TAB1

Summary

TAB1 (TGF-beta activated kinase 1 (MAP3K7) binding protein 1, HGNC:18157) is a protein-coding gene on chromosome 22q13.1, encoding TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (Q15750). Key adapter protein that plays an essential role in JNK and NF-kappa-B activation and proinflammatory cytokines production in response to stimulation with TLRs and cytokines.

The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such as those induced by TGF beta, interleukin 1, and WNT-1. This protein interacts and thus activates TAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents an alternative activation pathway, in addition to the MAPKK pathways, which contributes to the biological responses of MAPK14 to various stimuli. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 10454 — RefSeq curated summary.

At a glance

• GWAS associations: 41
• Clinical variants (ClinVar): 82 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18157
Approved symbol	TAB1
Name	TGF-beta activated kinase 1 (MAP3K7) binding protein 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100324
Ensembl biotype	protein_coding
OMIM	602615
Entrez	10454

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000216160, ENST00000331454, ENST00000461775, ENST00000473491, ENST00000473613, ENST00000488859, ENST00000490819, ENST00000869604, ENST00000869605, ENST00000932145, ENST00000943654

RefSeq mRNA: 2 — MANE Select: NM_006116 NM_006116, NM_153497

CCDS: CCDS13992, CCDS13993

Canonical transcript exons

ENST00000216160 — 11 exons

Exon	Start	End
ENSE00000654726	39416791	39416877
ENSE00000654728	39417711	39417849
ENSE00000654729	39418732	39418845
ENSE00000654730	39419519	39419630
ENSE00000654731	39421827	39421971
ENSE00000654734	39428021	39428183
ENSE00000880355	39415006	39415142
ENSE00001109364	39430015	39431882
ENSE00001313059	39399780	39399835
ENSE00003511483	39415500	39415653
ENSE00003634964	39426703	39426925

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 93.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5166 / max 63.9050, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192340	13.5166	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	93.03	silver quality
vena cava	UBERON:0004087	91.51	silver quality
lateral nuclear group of thalamus	UBERON:0002736	91.15	silver quality
ventricular zone	UBERON:0003053	90.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.85	gold quality
cerebellar hemisphere	UBERON:0002245	90.63	gold quality
cerebellar cortex	UBERON:0002129	90.56	gold quality
sural nerve	UBERON:0015488	90.04	gold quality
apex of heart	UBERON:0002098	89.92	gold quality
cerebellum	UBERON:0002037	88.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.85	silver quality
right frontal lobe	UBERON:0002810	88.41	gold quality
subthalamic nucleus	UBERON:0001906	88.37	silver quality
nerve	UBERON:0001021	88.28	gold quality
tibial nerve	UBERON:0001323	88.28	gold quality
heart right ventricle	UBERON:0002080	88.18	silver quality
granulocyte	CL:0000094	88.12	gold quality
right ovary	UBERON:0002118	88.06	gold quality
lower esophagus	UBERON:0013473	88.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.02	gold quality
nucleus accumbens	UBERON:0001882	87.96	gold quality
lateral globus pallidus	UBERON:0002476	87.95	silver quality
ganglionic eminence	UBERON:0004023	87.95	gold quality
pons	UBERON:0000988	87.93	silver quality
pharyngeal mucosa	UBERON:0000355	87.86	silver quality
amygdala	UBERON:0001876	87.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.75	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.74	silver quality
muscle layer of sigmoid colon	UBERON:0035805	87.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HR, NFKB, NR2C2

miRNA regulators (miRDB)

24 targeting TAB1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-6508-3P	96.73	65.48	576

Literature-anchored findings (GeneRIF, showing 31)

