061	ESR2		0.00	0
rs1256064	ESR2		0.00	0
rs1256120	ESR2		0.00	0
rs1952586	ESR2		0.00	0
rs3020445	ESR2		0.00	0
rs4986938	ESR2	3	0.75	1	tamoxifen
rs8017441	ESR2		0.00	0
rs10140457	ESR2	3	2.50	1	letrozole
rs10148269	ESR2		0.00	0
rs12435857	ESR2		0.00	0
rs17179740	ESR2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 3A. Estrogen receptors

Most potent curated ligand interactions (24 total), top 24:

Ligand	Action	Affinity	Parameter
4-hydroxytamoxifen	Antagonist	10.6	pKi
diethylstilbestrol	Agonist	9.8	pKi
17β-estradiol	Agonist	9.34	pKi
fulvestrant	Antagonist	8.86	pKi
WAY200070	Agonist	8.7	pEC50
diarylpropionitrile	Agonist	8.6	pKi
R,R-THC	Antagonist	8.44	pKi
estriol	Agonist	8.4	pKi
FERb 033	Agonist	8.32	pEC50
prinaberel	Agonist	8.3	pIC50
AC-186	Agonist	8.22	pEC50
genistein	Agonist	8.2	pKi
ethinylestradiol	Agonist	8.09	pIC50
raloxifene	Antagonist	8.0	pKi
estrone	Agonist	7.93	pKi
lasofoxifene	Partial agonist	7.89	pIC50
HPTE	Antagonist	7.64	pKi
norendoxifen	Agonist	7.56	pEC50
(S)-liquiritigenin	Agonist	7.44	pEC50
tamoxifen	Agonist	7.16	pKi
bazedoxifene	Antagonist	7.07	pIC50
PHTPP	Antagonist	6.9	pKi
ospemifene	Antagonist	6.39	pKi
bisphenol A	Partial agonist	5.96	pEC50

Binding affinities (BindingDB)

711 measured of 749 human assays (766 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-cyclohexyl-3-(1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole	EC50	0.00114 nM
2-[(2,5-dimethoxybenzylidene)amino]-4,5-bis(2-furyl)-3-furonitrile	EC50	0.00197 nM
3-(2-furanylmethyl)-2-propylthiochromeno[2,3-d]pyrimidine-4,5-dione	EC50	0.0148 nM
(8R,9S,14S,17R)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol	KI	0.025 nM	US-9561238: Pharmaceutical compositions comprising estetrol derivatives for use in cancer therapy
racemic mixture	KI	0.17 nM
(2R,6S,7R)-7-(4-hydroxyphenyl)-10-methyl-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.26 nM
(2R,6S,7R)-7-(4-hydroxyphenyl)-10-(methoxymethyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.28 nM
6-(4-fluorophenyl)-5-{4-[2-(piperidin-1-yl)ethoxy]phenoxy}naphthalen-2-ol	KI	0.3 nM
(2R,4S,6S,7R)-7-(4-hydroxyphenyl)-4-methyl-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.31 nM
(2R,4R,6S,7R)-7-(4-hydroxyphenyl)-4-(trifluoromethyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.41 nM
(2R,6S,7R)-4,4-difluoro-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.44 nM
6,8-dihydroxy-2-(4-hydroxyphenyl)-4-(4-methoxyphenyl)isoquinolin-1-one	KI	0.48 nM	US-9623021: Nuclear receptor binding agents
(2R,6S,7R)-4,4-difluoro-7-(4-hydroxyphenyl)-10-(methoxymethyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.53 nM
racemic mixture	KI	0.63 nM
9-nitro-4-phenyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-6-carboxylic acid	EC50	0.65 nM
racemic mixture	KI	0.66 nM
6-(4-hydroxyphenyl)-5-({4-[2-(piperidin-1-yl)ethoxy]phenyl}methyl)naphthalen-2-ol	KI	0.7 nM
(2R,4S,6S,7R)-7-(4-hydroxyphenyl)-4-(trifluoromethyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.7 nM
(2R,6S,7R)-10-(ethoxymethyl)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	0.745 nM
2,3-di-2-furyl-6-{[4-(2-methoxyphenyl)piperazin-1-yl]carbonyl}quinoxaline	EC50	0.87 nM
