STAT6

Summary

STAT6 (signal transducer and activator of transcription 6, HGNC:11368) is a protein-coding gene on chromosome 12q13.3, encoding Signal transducer and activator of transcription 6 (P42226). Carries out a dual function: signal transduction and activation of transcription.

The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6778 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyper-IgE syndrome 6, autosomal dominant, with recurrent infections (Strong, ClinGen)
• GWAS associations: 59
• Clinical variants (ClinVar): 141 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Transcription factor: yes — 138 downstream targets (CollecTRI)
• MANE Select transcript: NM_003153

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11368
Approved symbol	STAT6
Name	signal transducer and activator of transcription 6
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	D12S1644, IL-4-STAT
Ensembl gene	ENSG00000166888
Ensembl biotype	protein_coding
OMIM	601512
Entrez	6778

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 35 protein_coding, 6 retained_intron, 6 nonsense_mediated_decay

ENST00000300134, ENST00000454075, ENST00000537215, ENST00000538913, ENST00000543873, ENST00000553275, ENST00000553397, ENST00000553499, ENST00000553533, ENST00000554202, ENST00000554764, ENST00000555104, ENST00000555222, ENST00000555318, ENST00000555375, ENST00000555641, ENST00000555849, ENST00000556155, ENST00000556259, ENST00000557563, ENST00000557635, ENST00000557781, ENST00000640254, ENST00000651176, ENST00000714370, ENST00000714371, ENST00000714372, ENST00000714373, ENST00000714374, ENST00000861685, ENST00000861686, ENST00000861687, ENST00000861688, ENST00000861689, ENST00000861690, ENST00000861691, ENST00000920257, ENST00000920258, ENST00000920259, ENST00000953180, ENST00000953181, ENST00000953182, ENST00000953183, ENST00000953184, ENST00000953185, ENST00000953186, ENST00000953187

RefSeq mRNA: 5 — MANE Select: NM_003153 NM_001178078, NM_001178079, NM_001178080, NM_001178081, NM_003153

CCDS: CCDS53804, CCDS8931

Canonical transcript exons

ENST00000300134 — 22 exons

Exon	Start	End
ENSE00001107465	57095408	57096761
ENSE00001353600	57111129	57111362
ENSE00003275456	57108163	57108299
ENSE00003458544	57096850	57096978
ENSE00003484230	57107231	57107314
ENSE00003491794	57099767	57099903
ENSE00003500520	57107605	57107743
ENSE00003520637	57098505	57098597
ENSE00003547481	57098792	57098902
ENSE00003553085	57099294	57099440
ENSE00003557323	57099015	57099078
ENSE00003576863	57106191	57106339
ENSE00003598889	57099996	57100090
ENSE00003603066	57104726	57104813
ENSE00003606856	57104464	57104586
ENSE00003622644	57097068	57097133
ENSE00003635281	57106528	57106580
ENSE00003659238	57102829	57102921
ENSE00003661799	57102290	57102496
ENSE00003663096	57105468	57105599
ENSE00003686557	57105151	57105339
ENSE00003790783	57106693	57106831

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8048 / max 517.7107, expressed in 1788 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131635	30.0051	1776
131634	3.3396	1256
131637	0.5251	295
131632	0.3365	186
131636	0.2783	106
131639	0.2045	102
131633	0.1158	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.21	gold quality
right ovary	UBERON:0002118	98.79	gold quality
left ovary	UBERON:0002119	98.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.77	gold quality
endocervix	UBERON:0000458	98.68	gold quality
spleen	UBERON:0002106	98.62	gold quality
mucosa of stomach	UBERON:0001199	98.61	gold quality
lower esophagus mucosa	UBERON:0035834	98.58	gold quality
right adrenal gland cortex	UBERON:0035827	98.57	gold quality
right uterine tube	UBERON:0001302	98.50	gold quality
left uterine tube	UBERON:0001303	98.49	gold quality
body of uterus	UBERON:0009853	98.49	gold quality
transverse colon	UBERON:0001157	98.48	gold quality
right adrenal gland	UBERON:0001233	98.48	gold quality
monocyte	CL:0000576	98.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.47	gold quality
descending thoracic aorta	UBERON:0002345	98.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.46	gold quality
leukocyte	CL:0000738	98.45	gold quality
mononuclear cell	CL:0000842	98.44	gold quality
metanephros cortex	UBERON:0010533	98.44	gold quality
ileal mucosa	UBERON:0000331	98.41	gold quality
right coronary artery	UBERON:0001625	98.41	gold quality
lower esophagus	UBERON:0013473	98.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.41	gold quality
skin of abdomen	UBERON:0001416	98.40	gold quality
ectocervix	UBERON:0012249	98.40	gold quality
upper lobe of left lung	UBERON:0008952	98.37	gold quality
right lung	UBERON:0002167	98.36	gold quality
body of stomach	UBERON:0001161	98.34	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.65
E-MTAB-7606	no	518.39
E-MTAB-6379	no	204.47

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

138 targets.

Target	Regulation
ADRA2B	Unknown
ALOX12	Unknown
ALOX15	Activation
ANXA2
ARG1
ATP11C
BATF	Activation
BCL2L1	Unknown
BCL6
CCL1	Activation
CCL11	Activation
CCL13	Activation
CCL17	Activation
CCL2	Repression
CCL23
CCL26	Activation
CCL7	Repression
CCL8	Repression
CCR4	Unknown
CCR8	Unknown
CD4	Unknown
CD40	Unknown
CD86	Unknown
CDKN1A	Unknown
CDKN1B
CDKN2A
CEL
CHI3L1	Activation
CISH	Unknown
CNR1	Activation

Upstream regulators (CollecTRI, top): BCL6, CEBPB, CUX1, HAND2, HDAC9, MYC, NFKB, PRDM1, SFPQ, SPI1, STAT1, STAT6, TBX21, TP63

miRNA regulators (miRDB)

52 targeting STAT6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662

Literature-anchored findings (GeneRIF, showing 40)