• interaction with p38alpha leads to autophosphorylation and activation of p38alpha (PMID:11847341)
• The TAK1-TAB1 fusion protein is a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-kappaB signaling pathways (PMID:12372426)
• TauAlphaBeta1beta is involved in regulating p38alpha activity in physiological conditions (PMID:12429732)
• These results suggest that the TAK1-NLK MAPK cascade is activated by the noncanonical Wnt-5a/Ca(2+) pathway and antagonizes canonical Wnt/beta-catenin signaling. (PMID:12482967)
• characterized the molecular mechanisms of cellular stress-induced TAK1 activation, focusing mainly on the phosphorylation of TAK1 at Thr-187 and Ser-192 in the activation loop; TAB1 and TAB2 were differentially involved in the phosphorylation of TAK1 (PMID:15590691)
• Determinants that control the specific interactions between TAB1 and MAPK14 are identified. (PMID:16648477)
• The protein phosphatase 2C alpha fold is conserved in TAB1(a TAK1 regulatory subunit) but some AAs needed for dual metal-binding & catalysis are missing. It is a pseudophosphatase, & may bind/regulate access to phosphorylated AAs on downstream substrates. (PMID:16879102)
• a TAB1:TAK1:IKK beta:NF-kappaB signaling axis forms aberrantly in breast cancer cells and, consequently, enables oncogenic signaling by TGF-beta (PMID:18316610)
• TAB4 binds TAK1 and polyubiquitin chains to promote specific sites of phosphorylation in TAK1-TAB1, which activates IKK signaling to NF-kappaB. (PMID:18456659)
• periostin is involved in the suppression of cell invasiveness via the TAB1/TAK1 signaling pathway. (PMID:19578758)
• Co-expression of TAK1 and TAB1 resulted in a functional and active TAK1-TAB1 complex capable of directly activating full-length heterotrimeric mammalian AMP-activated protein kinase (AMPK) in vitro. (PMID:20538596)
• Phosphorylation and polyubiquitination of TAK1 are necessary for activation of NF-kappaB by the Kaposi’s sarcoma-associated herpesvirus vGPCR. (PMID:21159881)
• data suggest a complex role of aa 452-457 of TAB1 in controlling p38 MAPK activity and subcellular localization and implicate these residues in TAK1- or p38 MAPK-dependent post-transcriptional control of gene expression (PMID:22216226)
• TAK1 plays a critical role in accentuated epithelial to mesenchymal transition in obliterative bronchiolitis after lung transplantation. (PMID:22525462)
• We found that endothelial TAK1 and TAB2, but not TAB1, were critically involved in vascular formation (PMID:22972987)
• USP18 inhibits NF-kappaB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex. (PMID:23825189)
• The amino acid sequence between positions 373 and 502 of TAB1 is required for TP interaction. (PMID:24462677)
• Data indicate that mitogen-activated protein kinase (MAPK) p38 activation is triggered by AMP-activated protein kinases (AMPK) and mediated by TAB1 protein. (PMID:25151490)
• miR-29a repressed TAB1-mediated TIMP-1 production in dermal fibroblasts, demonstrating that miR-29a may be a therapeutic target in SSc. (PMID:25549087)
• TAK1/TAB1 expression in non-small cell lung carcinoma tissue is significantly increased and closely associated with patient clinical prognosis. (PMID:26884850)
• we show that IL-1 induces robust p38a activation both in the nucleus and in the cytoplasm/membrane.Following stimulation, p38a activity returns to a basal level in absence of receptor degradation. While nuclear pulse is controlled by MKP1 through a negative feedback to pp38, its basal activity is controlled by both TAB1 and MKP1 through a positive feedback loop. (PMID:27314954)
• TAB1 was identified as a functional target of miR-134, and the expression of TAB1 was increased by the transcription factors of NF-kappaB1, c-Rel, and ELK1 via miR-134. (PMID:28206956)
• Based on the crystal structure of the p38alpha-TAB1 complex authors replaced threonine 185 of p38alpha with glycine (T185G) to prevent an intramolecular hydrogen bond with Asp150 from being formed. This mutation did not interfere with TAB1 binding to p38alpha. (PMID:29229647)
• High TAB1 expression is associated with colorectal cancer. (PMID:29328486)
• Silencing of TAB1, but not TAK1, prevented p38MAPK activation, which is indicative of TAB1-mediated autophosphorylation of p38MAPK (PMID:29893818)
• multiple GPCR agonists utilize non-canonical TAB1-TAB2 and TAB1-TAB3-dependent p38 activation to promote endothelial inflammatory responses. (PMID:30760523)
• the present results indicated that miR889 inhibits the aggressive behaviors of nonsmall cell lung cancer (NSCLC) by directly targeting TAB1 mRNA, thus highlighting the importance of the miR889/TAB1 pathway in the malignant progression of NSCLC. (PMID:31115539)
• Myeloma cells self-promote migration by regulating TAB1-driven TIMP-1 expression in mesenchymal stem cells. (PMID:33183761)
• Chlamydia trachomatis antigen induces TLR4-TAB1-mediated inflammation, but not cell death, in maternal decidua cells. (PMID:36495029)
• Induction of pro-inflammatory genes by fibronectin DAMPs in three fibroblast cell lines: Role of TAK1 and MAP kinases. (PMID:37228128)
• Down-regulated TAB1 suppresses the replication of Coxsackievirus B5 via activating the NF-kappaB pathways through interaction with viral 3D polymerase. (PMID:38072991)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tab1	ENSDARG00000036613
mus_musculus	Tab1	ENSMUSG00000022414
rattus_norvegicus	Tab1	ENSRNOG00000017285
drosophila_melanogaster	Pdp	FBGN0029958
caenorhabditis_elegans	pdp-1	WBGENE00022832