racemic mixture	KI	0.88 nM
CHEMBL5184751	IC50	1.3 nM
LY 2066948	KI	1.36 nM
(2S,6R,7S)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(13),9,11-trien-12-ol	KI	1.54 nM
6,8-dihydroxy-2-(4-hydroxyphenyl)-4-[(E)-prop-1-enyl]isoquinolin-1-one	KI	1.66 nM	US-9623021: Nuclear receptor binding agents
(1S,10R,11S,14S,15S)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2,4,6-triene-5,14-diol	IC50	1.7 nM	US-9422324: 6-substituted demethyl-estradiol derivatives as selective ER-β agonists
4-keto-4-(2-thienyl)butyric acid [2-(2-furfurylamino)-2-keto-ethyl] ester	EC50	1.74 nM
5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-1-cyclohexanol	EC50	2.14 nM
6-bromo-2-{[4-(2-furoyl)-1-piperazinyl]carbonyl}pyrazolo[1,5-a]pyrimidine	EC50	2.73 nM
4-bromo-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinolin-1-one	KI	3 nM	US-9623021: Nuclear receptor binding agents
4-chloro-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinolin-1-one	KI	3 nM	US-9623021: Nuclear receptor binding agents
6,8-dihydroxy-2-(4-hydroxyphenyl)-4-phenylisoquinolin-1-one	KI	3.03 nM	US-9623021: Nuclear receptor binding agents
4-ethenyl-2-(3-fluoro-4-hydroxyphenyl)-6,8-dihydroxyisoquinolin-1-one	KI	3.96 nM	US-9623021: Nuclear receptor binding agents
(1S,10R,11S,14R,15S)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol	EC50	4.5 nM
6-(4-methanesulfonylphenyl)-5-({4-[2-(piperidin-1-yl)ethoxy]phenyl}methyl)naphthalen-2-ol	EC50	4.78 nM
(2R,6S,7R)-10-(hydroxymethyl)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol	KI	5.97 nM
4-bromo-6-hydroxy-2-(4-hydroxyphenyl)-1-oxoisoquinoline-8-carbonitrile	KI	6 nM	US-9623021: Nuclear receptor binding agents
4-[N-[(2,3-dimethylphenyl)methyl]-4-hydroxyanilino]phenol	KI	6.44 nM	US-8546451: Estrogen receptor ligands and methods of use thereof
4-(1-cyclohex-3-enyl)-6-methoxy-8-nitro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline	EC50	6.9 nM
(2R,6S,7R)-12-hydroxy-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-4-one	KI	6.92 nM
4-ethenyl-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinolin-1-one	KI	7 nM	US-9623021: Nuclear receptor binding agents
2-(4-hydroxyphenyl)-3-{4-[2-(piperidin-1-yl)ethoxy]phenoxy}-1-benzothiophen-6-ol	IC50	9.6 nM
racemic mixture	KI	10.2 nM
5,7-dihydroxy-3-(4-hydroxyphenyl)-3,4-dihydroquinazoline-4-thione	EC50	13 nM
(5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol	IC50	13 nM
CHEMBL4213948	KI	13 nM
5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromene-4-thione	EC50	14 nM
2-(4-hydroxy-2-methylphenyl)-1-benzothiophen-6-ol	EC50	15 nM
3-fluoro-N-(4-fluorophenyl)-4-hydroxy-N-(4-hydroxyphenyl)benzamide	KI	15.2 nM	US-8546451: Estrogen receptor ligands and methods of use thereof
2-phenyl-3-{4-[2-(piperidin-1-yl)ethoxy]phenoxy}-1-benzothiophen-6-ol	IC50	16.3 nM

ChEMBL bioactivities

3747 potent at pChembl≥5 of 4025 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	EC50	0.01	nM	ESTRADIOL
11.00	IC50	0.01	nM	ESTRADIOL
10.85	Ki	0.014	nM	CHEMBL2137046
10.82	Ki	0.015	nM	ACOLBIFENE
10.82	Ki	0.015	nM	ESTRADIOL
10.80	Ki	0.016	nM	CHEMBL308234