• IL-4-dependent Stat6 activation is inhibited by an intracellularly delivered peptide derived from the Stat6-binding region of IL-4Ralpha. (PMID:11532018)
• role in mediating responses of bronchial epithelium to cytokines in asthmatics (PMID:11692112)
• Oligonucleotide fishing for STAT6: cross-talk between IL-4 and chemokines. (PMID:11872954)
• STAT6 polymorphism is associated with increase in eosinophil cell count contributing to the pathogenesis of Asthma (PMID:11912176)
• 3’UTR polymorphism is associated with susceptibility and severity in nut allergic patients (PMID:12058257)
• STAT6 is required for IL-4-mediated growth inhibition and induction of apoptosis in human breast cancer cells. (PMID:12082548)
• STAT6 has a protein binding motif that controls the interaction with NcoA-1 in transcriptional activation (PMID:12138096)
• These results show that p38 MAPK provides a costimulatory signal for IL-4-induced gene responses by directly stimulating the transcriptional activation of STAT6. (PMID:12161424)
• These findings identify p100 as a novel coactivator for STAT6 and suggest that p100 functions as a bridging factor between STAT6 and the basal transcription machinery. (PMID:12234934)
• Protein phosphatase 2A (PP2A) regulates interleukin-4-mediated signaling by this protein. (PMID:12426308)
• regulation of dephosphorylation by of mitogen-activated protein kinase and myosin light chain kinase (PMID:12459556)
• IL-4-induced Stat6 signaling is a polygenic quantitative trait regulated by a collection of several contributing genetic loci. (PMID:12651067)
• when osteoclastogenesis was induced independently of RANKL by using TNF-alpha, IL-4 inhibited osteoclast differentiation through a STAT6-dependent mechanism (PMID:12689929)
• Characterization of the IL-4-responsive enhanceosome of the human polymeric Ig receptor gene demonstrates cooperation of STAT6, HNF1 and additional DNA-binding factors in mediating IL-4 responsiveness in HT-29 cells. (PMID:12794133)
• These results suggest that MIP-T3 is a novel inhibitor of IL-13 signaling and may be a useful molecule in ameliorating various conditions in which IL-13 plays a central role. (PMID:12935900)
• the Stat6 TAD contributes to promoter specificity by the differential recruitment of and requirement for a p160-class coactivator (PMID:14519766)
• STAT6 is required for IL-4-IL-13-dependent SOCS-1 expression in A549 human lung adenocarcinoma cells; three identified STAT6-binding motifs in the SOCS-1 promoter cooperate to induce maximal transcription. (PMID:14634100)
• the Stat6 signaling pathway may play a role in maintaining the Th1/Th2 cytokine balance by directly and indirectly down-regulating the production of proinflammatory cytokines (PMID:14719123)
• Results demonstrate that induction of adenine nucleotide translocase 3 by interleukin-4 and interferon-gamma proceeds via pathways involving STAT6 and STAT1, respectively. (PMID:14746803)
• STAT6 activation mediates a transcriptional enhancement of trefoil factor-3 (TFF3) by induction of de novo synthesized protein in mucus-producing HT-29 CL.16E intestinal goblet cells. (PMID:15004182)
• Constitutive STAT6 phosphorylation and DNA-binding activity were detected in primary mediastinal large B-cell lymphoma cell lines but not diffuse large B-cell lymphoma cell lines (PMID:15044251)
• IL-4 and IL-13 promote Stat6 serine phosphorylation in PHA-activated human T-cells. (PMID:15069079)
• As no exonic variants of STAT6 are known as yet, repeat polymorphisms in the regulatory regions and their haplotypes could be important in deciphering the genetic role of STAT6 in asthma and atopy. (PMID:15105161)
• FN-gamma regulates IL-4- and STAT6-dependent signaling and gene expression in airway epithelial cells by multiple mechanisms (PMID:15297269)
• genetic variants within STAT6 contribute significantly to IgE regulation and manifestation of atopic diseases (PMID:15342695)
• Role for Stat6 in apoptosis regulation. Stat6(null phenotype) cell lines exhibit variably increased levels of Th1 cytokines. May be source for investigations into Inflammatory bowel disease pathophysiology. (PMID:15522309)
• IL-4 and IL-13 mediate the hypercontractility of intestinal muscle via a STAT6 pathway at the level of the smooth muscle cell. The STAT6 pathway may contribute to the hypercontractility of intestinal muscle in Crohn’s disease. (PMID:15528258)
• p100 has an important role in the assembly of STAT6 transcriptosome, and that p100 stimulates IL-4-dependent transcription by mediating interaction between STAT6 and CBP and recruiting chromatin modifying activities to STAT6-responsive promoters (PMID:15695802)
• PI3-K promotes the expression of TFF3 and MUC2 and that the PI3-K pathway may play a pivotal role in intestinal goblet cell differentiation. (PMID:15733066)
• Alterations in the STAT6 pathway may play a crucial role in the pathogenesis of distinct subgroups of patients with Crohn’s disease. (PMID:15888279)
• IL-4 regulates TNFalpha-induced IL-8 expression at a transcriptional level and this mechanism involves STAT6 and NF-kappaB transcription factors (PMID:16004996)
• results demonstrate that epithelial eotaxin-3 is up-regulated in the context of a T helper 2 mediated inflammatory bowel disease via the signal transducer and activator of transcription 6 (PMID:16084752)
• Findings suggest that Stat6 signaling pathway plays a role in the regulation of cell proliferation and apoptosis in colon cancer cells, which promises further investigation for targeted cancer therapy. (PMID:16387423)
• STAT6 binding to STAT6 promotor gene was regulated by H4 receptor-induced signal transduction and/or cross talk particularly in atopic human lymphocytes ex vivo (PMID:16547812)
• IL-4 has differential effects in coronary artery smooth muscle cells: short-term exposure enhances OPG production through a STAT6-dependent mechanism, but long-term exposure causes Cbfa1-dependent osteogenic transformation and decreased production of OPG (PMID:16601843)
• Essential for IL-4-induced human T-cell expression of CCL17/thymus- and activation-regulated chemokine(TARC). (PMID:16810739)
• Activation of STAT6 appears to be a key factor in P-selectin expression induced by substance P and IL-4 because treatment with STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. (PMID:16877367)
• Stat6 exerts a stimulatory effect on early growth response (Egr)-1 gene and platelet-derived growth factor (PDGF) ligand mRNA transcription. (PMID:16951379)
• The STAT6 G2964A polymorphism is not involved in the genetic susceptibility to ulcerative colitis in Chinese patients. (PMID:17074026)
• specific increases in T-cell protein tyrosine phosphatase expression in activated-B-cell-like diffuse large B-cell lymphomas may contribute to the different biological characteristics of these tumors (PMID:17210636)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stat6	ENSDARG00000015902
mus_musculus	Stat6	ENSMUSG00000002147
rattus_norvegicus	Stat6	ENSRNOG00000025023
drosophila_melanogaster	Stat92E	FBGN0016917

Paralogs (6): STAT1 (ENSG00000115415), STAT5A (ENSG00000126561), STAT4 (ENSG00000138378), STAT3 (ENSG00000168610), STAT2 (ENSG00000170581), STAT5B (ENSG00000173757)

Protein

Protein identifiers

Signal transducer and activator of transcription 6 — P42226 (reviewed: P42226)

Alternative names: IL-4 Stat

All UniProt accessions (14): P42226, A0A1W2PNW1, A0A494C0T4, A0AAQ5BHX1, A0AAQ5BI40, G3V2L2, G3V2M3, G3V370, G3V568, G3V5I8, G3V5K5, H0YIY2, H0YJH6, Q5FBW6

UniProt curated annotations — full annotation on UniProt →

Function. Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling.