Paralogs (16): PPM1F (ENSG00000100034), PPM1A (ENSG00000100614), PPM1H (ENSG00000111110), PPM1G (ENSG00000115241), ILKAP (ENSG00000132323), PPM1B (ENSG00000138032), PPM1J (ENSG00000155367), PPM1L (ENSG00000163590), PPM1K (ENSG00000163644), PPM1M (ENSG00000164088), PDP1 (ENSG00000164951), PPM1D (ENSG00000170836), PDP2 (ENSG00000172840), PPM1E (ENSG00000175175), PP2D1 (ENSG00000183977), PPM1N (ENSG00000213889)

Protein

Protein identifiers

TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 — Q15750 (reviewed: Q15750)

Alternative names: Mitogen-activated protein kinase kinase kinase 7-interacting protein 1, TGF-beta-activated kinase 1-binding protein 1

All UniProt accessions (2): Q15750, A8K6K3

UniProt curated annotations — full annotation on UniProt →

Function. Key adapter protein that plays an essential role in JNK and NF-kappa-B activation and proinflammatory cytokines production in response to stimulation with TLRs and cytokines. Mechanistically, associates with the catalytic domain of MAP3K7/TAK1 to trigger MAP3K7/TAK1 autophosphorylation leading to its full activation. Similarly, associates with MAPK14 and triggers its autophosphorylation and subsequent activation. In turn, MAPK14 phosphorylates TAB1 and inhibits MAP3K7/TAK1 activation in a feedback control mechanism. Also plays a role in recruiting MAPK14 to the TAK1 complex for the phosphorylation of the TAB2 and TAB3 regulatory subunits.

Subunit / interactions. Interacts with XIAP and BIRC7. Interacts with TRAF6 and MAP3K7; during IL-1 signaling. Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2. Interacts with TRAF6 and MAPK14; these interactions allow MAPK14 autophosphorylation. Interacts with STING1; interaction takes place following cGAMP activation and promotes TAB1 recruitment to the endoplasmic reticulum, triggering MAP3K7/TAK1 activation and STING1 phosphorylation.

Subcellular location. Cytoplasm. Cytosol. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated at all three sites Ser-423, Thr-431 and Ser-438 by MAPK14 when cells were exposed to cellular stresses, or stimulated with TNF, IL1 or LPS. These phosphorylations inhibit TAK1 activation by a feedback control mechanism. Dephosphorylated by DUSP14 at Ser-438, leading to TAB1-MAP3K7/TAK1 complex inactivation in T-cells. Ubiquitinated by MAP3K1 with ‘Lys-63’-linked polyubiquitin; leading to activation of TAK1 and of JNK and p38 MAP kinases following EGF and TGF-beta stimulation. Ubiquitinated by ITCH with ‘Lys-48’-linked polyubiquitin; leading to proteasomal degradation. Ubiquitinated by RNF114 during maternal-to-zygotic transition; leading to degradation. (Microbial infection) Deubiquitinated by Y.enterocolitica YopP. O-GlcNAcylated at Ser-395 by OGT is required for full MAP3K7/TAK1 activation upon stimulation with IL-1 or osmotic stress. Deglycosylated at Ser-395 by OGA.