10.70	EC50	0.02	nM	ESTRADIOL
10.70	EC50	0.02	nM	DIETHYLSTILBESTROL
10.66	EC50	0.022	nM	ESTRADIOL
10.64	Ki	0.023	nM	CHEMBL308234
10.60	Ki	0.025	nM	CHEMBL1627464
10.55	Ki	0.028	nM	CHEMBL291808
10.54	EC50	0.029	nM	CHEMBL4782490
10.52	EC50	0.0301	nM	ESTRADIOL
10.44	EC50	0.036	nM	ESTRADIOL
10.41	EC50	0.039	nM	ESTRADIOL
10.40	EC50	0.03981	nM	ESTRADIOL
10.40	EC50	0.04	nM	ESTRADIOL
10.38	Ki	0.042	nM	ACOLBIFENE
10.34	IC50	0.046	nM	ESTRADIOL
10.33	Ki	0.047	nM	ACOLBIFENE
10.32	Ki	0.048	nM	CHEMBL128227
10.30	IC50	0.05	nM	CHEMBL537254
10.30	EC50	0.05	nM	CHEMBL4753115
10.22	Ki	0.06	nM	CHEMBL315474
10.21	EC50	0.06166	nM	ESTRADIOL
10.16	Ki	0.069	nM	ACOLBIFENE
10.15	IC50	0.07	nM	CHEMBL181248
10.15	EC50	0.07	nM	ESTRADIOL
10.15	EC50	0.07	nM	CHEMBL1222144
10.12	Ki	0.076	nM	ACOLBIFENE
10.07	EC50	0.085	nM	ESTRADIOL
10.05	Ki	0.09	nM	ACOLBIFENE
10.01	EC50	0.098	nM	ESTRADIOL
10.00	IC50	0.1	nM	LASOFOXIFENE
10.00	EC50	0.1	nM	ESTRADIOL
10.00	EC50	0.1	nM	CHEMBL4740602
10.00	EC50	0.0996	nM	ESTRADIOL
9.95	Ki	0.113	nM	ESTRADIOL
9.92	Ki	0.12	nM	ESTRADIOL
9.90	Ki	0.126	nM	DIETHYLSTILBESTROL
9.90	EC50	0.1259	nM	ESTRIOL
9.89	Ki	0.128	nM	DIETHYLSTILBESTROL
9.89	EC50	0.13	nM	ESTRADIOL
9.86	Ki	0.138	nM	ESTRADIOL
9.85	IC50	0.14	nM	CHEMBL308234
9.85	IC50	0.14	nM	ACOLBIFENE
9.85	EC50	0.14	nM	CHEMBL134938
9.82	IC50	0.15	nM	CHEMBL183162
9.82	EC50	0.151	nM	ESTRADIOL

PubChem BioAssay actives

2203 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(NE)-N-[[2-(ethylamino)-3,4-diphenylphenyl]methylidene]hydroxylamine	70037: Relative binding affinity for human estrogen receptor beta compared to [3H]-estradiol	ki	<0.0001	uM
(2S)-3-(4-hydroxyphenyl)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2H-chromen-7-ol	210119: Apparent binding affinity against estradiol-stimulated T-47D cell proliferation	ki	<0.0001	uM
(8S,9R,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,11,12,14,15,16,17-octahydro-6H-cyclopenta[a]phenanthrene-9-carbonitrile	1724581: Agonist activity at full length human ERbeta receptor assessed as transcriptional activity incubated for 22 to 24 hrs by cell based luciferase reporter gene assay	ec50	<0.0001	uM
(2R,3R,4S)-5-fluoro-3-(4-hydroxyphenyl)-4-methyl-2-[4-[(2S)-2-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-3,4-dihydro-2H-chromen-6-ol	248124: Inhibition of estrogen dependent human MCF-7 cell proliferation	ic50	0.0001	uM
1-[1-(4-hydroxyphenyl)propyl]-2,3-dihydro-1H-inden-5-ol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0001	uM
1-[(2-chloro-4-hydroxyphenyl)methyl]-5-hydroxy-2,3-dihydroindene-1-carbonitrile	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0001	uM
1-[(2-fluoro-4-hydroxyphenyl)methyl]-5-hydroxy-2,3-dihydroindene-1-carbonitrile	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0001	uM
5-[(4-hydroxyphenyl)methyl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-ol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0001	uM
(5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol	247489: Inhibition of MCF-7 cell proliferation	ic50	0.0001	uM