Subunit / interactions. Forms a homodimer or a heterodimer with a related family member. Interacts with NCOA1 via its C-terminal LXXLL motif.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Tyrosine phosphorylated on Tyr-641 following stimulation by IL4/interleukin-4. Tyrosine phosphorylated following stimulation by IL3/interleukin-3. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates the IL4/interleukin-4 mediated signaling. Mono-ADP-ribosylated by PARP14.

Disease relevance. Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections (HIES6) [MIM:620532] An immunologic disorder characterized by severe allergic disease with onset in infancy. Common features are treatment-resistant atopic dermatitis, food allergies, asthma, eosinophilic gastrointestinal disease, and severe episodes of anaphylaxis. Half of the patients present with recurrent skin, respiratory, and viral infections. Clinical laboratory testing is notable for eosinophilia and markedly elevated serum IgE levels. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the transcription factor STAT family.

Isoforms (3)

UniProt ID	Names	Canonical?
P42226-1	1	yes
P42226-2	2
P42226-3	3

RefSeq proteins (5): NP_001171549, NP_001171550, NP_001171551, NP_001171552, NP_003144* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001217	STAT	Family
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR012345	STAT_TF_DNA-bd_N	Homologous_superfamily
IPR013799	STAT_TF_prot_interaction	Domain
IPR013800	STAT_TF_alpha	Domain
IPR013801	STAT_TF_DNA-bd	Domain
IPR015988	STAT_TF_CC	Homologous_superfamily
IPR028187	STAT6_C	Domain
IPR035857	STAT6_SH2	Domain
IPR036535	STAT_N_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR048988	STAT_linker	Domain

Pfam: PF00017, PF01017, PF02864, PF02865, PF14596, PF21354

UniProt features (75 total): strand 22, helix 19, sequence variant 12, turn 6, mutagenesis site 3, sequence conflict 3, splice variant 3, modified residue 2, initiator methionine 1, chain 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1OJ5	X-RAY DIFFRACTION	2.21
5NWX	X-RAY DIFFRACTION	2.51
4Y5U	X-RAY DIFFRACTION	2.71
4Y5W	X-RAY DIFFRACTION	3.1
5D39	X-RAY DIFFRACTION	3.2
9BIG	X-RAY DIFFRACTION	3.3
5NWM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42226-F1	77.44	0.55

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): 2, 641

Mutagenesis-validated functional residues (3):

Position	Phenotype
641	abolishes phosphorylation. loss of dna-binding transcription factor activity.
802	abolishes the interaction with ncoa1; when associated with a-805.
805	abolishes the interaction with ncoa1; when associated with a-802.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-186763	Downstream signal transduction
R-HSA-3249367	STAT6-mediated induction of chemokines
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-1834941	STING mediated induction of host immune responses
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA
R-HSA-186797	Signaling by PDGF
R-HSA-449147	Signaling by Interleukins
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 582 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GNF2_MSN, GOBP_GLAND_MORPHOGENESIS, GNF2_BNIP2, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_INTERLEUKIN_4

GO Biological Process (21): negative regulation of transcription by RNA polymerase II (GO:0000122), T-helper 1 cell lineage commitment (GO:0002296), negative regulation of type 2 immune response (GO:0002829), regulation of transcription by RNA polymerase II (GO:0006357), defense response (GO:0006952), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cytokine-mediated signaling pathway (GO:0019221), mammary gland epithelial cell proliferation (GO:0033598), interleukin-4-mediated signaling pathway (GO:0035771), regulation of cell population proliferation (GO:0042127), response to peptide hormone (GO:0043434), positive regulation of transcription by RNA polymerase II (GO:0045944), isotype switching to IgE isotypes (GO:0048289), positive regulation of isotype switching to IgE isotypes (GO:0048295), growth hormone receptor signaling pathway via JAK-STAT (GO:0060397), mammary gland morphogenesis (GO:0060443), regulation of mast cell proliferation (GO:0070666), positive regulation of cold-induced thermogenesis (GO:0120162), regulation of DNA-templated transcription (GO:0006355), signal transduction (GO:0007165), gene expression (GO:0010467)

GO Molecular Function (11): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), protein phosphatase binding (GO:0019903), identical protein binding (GO:0042802), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575), sperm head-tail coupling apparatus (GO:0120212)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Immune System	2
Signaling by PDGF	1
STING mediated induction of host immune responses	1
Signaling by Interleukins	1
Differentiation of T cells	1
Cytosolic sensors of pathogen-associated DNA	1
Innate Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Cytokine Signaling in Immune system	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
regulation of cellular process	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
T-helper cell lineage commitment	1
T-helper 1 cell differentiation	1
regulation of type 2 immune response	1
type 2 immune response	1
negative regulation of immune response	1
response to stress	1
cell surface receptor signaling pathway via STAT	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
epithelial cell proliferation	1
mammary gland epithelium development	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-4	1
cell population proliferation	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
positive regulation of DNA-templated transcription	1
isotype switching	1
positive regulation of isotype switching	1
isotype switching to IgE isotypes	1
regulation of isotype switching to IgE isotypes	1
growth hormone receptor signaling pathway	1
gland morphogenesis	1
mammary gland development	1
mast cell proliferation	1
regulation of leukocyte proliferation	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
DNA-templated transcription	1
regulation of gene expression	1

Protein interactions and networks

STRING

3144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAT6	IL4	P05112	995
STAT6	IL4R	P24394	968
STAT6	IL13	P35225	945
STAT6	JAK1	P23458	933
STAT6	NAB2	Q15742	931
STAT6	IL13RA1	P78552	906
STAT6	IRF4	Q15306	906
STAT6	GATA3	P23771	887
STAT6	JAK2	O60674	883
STAT6	STAT2	P52630	873
STAT6	NCOA1	Q15788	872
STAT6	SND1	Q7KZF4	870
STAT6	TBX21	Q9UL17	867
STAT6	IFNG	P01579	863
STAT6	IRF9	Q00978	860

IntAct

72 interactions, top by confidence:

A	B	Type	Score
rep	MTHFD1	psi-mi:“MI:0914”(association)	0.640
STAT6	IL4R	psi-mi:“MI:0914”(association)	0.640
STING1	STAT6	psi-mi:“MI:0915”(physical association)	0.630
STAT6	STING1	psi-mi:“MI:0915”(physical association)	0.630
STAT6	STING1	psi-mi:“MI:0914”(association)	0.630
STAT6	TBK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.580
NMI	STAT6	psi-mi:“MI:0915”(physical association)	0.570
STAT6	NMI	psi-mi:“MI:0915”(physical association)	0.570
STAT6	rep	psi-mi:“MI:0915”(physical association)	0.550
STAT6	STAT6	psi-mi:“MI:0915”(physical association)	0.520
STAT6	MAVS	psi-mi:“MI:0914”(association)	0.460
MAVS	STAT6	psi-mi:“MI:0914”(association)	0.460
	STAT6	psi-mi:“MI:0915”(physical association)	0.400
PARP14	STAT6	psi-mi:“MI:0915”(physical association)	0.400
STAT6	PLEC	psi-mi:“MI:0915”(physical association)	0.400
EP300	STAT6	psi-mi:“MI:0915”(physical association)	0.400
STAT6	CEBPZ	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (129): STAT6 (Affinity Capture-Western), PPARG (Affinity Capture-Western), STAT6 (Reconstituted Complex), EP300 (Affinity Capture-Western), STAT6 (Affinity Capture-Western), EP300 (Co-localization), STAT6 (Co-localization), KDM3A (Co-fractionation), STAT6 (Co-fractionation), STAT6 (Co-fractionation), STAT6 (Co-fractionation), TSTA3 (Co-fractionation), STAT6 (Affinity Capture-MS), STAT6 (Affinity Capture-MS), STAT6 (Biochemical Activity)

ESM2 similar proteins: A2RRU4, A2SXS5, A6QM06, F1LQY6, F1R7R1, O00255, O88559, P12755, P42226, P85299, P97260, Q0P5I0, Q0VF94, Q12770, Q17RQ9, Q2KJ58, Q3B7L5, Q3UHE1, Q496Y0, Q50H33, Q5MNU5, Q5SNT2, Q60698, Q66H91, Q68EN5, Q68FF6, Q69Z89, Q6GQT6, Q6NS60, Q6ZPY2, Q6ZWB6, Q76JQ2, Q80U28, Q80U62, Q8C190, Q8HXH0, Q8NFZ0, Q8QZS3, Q8TEK3, Q8WVT3

Diamond homologs: P42226, P42229, P42230, P42231, P42232, P51692, P52632, P52633, Q24151, Q61AP6, Q62771, Q7QDU4, Q95115, Q9TUM3, Q9TUZ0, Q9TUZ1, P40763, P42224, P42225, P42227, P42228, P52631, P61635, Q14765, Q19S50, Q6DV79, Q7ZXK3, Q9NAD6, Q9PVX8, Q764M5, O00910, Q54BD4, Q70GP4, O02799, P52630, Q9WVL2

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
MAPK8	down-regulates	STAT6	phosphorylation
TBK1	up-regulates	STAT6	phosphorylation
PTPN2	“down-regulates activity”	STAT6	dephosphorylation
JAK1	“up-regulates activity”	STAT6	phosphorylation
JAK2	“up-regulates activity”	STAT6	phosphorylation
STAT6	“up-regulates quantity by expression”	PPARG	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	PPARA	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	MRC1	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	RETN	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	CHI3L1	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	PPARGC1A	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	KDM6B	“transcriptional regulation”
STAT6	up-regulates	M2_polarization
STAT6	“down-regulates activity”	STAT1	binding
STAT6	“down-regulates activity”	NfKb-p65/p50	binding
STAT6	“up-regulates quantity by expression”	KLF4	“transcriptional regulation”
KLF4	up-regulates	STAT6
STAT6	“up-regulates quantity by expression”	SOCS1	“transcriptional regulation”
STAT6	up-regulates	ALOX15
STAT6	up-regulates	GATA3
STAT6	“up-regulates quantity by expression”	HSD3B2	“transcriptional regulation”
STAT6	“up-regulates quantity by expression”	SLC26A4	“transcriptional regulation”
PTPN1	“down-regulates activity”	STAT6	dephosphorylation
CBLB	“down-regulates quantity”	STAT6	ubiquitination
PTPN6	down-regulates	STAT6

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — DLBCLNOS, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	93
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2582687	NM_003153.5(STAT6):c.1256A>G (p.Asp419Gly)	Pathogenic
2582688	NM_003153.5(STAT6):c.1255G>T (p.Asp419Tyr)	Pathogenic
2582690	NM_003153.5(STAT6):c.1144G>C (p.Glu382Gln)	Pathogenic
2582691	NM_003153.5(STAT6):c.1555G>C (p.Asp519His)	Pathogenic
2582692	NM_003153.5(STAT6):c.1114G>A (p.Glu372Lys)	Pathogenic
2582689	NM_003153.5(STAT6):c.1255G>C (p.Asp419His)	Likely pathogenic

SpliceAI

3534 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57096990:C:CT	acceptor_gain	1.0000
12:57098765:C:CA	donor_gain	1.0000
12:57098770:T:A	donor_gain	1.0000
12:57098779:T:A	donor_gain	1.0000
12:57098790:A:AC	donor_gain	1.0000
12:57098791:C:CC	donor_gain	1.0000
12:57098791:CA:C	donor_gain	1.0000
12:57098798:T:C	donor_gain	1.0000
12:57099275:G:C	donor_gain	1.0000
12:57099292:A:AC	donor_gain	1.0000
12:57099293:C:CC	donor_gain	1.0000
12:57099293:CG:C	donor_gain	1.0000
12:57099319:AT:A	donor_gain	1.0000
12:57099320:T:TA	donor_gain	1.0000
12:57099765:ACCAT:A	donor_gain	1.0000
12:57099766:CCATC:C	donor_gain	1.0000
12:57099989:GACT:G	donor_loss	1.0000
12:57099990:ACTC:A	donor_loss	1.0000
12:57099991:CTCA:C	donor_loss	1.0000
12:57099992:TCA:T	donor_loss	1.0000
12:57099993:CAC:C	donor_loss	1.0000
12:57099994:A:AC	donor_gain	1.0000
12:57099994:ACC:A	donor_loss	1.0000
12:57099995:C:CC	donor_gain	1.0000
12:57099995:CCGGT:C	donor_gain	1.0000
12:57100088:CTC:C	acceptor_gain	1.0000
12:57100089:TC:T	acceptor_gain	1.0000
12:57100090:CC:C	acceptor_gain	1.0000
12:57100091:C:CC	acceptor_gain	1.0000
12:57102285:ATGAC:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000113180 (12:57099468 C>T), RS1000138612 (12:57112853 C>T), RS1000446839 (12:57101086 T>C), RS1000488507 (12:57105682 A>G), RS1000560421 (12:57101610 C>G,T), RS1000660641 (12:57096379 T>C), RS1000740804 (12:57111365 C>T), RS1000771736 (12:57107523 A>G), RS1001430880 (12:57112700 C>A), RS1001529800 (12:57109070 C>T), RS1001722505 (12:57106653 A>G), RS1001785910 (12:57100245 A>G), RS1001796467 (12:57095300 G>A), RS1001863412 (12:57110887 C>T), RS1001912456 (12:57095558 C>A,T)