Miscellaneous. Does not bind nor activate MAP3K7/TAK1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15750-1	1, TAB1alpha	yes
Q15750-2	2, TAB1beta

RefSeq proteins (2): NP_006107, NP_705717 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001932	PPM-type_phosphatase-like_dom	Domain
IPR015655	PP2C	Family
IPR036457	PPM-type-like_dom_sf	Homologous_superfamily

Pfam: PF00481

UniProt features (62 total): strand 21, helix 14, modified residue 6, mutagenesis site 6, turn 4, compositionally biased region 3, region of interest 2, chain 1, domain 1, glycosylation site 1, splice variant 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7NTH	X-RAY DIFFRACTION	1.97
7NTI	X-RAY DIFFRACTION	1.98
5JGA	X-RAY DIFFRACTION	2
5V5N	X-RAY DIFFRACTION	2.01
8GW3	X-RAY DIFFRACTION	2.05
5DIY	X-RAY DIFFRACTION	2.06
5E7R	X-RAY DIFFRACTION	2.11
4GS6	X-RAY DIFFRACTION	2.2
2J4O	X-RAY DIFFRACTION	2.25
2POM	X-RAY DIFFRACTION	2.27
5JH6	X-RAY DIFFRACTION	2.37
5J7S	X-RAY DIFFRACTION	2.37
5JK3	X-RAY DIFFRACTION	2.37
4O91	X-RAY DIFFRACTION	2.39
9FPD	X-RAY DIFFRACTION	2.4
5J8I	X-RAY DIFFRACTION	2.4
2YIY	X-RAY DIFFRACTION	2.49
5O90	X-RAY DIFFRACTION	2.49
4L52	X-RAY DIFFRACTION	2.54
2YDS	X-RAY DIFFRACTION	2.55
4L53	X-RAY DIFFRACTION	2.55
5NZZ	X-RAY DIFFRACTION	2.6
5GJG	X-RAY DIFFRACTION	2.61
4L3P	X-RAY DIFFRACTION	2.68
5VVU	X-RAY DIFFRACTION	2.7
4KA3	X-RAY DIFFRACTION	2.71
5J9L	X-RAY DIFFRACTION	2.75
5GJD	X-RAY DIFFRACTION	2.79
5JGB	X-RAY DIFFRACTION	2.8
5GJF	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15750-F1	78.82	0.60

Functional residue map

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

Catalytic / active sites (1): 484 (required for interaction with map3k7)

Post-translational modifications (6): 423, 431, 438, 442, 7, 378

Glycosylation sites (1): 395

Mutagenesis-validated functional residues (6):

Position	Phenotype
148	complete loss of itch-mediated ubiquitination.
213	loss of interaction with xiap.
216	loss of interaction with xiap.
395	about 50% loss of il-6 secretion after il-1alpha stimulation.
438	loss of phosphorylation site.
484	abolishes interaction with map3k7.