4-[(E)-4-(4-hydroxyphenyl)-10-[methyl-[3-(4,4,5,5,5-pentafluoropentylsulfanyl)propyl]amino]dec-3-en-3-yl]phenol	248483: Inhibition of ER-MDA-MB 231 breast cancer cell proliferation over 200 hr	ic50	0.0002	uM
(3aS,4R,9bR)-4-(4-hydroxyphenyl)-1,2,3,3a,4,9b-hexahydrocyclopenta[c]chromen-8-ol	1797927: Estrogen Receptor Binding Assay from Article 10.1021/jm060491j: “Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia.”	ki	0.0002	uM
Fulvestrant	248483: Inhibition of ER-MDA-MB 231 breast cancer cell proliferation over 200 hr	ic50	0.0002	uM
2-(4-hydroxyphenyl)-1-[4-(2-piperidin-1-ylethoxy)phenyl]-3H-inden-5-ol	254433: Antagonistic activity against estrogen receptor beta in presence of 0.1 nM estradiol	ki	0.0002	uM
3-chloro-2-[(E)-hydroxyiminomethyl]-4-(4-hydroxyphenyl)phenol	601686: Agonist activity at human full-length ERbeta receptor expressed in human HEC1 cells co-expressing (ERE)2-pS2-luc gene assessed as transcriptional activation after 24 hrs by luciferase reporter gene assay	ec50	0.0002	uM
(9aS)-9a-ethyl-1-fluoro-6-(trifluoromethyl)-2,8,9,10-tetrahydroindeno[2,1-e]indazol-7-one	269190: Agonist activity at human ERbeta transfected in HEK293 cells assessed as transactivation of alkaline phosphatase reporter gene	ec50	0.0002	uM
5-[(4-hydroxyphenyl)methyl]-5,6,7,8-tetrahydronaphthalen-2-ol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0002	uM
4-[2-(4-hydroxyphenyl)butyl]phenol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0002	uM
5-[4-(2-piperidin-1-ylethoxy)phenyl]-6H-benzo[c]phenanthridine-2,8-diol	70973: Displacement of [3H]17-beta-estradiol from MCF-7 cell lysate	ki	0.0003	uM
1-ethyl-2-(4-hydroxyphenyl)-3H-inden-5-ol	254647: Transcriptional activation of estrogen receptor beta in U2OS cell using estrogen-regulated luciferase reporter gene plasmid upon incubation for 20-30 mins at RT	ec50	0.0003	uM
(3S,4R)-3-phenyl-4-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-3,4-dihydro-1H-isothiochromen-7-ol	247489: Inhibition of MCF-7 cell proliferation	ic50	0.0003	uM
1,3-diethyl-2-(4-hydroxyphenyl)-3H-inden-5-ol	254647: Transcriptional activation of estrogen receptor beta in U2OS cell using estrogen-regulated luciferase reporter gene plasmid upon incubation for 20-30 mins at RT	ec50	0.0003	uM
6-(4-fluorophenyl)-5-[4-(2-piperidin-1-ylethoxy)phenoxy]naphthalen-2-ol;hydrochloride	255900: Half maximal inhibitory concentration against estrogen-induced proliferation of MCF-7 breast cells by 10 pM E2	ic50	0.0003	uM
6-(4-fluorophenyl)-5-[4-(2-piperidin-1-ylethoxy)phenoxy]naphthalen-2-ol	1797926: Estrogen Receptor Binding Assay and Ishikawa Assay from Article 10.1021/jm050723z: “A selective estrogen receptor modulator designed for the treatment of uterine leiomyoma with unique tissue specificity for uterus and ovaries in rats.”	ki	0.0003	uM
(NE)-N-[(3,4-diphenylphenyl)methylidene]hydroxylamine	70037: Relative binding affinity for human estrogen receptor beta compared to [3H]-estradiol	ki	0.0003	uM
(3aS,4R,9bR)-4-(4-hydroxyphenyl)-6-methyl-1,2,3,3a,4,9b-hexahydrocyclopenta[c]chromen-8-ol	1797930: Estrogen Receptor Binding Assay. from Article 10.1016/j.bmcl.2007.07.009: “Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: functionalization of the benzopyran A-ring.”	ki	0.0003	uM