Disease associations

OMIM: gene MIM:601512 | disease phenotypes: MIM:620532

GenCC curated gene-disease

Disease	Classification	Inheritance
hyper-IgE syndrome 6, autosomal dominant, with recurrent infections	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hyper-IgE syndrome 6, autosomal dominant, with recurrent infections	Strong	AD

Mondo (1): hyper-IgE syndrome 6, autosomal dominant, with recurrent infections (MONDO:0957807)

Orphanet (0):

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000016	Urinary retention
HP:0000290	Abnormal forehead morphology
HP:0000651	Diplopia
HP:0000939	Osteoporosis
HP:0001047	Atopic dermatitis
HP:0001581	Recurrent skin infections
HP:0001824	Weight loss
HP:0001880	Increased total eosinophil count
HP:0001943	Hypoglycemia
HP:0001945	Fever
HP:0001988	Recurrent hypoglycemia
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002099	Asthma
HP:0002205	Recurrent respiratory infections
HP:0002585	Abnormal peritoneum morphology
HP:0002664	Neoplasm
HP:0002896	Neoplasm of the liver
HP:0003212	Increased circulating IgE concentration
HP:0003419	Low back pain
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0004375	Neoplasm of the nervous system
HP:0004429	Recurrent viral infections
HP:0004912	Hypophosphatemic rickets
HP:0007185	Loss of consciousness
HP:0008775	Abnormal prostate morphology
HP:0010784	Uterine neoplasm
HP:0010787	Genital neoplasm

GWAS associations

59 associations (top):

Study	Trait	p-value
GCST000620_6	Eosinophilic esophagitis (pediatric)	2.000000e-06
GCST001316_2	IgE levels	2.000000e-12
GCST002084_10	Allergic sensitization	1.000000e-14
GCST002090_7	Sensory disturbances after bilateral sagittal split ramus osteotomy	7.000000e-06
GCST002539_15	Schizophrenia	2.000000e-12
GCST002697_4	Eosinophilic esophagitis	2.000000e-07
GCST003720_17	Migraine	1.000000e-09
GCST003720_20	Migraine	6.000000e-49
GCST003721_7	Migraine without aura	4.000000e-16
GCST003987_18	Asthma	1.000000e-10
GCST003990_25	Allergy	6.000000e-07
GCST004600_7	Eosinophil percentage of white cells	6.000000e-18
GCST004606_70	Eosinophil count	5.000000e-18
GCST004617_144	Eosinophil percentage of granulocytes	3.000000e-17
GCST004623_59	Neutrophil percentage of granulocytes	2.000000e-15
GCST004624_145	Sum eosinophil basophil counts	5.000000e-17
GCST004861_11	Itch intensity from mosquito bite	3.000000e-13
GCST004863_34	Mosquito bite size	2.000000e-08
GCST004864_10	Perceived unattractiveness to mosquitoes	1.000000e-06
GCST004865_9	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST005038_77	Allergic disease (asthma, hay fever or eczema)	1.000000e-22
GCST005212_34	Asthma	4.000000e-09
GCST005337_1	Headache	5.000000e-47
GCST006086_6	Familial lung cancer	1.000000e-06
GCST006408_5	Allergic sensitization	1.000000e-09
GCST006803_97	Schizophrenia	3.000000e-11
GCST006862_2	Asthma	6.000000e-09
GCST006911_24	Asthma (moderate or severe)	4.000000e-13
GCST007266_3	Adult asthma	9.000000e-07
GCST007563_7	Allergic disease (asthma, hay fever or eczema)	1.000000e-09

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005298	allergic sensitization measurement
EFO:0005324	post-operative sensory disturbance
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008380	perceived unattractiveness to mosquitos measurement
EFO:0006953	family history of lung cancer
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0009935	Non-steroidal anti-inflammatory and antirheumatic product use measurement
EFO:0009941	Inhalant adrenergic use measurement
EFO:0009943	Antihistamine use measurement
EFO:0010092	bitter alcoholic beverage consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523694 (PROTEIN-PROTEIN INTERACTION), CHEMBL5401 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 638,597 (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
CHEMBL1200916	THIORIDAZINE HYDROCHLORIDE	4	14,243
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	141,917
CHEMBL43	AMSACRINE	4	82,326
CHEMBL477	ADENOSINE	4	222,014
CHEMBL660	AMANTADINE	4	69,750
CHEMBL942	BISACODYL	4	14,654
CHEMBL50	QUERCETIN	3	74,559
CHEMBL84158	TIAPRIDE	3	3,518
CHEMBL22077	HYCANTHONE	2	2,210
CHEMBL417799	SANGUINARIUM	2	8,822
CHEMBL86754	IODOQUINOL	2	4,584

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1059513	Efficacy	3	esomeprazole	eosinophilic esophagitis

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs841718	STAT6		0.00	0
rs3024971	STAT6		0.00	0
rs167769	STAT6		0.00	0
rs1059513	NAB2, STAT6	3	2.25	1	esomeprazole
rs324011	STAT6		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — STAT transcription factors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 19a [PMID: 26506089]	Inhibition	7.55	pIC50

Binding affinities (BindingDB)