Function

Pathways and Gene Ontology

Reactome pathways

53 pathways

ID	Pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5689880	Ub-specific processing proteases
R-HSA-9014325	TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-9020702	Interleukin-1 signaling
R-HSA-937042	IRAK2 mediated activation of TAK1 complex
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-9645460	Alpha-protein kinase 1 signaling pathway
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975163	IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 224 (showing top): REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, PID_IL1_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (17): in utero embryonic development (GO:0001701), heart morphogenesis (GO:0003007), cardiac septum development (GO:0003279), signal transduction (GO:0007165), transforming growth factor beta receptor signaling pathway (GO:0007179), lung development (GO:0030324), aorta development (GO:0035904), non-canonical NF-kappaB signal transduction (GO:0038061), positive regulation of MAPK cascade (GO:0043410), coronary vasculature development (GO:0060976), positive regulation of cGAS/STING signaling pathway (GO:0141111), protein dephosphorylation (GO:0006470), canonical NF-kappaB signal transduction (GO:0007249), positive regulation of type I interferon production (GO:0032481), protein exit from endoplasmic reticulum (GO:0032527), cGAS/STING signaling pathway (GO:0140896), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (8): protein serine/threonine phosphatase activity (GO:0004722), protein serine/threonine kinase activator activity (GO:0043539), protein-containing complex binding (GO:0044877), mitogen-activated protein kinase p38 binding (GO:0048273), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), kinase activity (GO:0016301), kinase activator activity (GO:0019209)

GO Cellular Component (7): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), endosome membrane (GO:0010008), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	2
Toll Like Receptor 3 (TLR3) Cascade	2
TRIF (TICAM1)-mediated TLR4 signaling	2
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	2
MyD88 cascade initiated on plasma membrane	2
MAP kinase activation	2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
Fc epsilon receptor (FCERI) signaling	1
Interleukin-1 signaling	1
TNF signaling	1
C-type lectin receptors (CLRs)	1
Deubiquitination	1
Interleukin-1 family signaling	1
Innate Immune System	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
binding	3
cellular anatomical structure	3
heart development	2
intracellular signaling cassette	2
positive regulation of intracellular signal transduction	2
chordate embryonic development	1
animal organ morphogenesis	1
cardiac chamber development	1
anatomical structure development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
artery development	1
MAPK cascade	1
regulation of MAPK cascade	1
blood vessel development	1
regulation of cytoplasmic pattern recognition receptor signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
cGAS/STING signaling pathway	1
dephosphorylation	1
protein modification process	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
intracellular protein transport	1
cytoplasmic pattern recognition receptor signaling pathway	1
positive regulation of signal transduction	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
phosphoprotein phosphatase activity	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1

Protein interactions and networks

STRING

2931 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAB1	TAB2	Q9NYJ8	999
TAB1	MAP3K7	O43318	998
TAB1	TAB3	Q8N5C8	998
TAB1	TRAF6	Q9Y4K3	998
TAB1	XIAP	P98170	992
TAB1	ARRB2	P32121	979
TAB1	MAPK14	Q16539	973
TAB1	CHUK	O15111	930
TAB1	IKBKB	O14920	920
TAB1	IRAK1	P51617	916
TAB1	TGFBR1	P36897	882
TAB1	G3V2F7	G3V2F7	865
TAB1	UBE2N	P61088	841
TAB1	IRAK2	O43187	800
TAB1	IKBKG	Q9Y6K9	798

IntAct

251 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
XIAP	RIPK2	psi-mi:“MI:0914”(association)	0.950
TAB2	MAP3K7	psi-mi:“MI:0914”(association)	0.920
TAB2	TAB1	psi-mi:“MI:0915”(physical association)	0.910
MAP3K7	TAB1	psi-mi:“MI:0915”(physical association)	0.900
MAP3K7	TAB1	psi-mi:“MI:0914”(association)	0.900
TAB1	MAP3K7	psi-mi:“MI:0914”(association)	0.900
MAP3K7	TAB1	psi-mi:“MI:2364”(proximity)	0.900
TAB3	MAP3K7	psi-mi:“MI:0914”(association)	0.830
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
TAB1	XIAP	psi-mi:“MI:0915”(physical association)	0.750
XIAP	TAB1	psi-mi:“MI:0915”(physical association)	0.750
TAB1	HSPA8	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MAPK14	TAB1	psi-mi:“MI:2364”(proximity)	0.710
OGT	URI1	psi-mi:“MI:0559”(glycosylation reaction)	0.670
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
TRAF6	MAP3K7	psi-mi:“MI:0914”(association)	0.670
EGFR	TAB1	psi-mi:“MI:0915”(physical association)	0.650
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640