(2S,3R)-3-(4-hydroxyphenyl)-2-[4-[2-[(2R)-2-methylpyrrolidin-1-yl]ethoxy]phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol	248196: In vitro inhibition of estradiol-stimulated MCF-7 breast cancer cell proliferation	ic50	0.0004	uM
3-(4-hydroxy-2-methylphenyl)-2-(4-hydroxyphenyl)propanenitrile	70021: Transcriptional potency (EC50) at Human estrogen receptor Beta	ec50	0.0004	uM
(3aS,4R,9bR)-2,2-difluoro-4-(4-hydroxyphenyl)-3,3a,4,9b-tetrahydro-1H-cyclopenta[c]chromen-8-ol	1797929: Estrogen Receptor Binding Assay. from Article 10.1016/j.bmcl.2007.06.052: “Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification.”	ki	0.0004	uM
(2R,3aS,4R,9bR)-4-(4-hydroxyphenyl)-2-(trifluoromethyl)-1,2,3,3a,4,9b-hexahydrocyclopenta[c]chromen-8-ol	1797929: Estrogen Receptor Binding Assay. from Article 10.1016/j.bmcl.2007.06.052: “Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification.”	ki	0.0004	uM
(2R,3R,4S)-3-(4-hydroxyphenyl)-4-methyl-2-[4-[(2S)-2-[(3R)-3-methylpyrrolidin-1-yl]propoxy]phenyl]-3,4-dihydro-2H-chromen-6-ol	248124: Inhibition of estrogen dependent human MCF-7 cell proliferation	ic50	0.0004	uM
6-(3-hydroxyphenyl)-5-[4-(2-piperidin-1-ylethoxy)phenoxy]naphthalen-2-ol	290755: Displacement of [3H]estradiol from human recombinant ERbeta	ki	0.0004	uM
(9aR)-9a-ethyl-6-(trifluoromethyl)-8,9-dihydro-3H-indeno[2,3-e]indazole-7,10-dione	269190: Agonist activity at human ERbeta transfected in HEK293 cells assessed as transactivation of alkaline phosphatase reporter gene	ec50	0.0004	uM
1-ethyl-1-[(4-hydroxyphenyl)methyl]-2,3-dihydroinden-5-ol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0004	uM
1-[(4-hydroxyphenyl)methyl]-1-methyl-2,3-dihydroinden-5-ol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0004	uM
(2S,3R)-3-(4-hydroxyphenyl)-2-[4-[2-[(2S)-2-methylpyrrolidin-1-yl]ethoxy]phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol	248196: In vitro inhibition of estradiol-stimulated MCF-7 breast cancer cell proliferation	ic50	0.0005	uM
(2S,3R)-2-[4-[2-[(3R,4S)-3,4-dimethylpyrrolidin-1-yl]ethoxy]phenyl]-3-(4-hydroxyphenyl)-2,3-dihydro-1,4-benzoxathiin-6-ol	248196: In vitro inhibition of estradiol-stimulated MCF-7 breast cancer cell proliferation	ic50	0.0005	uM
4-bromo-2-(4-hydroxyphenyl)-7-methoxy-1-benzofuran-5-ol	241825: Binding affinity for human Estrogen receptor beta	ic50	0.0005	uM
4-[5-(4-hydroxyphenyl)-3-methyl-4-[4-(2-piperidin-1-ylethoxy)phenyl]furan-2-yl]phenol	70659: Displacement of [3H]estradiol from Estrogen receptor beta	ki	0.0005	uM
4-[5-hydroxy-2-(4-hydroxyphenyl)-3H-inden-1-yl]benzamide	254433: Antagonistic activity against estrogen receptor beta in presence of 0.1 nM estradiol	ki	0.0005	uM
(2R,3R,4S)-5-fluoro-3-(4-hydroxyphenyl)-4-methyl-2-[4-[(2S)-2-pyrrolidin-1-ylpropoxy]phenyl]-3,4-dihydro-2H-chromen-6-ol	248124: Inhibition of estrogen dependent human MCF-7 cell proliferation	ic50	0.0005	uM
3-(2-fluoro-4-hydroxyphenyl)-7-hydroxynaphthalene-1-carbonitrile	242135: Inhibition of [3H]17-beta-estradiol binding to human estrogen receptor beta expressed in Escherichia coli	ic50	0.0005	uM