195 measured of 195 human assays (208 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-Amino-5-[2-[[4-[4- (dimethylcarbamoyl)phenyl]-1- piperidyl]methyl]-1-methyl- pyrrolo[2,3-b]pyridin-4-yl]benzoic acid	KD	9.05 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
Ethyl 6-amino-3-[2-[[4-[4- (dimethylcarbamoyl)phenyl]-1- piperidyl]methyl]-1-methyl- pyrrolo[2,3-b]pyridin-4-yl]pyridine-2- carboxylate	KD	11 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250325677, Example 3p1	KD	11.4 nM	US-20250325677: STAT6 DEGRADERS
4-[1-[[4-(6-Amino-3-pyridyl)-1- methyl-pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]-N,N-dimethyl- benzamide	KD	11.4 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
2-(2-Amino-5-(2-((4-(4- (dimethylcarbamoyl)phenyl)piperidin- 1-yl)methyl)-1-methyl-1H-pyrrolo[2,3- b]pyridin-4-yl)phenyl)-2-oxoacetic acid	KD	12.8 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af12	KD	12.9 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Aminopyridazin-3-yl)-1- methyl-pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]-N,N-dimethyl- benzamide	KD	13.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af8	KD	14.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af33	KD	15.4 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af16	KD	15.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af36	KD	15.7 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-Dimethyl-4-[1-[1-methyl-4-[6- (methylamino)-3-pyridyl]pyrrolo[2,3- b]pyridin-2-yl]methyl]-4- piperidyl]benzamide	KD	16 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N,3-Trimethyl-4-[1-[[1-methyl-4-[5- (methylamino)-1-oxido-pyridin-1-ium- 2-yl]pyrrolo[2,3-b]pyridin-2- yl]methyl]-3,6-dihydro-2H-pyridin-4- yl]benzamide	KD	16 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
2-[[5-[2-[[4-[4- (Dimethylcarbamoyl)phenyl]-1- piperidyl]methyl]-1-methyl- pyrrolo[2,3-b]pyridin-4-yl]-2- pyridyl]amino]acetic acid	KD	16.3 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-[6-(2-Hydroxyethylamino)-3- pyridyl]-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-dimethyl-benzamide	KD	16.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
Methyl 2-[[5-[2-[[4-[4- (dimethylcarbamoyl)phenyl]-1- piperidyl]methyl]-1-methyl- pyrrolo[2,3-b]pyridin-4-yl]-2- pyridyl]amino]acetate	KD	16.8 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-Dimethyl-4-[(2R,4R)-1-[[4-(5- amino-2-pyridyl)-1-methyl- pyrrolo[2,3-b]pyridin-2-yl]methyl]-2- methyl-4-piperidyl]benzamide and N,N-dimethyl-4-[(2S,4S)-1-[[4-(5- amino-2-pyridyl)-1-methyl- pyrrolo[2,3-b]pyridin-2-yl]methyl]-2- methyl-4-piperidyl]benzamide	KD	18.1 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-Dimethyl-4-[(2R,4R)-1-[[4-(6- amino-2-cyano-3-pyridyl)-1-methyl- pyrrolo[2,3-b]pyridin-2-yl]methyl]-2- methyl-4-piperidyl]benzamide and N,N-dimethyl-4-[(2S,4S)-1-[[4-(6- amino-2-cyano-3-pyridyl)-1-methyl- pyrrolo[2,3-b]pyridin-2-yl]methyl]-2- methyl-4-piperidyl]benzamide	KD	18.4 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af14	KD	18.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af34	KD	18.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-(1-((4-(5-Aminopyridin-2-yl)-1- methyl-1H-pyrrolo[2,3-b]pyridin-2- yl)methyl)piperidin-4-yl)-N,N- dimethylbenzamide	KD	18.8 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N,3-Trimethyl-4-[4-[[1-methyl-4-[6- (methylamino)pyridazin-3- yl]pyrrolo[2,3-b]pyridin-2- yl]methyl]piperazin-1-yl]benzamide	KD	19.2 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af26	KD	20 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-2-methyl-3- pyridyl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-dimethyl-benzamide	KD	20.1 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1s28	KD	20.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af45	KD	21.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N,3-Trimethyl-4-[1-[[1-methyl-4-[6- (methylamino)pyridazin-3- yl]pyrrolo[2,3-b]pyridin-2-yl]methyl]- 3,6-dihydro-2H-pyridin-4- yl]benzamide	KD	22 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
3-Fluoro-N,N-dimethyl-4-(1-((1- methyl-4-(6-(methylamino)pyridin-3- yl)-1H-pyrrolo[2,3-b]pyridin-2- yl)methyl)piperidin-4-yl)benzamide	KD	22.1 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-2-methoxy-3- pyridyl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-dimethyl-benzamide	KD	22.3 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-dimethyl-4-(1-(1-(1-methyl-4-(6- (methylamino)pyridin-3-yl)-1H- pyrrolo[2,3-b]pyridin-2- yl)ethyl)piperidin-4-yl)benzamide	KD	22.3 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-(1-((4-(6-aminopyridin-3-yl)-1- methyl-1H-pyrrolo[2,3-b]pyridin-2- yl)methyl)piperidin-4-yl)-N,N- dimethylbenzamide	KD	22.3 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-4-fluoro-3-pyridyl)- 1-methyl-pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]-N,N- bis(trideuteriomethyl)benzamide	KD	22.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-Dimethyl-4-[1-[[1-methyl-4-[6- (methylamino)pyridazin-3- yl]pyrrolo[2,3-b]pyridin-2-yl]methyl]- 4-piperidyl]benzamide	KD	22.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-Dimethyl-4-[(4R)-1-[[1-methyl-4- [6-(methylamino)-3- pyridyl]pyrrolo[2,3-b]pyridin-2- yl]methyl]-2-oxo-4- piperidyl]benzamide and N,N- dimethyl-4-[(4S)-1-[[1-methyl-4-[6- (methylamino)-3-pyridyl]pyrrolo[2,3- b]pyridin-2-yl]methyl]-2-oxo-4- piperidyl]benzamide	KD	23.2 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(5-Amino-1-oxido-pyridin-1- ium-2-yl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-dimethyl-benzamide	KD	23.9 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af30	KD	24.1 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
(R)-N,N-Dimethyl-4-[1-[[4-(6-amino- 3-pyridyl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-2-oxo-4- piperidyl]benzamide and (S)-N,N- dimethyl-4-[1-[[4-(6-amino-3-pyridyl)- 1-methyl-pyrrolo[2,3-b]pyridin-2- yl]methyl]-2-oxo-4- piperidyl]benzamide	KD	24.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(5-Amino-2-pyridyl)-1- methyl-pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]-N,N- bis(trideuteriomethyl)benzamide	KD	25.4 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-2-methoxy-3- pyridyl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-bis(trideuteriomethyl)benzamide	KD	25.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-2-methoxy-3- pyridyl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-bis(trideuteriomethyl)benzamide	KD	25.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[1-Methyl-4-[6-(methylamino)- 3-pyridyl]pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]-N,N- bis(trideuteriomethyl)benzamide	KD	27.7 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-2-cyano-3-pyridyl)- 1-(trideuteriomethyl)pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-dimethyl-benzamide	KD	27.7 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N,3,5-Tetramethyl-4-[1-[[1-methyl- 4-[6-(methylamino)-3- pyridyl]pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]benzamide	KD	28.8 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N,3-Trimethyl-4-[4-[[1-methyl-4-[6- (methylamino)-3-pyridyl]pyrrolo[2,3- b]pyridin-2-yl]methyl]piperazin-1- yl]benzamide	KD	28.9 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
N,N-Dimethyl-4-[1-[[4-[6- (methylamino)-3-pyridyl]-1- methylsulfonyl-pyrrolo[2,3-b]pyridin- 2-yl]methyl]-4-piperidyl]benzamide	KD	29.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-5-methyl-3- pyridyl)-1-methyl-pyrrolo[2,3- b]pyridin-2-yl]methyl]-4-piperidyl]- N,N-dimethyl-benzamide	KD	30.5 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
3-Fluoro-N,N-dimethyl-4-[1-[[1- methyl-4-[5-(methylamino)-2- pyridyl]pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]benzamide	KD	30.6 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
(S)-N,N-dimethyl-4-(1-(1-(1-methyl-4- (5-(methylamino)pyridin-2-yl)-1H- pyrrolo[2,3-b]pyridin-2- yl)ethyl)piperidin-4-yl)benzamide and (R)-N,N-dimethyl-4-(1-(1-(1-methyl-4- (5-(methyl-amino)pyridin-2-yl)-1H- pyrrolo[2,3-b]pyridin-2- yl)ethyl)piperidin-4-yl)benzamide	KD	31.2 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
US20250340551, Example 1af18	KD	31.4 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6
4-[1-[[4-(6-Amino-2-cyano-3-pyridyl)- 1-methyl-pyrrolo[2,3-b]pyridin-2- yl]methyl]-4-piperidyl]-N,N-dimethyl- benzamide	KD	31.4 nM	US-20250340551: SMALL MOLECULE MODULATORS OF STAT6