(5R)-7,9-difluoro-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5H-naphtho[1,2-c]chromen-2-ol;hydrochloride	259855: Displacement of [3H]17beta-estradiol from ERbeta	ki	0.0005	uM
1-(4-chlorophenyl)-2-(4-hydroxyphenyl)-3H-inden-5-ol	254433: Antagonistic activity against estrogen receptor beta in presence of 0.1 nM estradiol	ki	0.0005	uM
2-[(E)-hydroxyiminomethyl]-3,4-bis(4-hydroxyphenyl)phenol	601686: Agonist activity at human full-length ERbeta receptor expressed in human HEC1 cells co-expressing (ERE)2-pS2-luc gene assessed as transcriptional activation after 24 hrs by luciferase reporter gene assay	ec50	0.0005	uM
[(2S,3R)-6-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone	103918: Inhibition of 17-beta-estradiol (10e-11 M) mediated MCF-7 cell proliferation	ic50	0.0005	uM
5-hydroxy-1-[(4-hydroxy-2-methylphenyl)methyl]-2,3-dihydroindene-1-carbonitrile	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0005	uM
1-[(4-hydroxyphenyl)methyl]-1-propyl-2,3-dihydroinden-5-ol	1713770: Agonist activity at human ERbeta receptor expressed in HEK293T cells transfected with pGL4.27-(ERE)3-Luc assessed as transcriptional activation measured after 16 hrs by Dual-Glo luciferase assay	ec50	0.0005	uM
(3aS,4R,9bR)-2,2-difluoro-4-(4-hydroxyphenyl)-6-(methoxymethyl)-3,3a,4,9b-tetrahydro-1H-cyclopenta[c]chromen-8-ol	1797931: Estrogen Receptor Binding Assay. from Article 10.1016/j.bmcl.2007.08.009: “Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 5: Combined A- and C-ring structure-activity relationship studies.”	ki	0.0005	uM
Tamoxifen	669589: Displacement of [3H]estradiol from ERbeta after 4 hrs by scintillation counting	ki	0.0005	uM
(6S,6aR,10aS)-6-(4-hydroxyphenyl)-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-2-ol	299254: Binding affinity to human ERbeta	ki	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases response to substance, decreases reaction, affects binding (+16 more)	149
bisphenol A	increases expression, affects reaction, decreases expression, decreases reaction, affects expression (+6 more)	77
Genistein	affects binding, affects cotreatment, increases expression, affects expression, decreases expression (+6 more)	43
Fulvestrant	decreases expression, increases reaction, increases response to substance, decreases reaction, increases expression (+8 more)	33
Tamoxifen	affects binding, increases reaction, affects reaction, decreases activity, decreases expression (+7 more)	27
daidzein	affects binding, affects cotreatment, decreases expression, decreases reaction, increases reaction (+6 more)	22
Diethylstilbestrol	increases expression, decreases reaction, increases reaction, affects binding, increases activity (+1 more)	18
Quercetin	increases reaction, decreases expression, increases response to substance, increases cleavage, affects binding (+4 more)	14
Raloxifene Hydrochloride	decreases expression, increases expression, increases activity, increases response to substance, affects binding (+6 more)	12
afimoxifene	affects expression, decreases activity, increases reaction, increases expression, increases response to substance (+4 more)	11