ChEMBL bioactivities

312 potent at pChembl≥5 of 468 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.15	IC50	0.7	nM	CHEMBL487451
9.15	IC50	0.7	nM	CHEMBL593171
8.85	IC50	1.4	nM	CHEMBL470963
8.80	IC50	1.6	nM	CHEMBL488814
8.74	IC50	1.8	nM	CHEMBL519249
8.74	IC50	1.8	nM	CHEMBL512874
8.72	IC50	1.9	nM	CHEMBL595058
8.68	IC50	2.1	nM	CHEMBL529443
8.66	IC50	2.2	nM	CHEMBL519410
8.49	IC50	3.2	nM	CHEMBL596420
8.33	IC50	4.7	nM	CHEMBL606350
8.26	IC50	5.5	nM	CHEMBL487450
8.25	IC50	5.6	nM	CHEMBL596421
8.22	Ki	6	nM	CHEMBL6169609
8.22	Ki	6	nM	CHEMBL6148327
8.22	Ki	6	nM	CHEMBL6169593
8.21	IC50	6.2	nM	CHEMBL470949
8.20	Potency	6.3	nM	CHEMBL1380504
8.19	IC50	6.5	nM	CHEMBL471114
8.15	IC50	7	nM	CHEMBL471113
8.10	IC50	7.9	nM	CHEMBL471131
8.09	IC50	8.2	nM	CHEMBL469910
8.00	Ki	10	nM	CHEMBL6132917
8.00	Ki	10	nM	CHEMBL6146875
7.96	IC50	11	nM	CHEMBL512533
7.92	IC50	12	nM	CHEMBL594344
7.90	Potency	12.6	nM	CHEMBL1544947
7.80	IC50	16	nM	CHEMBL517122
7.77	IC50	17	nM	CHEMBL513401
7.72	IC50	19	nM	CHEMBL487460
7.70	IC50	20	nM	CHEMBL5280678
7.68	IC50	21	nM	CHEMBL228192
7.66	IC50	22	nM	CHEMBL471130
7.64	IC50	23	nM	CHEMBL486643
7.60	IC50	25	nM	CHEMBL471743
7.60	IC50	25	nM	CHEMBL512519
7.58	IC50	26	nM	CHEMBL595488
7.55	IC50	28	nM	CHEMBL3741938
7.52	IC50	30	nM	CHEMBL226930
7.48	Ki	33	nM	CHEMBL6142401
7.47	IC50	34	nM	CHEMBL594821
7.44	IC50	36	nM	CHEMBL471559
7.43	IC50	37	nM	CHEMBL603203
7.42	IC50	38	nM	CHEMBL520234
7.38	Ki	42	nM	CHEMBL6169635
7.36	IC50	44	nM	CHEMBL3741162
7.35	IC50	45	nM	CHEMBL228018
7.30	IC50	50	nM	CHEMBL5410106
7.25	IC50	56	nM	CHEMBL5267203
7.24	Ki	57	nM	CHEMBL6152739

PubChem BioAssay actives

145 with measured affinity, of 236 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
2-(4-morpholin-4-ylanilino)-4-[(2,3,6-trifluorophenyl)methylamino]pyrimidine-5-carboxamide	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0007	uM
2-(4-morpholin-4-ylanilino)-4-[(2,4,6-trifluorophenyl)methylamino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0007	uM
4-[(2-fluorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0014	uM
4-[(2,5-difluorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0016	uM
2-(4-morpholin-4-ylanilino)-4-[(2,3,5-trifluorophenyl)methylamino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0018	uM
4-[(3-fluorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0018	uM
2-[4-[4-[[7-[(3,5-difluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]acetamide	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0019	uM
4-[(2,3-difluorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0021	uM
4-[(2,6-difluorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0022	uM
7-[(3,5-difluorophenyl)methyl]-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-2-amine	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0032	uM
2-[4-[4-[[7-[(3,5-difluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]-N-methylacetamide	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0047	uM
4-[(3,5-difluorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0055	uM
2-[4-[4-[[9-[(3,5-difluorophenyl)methyl]purin-2-yl]amino]phenyl]piperazin-1-yl]ethanol	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0056	uM
4-(benzylamino)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0062	uM
4-(benzylamino)-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0065	uM
4-(benzylamino)-2-(4-piperazin-1-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0070	uM
4-[(2-chlorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0079	uM
4-[(2-methoxyphenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0082	uM
4-[(2-methylphenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0110	uM
7-[(3,5-difluorophenyl)methyl]-N-(4-piperazin-1-ylphenyl)pyrrolo[2,3-d]pyrimidin-2-amine	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0120	uM
4-(benzylamino)-2-[4-(4-hydroxypiperidin-1-yl)anilino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0160	uM
4-(benzylamino)-2-[4-(1-methylpiperidin-4-yl)anilino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0170	uM
4-[(3-hydroxyphenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0190	uM
(5R,6S,9E)-16-chloro-13,15-dihydroxy-5,6,10-trimethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1954728: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs by Promega reporter rene assay	ic50	0.0200	uM
4-(benzylamino)-2-[2-(3-chloro-4-hydroxyphenyl)ethylamino]pyrimidine-5-carboxamide	284275: Inhibition of STAT6 in human IL4-stimulated FW4 cells	ic50	0.0210	uM
4-[(2-hydroxyphenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0220	uM
4-[(2-methylsulfanylphenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0230	uM
4-[(3-methoxyphenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0250	uM
2-(4-morpholin-4-ylanilino)-4-[[2-(trifluoromethyl)phenyl]methylamino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0250	uM
2-[4-[4-[[7-[(3,5-difluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]acetic acid	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0260	uM
[4-[(E)-4-[[(2S)-1-[(2S)-2-[(4-iodophenyl)-phenylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-4-oxobut-2-en-2-yl]phenyl] dihydrogen phosphate	1264595: Inhibition of STAT6 (unknown origin) expressed in Escherichia coli using FAM-Ala-pTyr-Lys-ProPhe-Gln-Asp-Leu-Ile-NH2 as substrate by fluorescence polarization assay	ic50	0.0280	uM
4-(benzylamino)-2-[2-(3-chloro-4-hydroxyphenyl)ethylamino]-N-methylpyrimidine-5-carboxamide	284275: Inhibition of STAT6 in human IL4-stimulated FW4 cells	ic50	0.0300	uM
N-[4-[4-(2-aminoethyl)piperazin-1-yl]phenyl]-7-[(3,5-difluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-2-amine	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0340	uM
4-[(3-chlorophenyl)methylamino]-2-(4-morpholin-4-ylanilino)pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0360	uM
7-[(3-fluorophenyl)methyl]-N-(4-morpholin-4-ylphenyl)pyrrolo[2,3-d]pyrimidin-2-amine	452105: Inhibition of STAT6 in IL4-stimulated human FW4 reporter cells by luciferase assay	ic50	0.0370	uM
2-(4-morpholin-4-ylanilino)-4-[(2-nitrophenyl)methylamino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0380	uM
[4-[(E)-3-[[(2S)-1-[(2S)-2-[(4-iodophenyl)-phenylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-3-oxoprop-1-enyl]phenyl] dihydrogen phosphate	1264595: Inhibition of STAT6 (unknown origin) expressed in Escherichia coli using FAM-Ala-pTyr-Lys-ProPhe-Gln-Asp-Leu-Ile-NH2 as substrate by fluorescence polarization assay	ic50	0.0440	uM
2-[2-(3-chloro-4-hydroxyphenyl)ethylamino]-4-(3-methylanilino)pyrimidine-5-carboxamide	284275: Inhibition of STAT6 in human IL4-stimulated FW4 cells	ic50	0.0450	uM
(5R,6S,7S,9E)-16-chloro-7,13,15-trihydroxy-5,6,10-trimethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1985589: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs	ic50	0.0500	uM
(5R,6S,7R,9E)-16-chloro-7,13,15-trihydroxy-5,6,10-trimethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1954728: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs by Promega reporter rene assay	ic50	0.0560	uM
4-(benzylamino)-2-[2-(3,5-dichloro-4-hydroxyphenyl)ethylamino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0610	uM
(5R,6S,7S,9Z)-16-chloro-7,13,15-trihydroxy-5,6,10-trimethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1985589: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs	ic50	0.0640	uM
2-[2-(3-fluoro-4-hydroxyphenyl)ethylamino]-4-(3-methylanilino)pyrimidine-5-carboxamide	284275: Inhibition of STAT6 in human IL4-stimulated FW4 cells	ic50	0.0640	uM
(9E)-16-chloro-6,13,15-trihydroxy-5,6,10-trimethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1954728: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs by Promega reporter rene assay	ic50	0.0680	uM
(5R,6S,7R,9Z)-16-chloro-7,13,15-trihydroxy-5,6,10-trimethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1985589: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs	ic50	0.0720	uM
(9E)-16-chloro-13,15-dihydroxy-5,6,6,10-tetramethyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione	1954728: Inhibition of IL-4 induced STAT6 signaling in human HepG2 cells harboring pRL-EF1alpha, pGL3-TK-7xN4 and TOPO-Stat6 plasmid assessed as luciferase activity incubated for 24 hrs by Promega reporter rene assay	ic50	0.0790	uM
4-(benzylamino)-2-[4-(3-hydroxypropyl)anilino]pyrimidine-5-carboxamide	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0810	uM
2-[2-(3-bromo-4-hydroxyphenyl)ethylamino]-4-(3-methylanilino)pyrimidine-5-carboxamide	284275: Inhibition of STAT6 in human IL4-stimulated FW4 cells	ic50	0.0830	uM
4-(benzylamino)-2-[2-(4-hydroxyphenyl)ethylamino]pyrimidine-5-carboxamide	284275: Inhibition of STAT6 in human IL4-stimulated FW4 cells	ic50	0.0880	uM
2-(4-morpholin-4-ylanilino)-4-[(2,4,6-trifluorophenyl)methylamino]pyrimidine-5-carboxamide;hydrochloride	343057: Inhibition of STAT6 activation in FW4 reporter cells	ic50	0.0880	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
bisphenol A	decreases expression, increases expression, increases phosphorylation	3
trichostatin A	increases expression, affects cotreatment	3
Air Pollutants	affects expression, decreases expression, affects cotreatment, increases abundance, increases oxidation	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Vehicle Emissions	increases expression, decreases expression, increases abundance, affects cotreatment	2
Cisplatin	decreases phosphorylation, affects cotreatment, increases expression	2
Lead	decreases expression	2
Ozone	increases abundance, affects expression, affects cotreatment, increases oxidation	2
Plant Extracts	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Dronabinol	increases phosphorylation, decreases reaction, affects reaction, increases expression	2
Tretinoin	increases expression	2
alpinumisoflavone	decreases activity, decreases phosphorylation	1
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
geraniol	increases expression	1
acetylsalicylic acid lysinate	affects reaction, increases activity, decreases reaction, increases phosphorylation	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
isoquercitrin	increases expression	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

81 unique, capped per target: 77 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4356752	Binding	Protac activity at CRBN/STAT6 in human MOLM16 cells assessed as degradation of STAT6 at 0.01 to 10 uM incubated for 4 hrs by Western blot analysis	Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein. — J Med Chem
CHEMBL4715506	Functional	In vivo protac activity at CRBN/STAT6 degradation in SCID mouse xenografted with human MOLM16 cells assessed as reduction in STAT6 in tumor tissue at 50 mg/kg, iv measured after 24 hrs by immunoblotting analysis	SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression. — ACS Med Chem Lett

Cellosaurus cell lines

15 cell lines: 12 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8BY	HEK-Blue STAT6-hSTING-R232	Transformed cell line	Female
CVCL_A8DA	HEK-Blue IL-4/IL-13	Transformed cell line	Female
CVCL_B8QC	Abcam HCT 116 STAT6 KO	Cancer cell line	Male
CVCL_B9C0	Abcam MCF-7 STAT6 KO	Cancer cell line	Female
CVCL_B9ST	Abcam A-549 STAT6 KO	Cancer cell line	Male
CVCL_C6JI	SFT-T1	Cancer cell line	Male
CVCL_C6JJ	SFT-T2	Cancer cell line	Female
CVCL_D4AC	SFT-S1	Cancer cell line	Female
CVCL_D8BP	Ubigene A-549 STAT6 KO	Cancer cell line	Male
CVCL_D8WI	Ubigene HCT 116 STAT6 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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