Resveratrol	increases activity, affects binding, increases expression, decreases activity, decreases expression (+2 more)	10
Coumestrol	decreases reaction, affects reaction, increases expression, affects binding, increases activity (+3 more)	10
2,3-bis(4-hydroxyphenyl)-propionitrile	increases activity, decreases activity, decreases reaction, increases localization, affects reaction (+3 more)	9
bisphenol S	increases phosphorylation, decreases reaction, affects binding, increases activity, decreases expression (+2 more)	9
bisphenol AF	increases activity, decreases reaction, increases expression, affects binding, affects reaction	9
naringenin	increases expression, affects binding, increases activity, affects cotreatment, decreases reaction	8
kaempferol	affects binding, decreases reaction, affects reaction, increases activity	8
Ethinyl Estradiol	affects binding, increases activity, decreases expression, decreases reaction, increases reaction (+1 more)	8
Methoxychlor	increases reaction, affects binding, decreases activity, decreases reaction, affects activity (+1 more)	8
4-tert-octylphenol	decreases reaction, increases reaction, increases expression, affects binding, increases activity	7
4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol	affects binding, decreases activity, decreases reaction, increases expression, decreases phosphorylation (+1 more)	7
Zearalenone	increases activity, increases reaction, decreases activity, affects localization, affects binding	7
Equol	decreases reaction, affects activity, affects reaction, affects binding, increases activity (+1 more)	7
biochanin A	increases activity, decreases reaction, affects binding	6
nonylphenol	decreases reaction, affects binding, increases activity	6
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane	affects binding, decreases activity, increases activity, decreases reaction, increases expression	6
4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene	affects binding, affects reaction, increases expression	6
Estriol	affects binding, increases activity, decreases reaction	6
Apigenin	affects binding, increases activity, decreases reaction	6
formononetin	affects binding, increases activity	5

ChEMBL screening assays

1113 unique, capped per target: 837 binding, 265 functional, 11 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4188356	Binding	Estrogenic activity at ERalpha/ERbeta (unknown origin) expressed in human HepG2 cells co-expressing ERE-dependent promoter assessed as increase in ER-mediated transcriptional activation at 1 uM incubated for 24 hrs by luciferase reporter ge	Estrogenic activity of constituents from the rhizomes of Rheum undulatum Linné. — Bioorg Med Chem Lett
CHEMBL4219456	ADMET	Estrogenic activity at estrogen receptor alpha/beta in human Ishikawa cells at 1 uM after 72 hrs by alkaline phosphatase assay relative to estradiol	Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity. — J Med Chem
CHEMBL654137	Functional	IC50 determined against human estrogen receptor in CV-1 cells	5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal human progesterone receptor agonists. — J Med Chem

Cellosaurus cell lines

13 cell lines: 8 cancer cell line, 3 embryonic stem cell, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1K7	SEES3-1V human ESR2, clone1	Embryonic stem cell	Male
CVCL_A1K8	SEES3-1V human ESR2, clone2	Embryonic stem cell	Male
CVCL_A1K9	SEES3-1V human ESR2, clone3	Embryonic stem cell	Male
CVCL_DD13	BG1LucERbc9	Cancer cell line	Female
CVCL_E1WH	HAP1 ESR2 (-) 2	Cancer cell line	Male
CVCL_E1WI	HAP1 ESR2 (-) 3	Cancer cell line	Male
CVCL_E1WJ	HAP1 ESR2 (-) 4	Cancer cell line	Male
CVCL_IN18	MDA-MB-231 ERbeta	Cancer cell line	Female
CVCL_IN19	MDA-MB-231 ERbetaDBD	Cancer cell line	Female
CVCL_RR09	MCF10A ESR2 (-/-)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT07383246	PHASE3	RECRUITING	CTR-FAPI-guided Precision Surgery for Newly Diagnosed MTC
NCT01736878	PHASE2	WITHDRAWN	Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma
NCT04787328	PHASE2	UNKNOWN	A Study of HA121-28 Tablets in Patients With Medullary Thyroid Carcinoma (MTC)
NCT06121271	PHASE2	NOT_YET_RECRUITING	Trial of Lu-177 DOTATATE (Lutathera®) in Unlicensed Indications
NCT03246659	PHASE1	COMPLETED	Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC
NCT06520319	PHASE1	RECRUITING	Head-to-head Study of 68Ga-MGS5 Versus 68Ga-DOTATATE PET/CT in Patients With Medullary Thyroid Carcinoma
NCT02586350	PHASE2/PHASE3	COMPLETED	Study of Anlotinib in Patients With Medullary Thyroid Carcinoma(ALTER01031)
NCT00514046	PHASE1/PHASE2	COMPLETED	Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer
NCT00923247	PHASE1/PHASE2	TERMINATED	A Targeted Phase I/II Trial of ZD6474 (Vandetanib; ZACTIMA) Plus the Proteasome Inhibitor, Bortezomib (Velcade ), in Adults With Solid Tumors With a Focus on Hereditary or Sporadic, Locally Advanced or Metastatic Medullary Thyroid Cancer (MTC)
NCT01730638	PHASE1/PHASE2	COMPLETED	ImmunoTEP for Patients With Medullary Thyroid Carcinoma.
NCT00880503	Not specified	COMPLETED	Collection of Tissue Samples for Study of Multidrug Resistance
NCT01424878	Not specified	COMPLETED	Study of Molecular Pathways in Medullary Thyroid Carcinoma and Correlation of Molecular Data With Clinical Behavior of the MTC in Individuals Patients
NCT01511393	Not specified	ENROLLING_BY_INVITATION	An Active Surveillance Program for Cases of Medullary Thyroid Carcinoma (MTC)
NCT03636945	Not specified	UNKNOWN	Evaluation of 18F-FDOPA PET-CT in the Preoperative Initial Assessment of Medullary Thyroid Carcinoma
NCT04970134	Not specified	ACTIVE_NOT_RECRUITING	Spanish Study for Molecular Characterization of Thyroid Carcinoma
NCT05534594	Not specified	COMPLETED	Evaluation of the 18F-PSMA Positron Emission Tomography (PET)/CT in Patients With Medullary Thyroid Cancer
NCT06067594	Not specified	COMPLETED	Calcitonin in Needle Wash Using Electrochemiluminescence Method For Diagnosis Of Medullary Thyroid Carcinoma.
NCT06852144	Not specified	ENROLLING_BY_INVITATION	PET-TC in Thyroid Evaluation
NCT07138716	Not specified	RECRUITING	Research on the Application of 68Ga-DOTA-CCK-FS PET/CT in MTC