BioGRID (390): XIAP (Affinity Capture-Western), NAIP (Affinity Capture-Western), BIRC7 (Affinity Capture-Western), TAB1 (Affinity Capture-RNA), TAB1 (Affinity Capture-RNA), TAB1 (Affinity Capture-RNA), TAB1 (Reconstituted Complex), TAB2 (Reconstituted Complex), TAB1 (Two-hybrid), TAB1 (Reconstituted Complex), TAB1 (Biochemical Activity), TAB2 (Two-hybrid), TAB1 (Affinity Capture-MS), TAB1 (Affinity Capture-MS), TAB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A3A8W2, A4IF63, A6K136, D2GXS7, D3ZQG6, F7H9X2, O60733, O62829, O62830, O75688, O88483, P20650, P35813, P35814, P35816, P42694, P49443, P93006, P97570, P97819, Q05AL2, Q15750, Q28DF4, Q2PC20, Q3UV70, Q5F361, Q5R522, Q5RA52, Q5SMK6, Q69QZ0, Q69VD9, Q6ING9, Q6NYU2, Q6ZHC8, Q7XJ53, Q7XUC5, Q84JD5, Q8AYC9, Q8BXN7

Diamond homologs: O64583, Q15750, Q5SN75, Q65XK7, Q8CF89, Q9FIF5, Q9FXE4

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
SMAD6	down-regulates	TAB1	binding
SMAD7	down-regulates	TAB1	binding
TAB1	“up-regulates activity”	MAPK14	binding
MAPK14	“down-regulates activity”	TAB1	phosphorylation
TAB1	“up-regulates activity”	MAP3K7	binding
TAB1	down-regulates	ROR2	phosphorylation
TAB1	up-regulates	JNK	binding
TAB1	up-regulates	p38	binding
TRAF6	“up-regulates activity”	TAB1	binding
MAP3K7	“up-regulates activity”	TAB1	phosphorylation
DUSP14	“down-regulates activity”	TAB1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	42.0×	5e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	37.0×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	37.0×	1e-08
activated TAK1 mediates p38 MAPK activation	9	35.2×	2e-10
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	8	32.7×	3e-09
TNFR1-induced NF-kappa-B signaling pathway	12	31.7×	9e-13
Activation of BH3-only proteins	8	31.3×	4e-09
NOD1/2 Signaling Pathway	12	30.0×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	6	31.8×	6e-06
canonical NF-kappaB signal transduction	12	27.6×	2e-11
protein refolding	7	27.5×	2e-06
stress-activated MAPK cascade	6	26.5×	1e-05
tumor necrosis factor-mediated signaling pathway	8	16.6×	6e-06
toll-like receptor 4 signaling pathway	5	16.6×	1e-03
response to unfolded protein	8	15.1×	1e-05
protein targeting	6	13.8×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2389 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39399832:GAGT:G	donor_gain	1.0000
22:39399834:GT:G	donor_gain	1.0000
22:39415496:CCAG:C	acceptor_loss	1.0000
22:39415496:CCAGG:C	acceptor_gain	1.0000
22:39415497:CAGG:C	acceptor_gain	1.0000
22:39415498:A:AG	acceptor_gain	1.0000
22:39415498:A:AT	acceptor_loss	1.0000
22:39415498:AG:A	acceptor_gain	1.0000
22:39415498:AGGA:A	acceptor_gain	1.0000
22:39415499:G:GG	acceptor_gain	1.0000
22:39415499:GG:G	acceptor_gain	1.0000
22:39415499:GGA:G	acceptor_gain	1.0000
22:39415499:GGAG:G	acceptor_gain	1.0000
22:39415499:GGAGT:G	acceptor_gain	1.0000
22:39415651:CAG:C	donor_loss	1.0000
22:39415652:AGGTA:A	donor_loss	1.0000
22:39415654:G:GA	donor_loss	1.0000
22:39415655:T:G	donor_loss	1.0000
22:39416788:TAGG:T	acceptor_loss	1.0000
22:39416789:A:AG	acceptor_gain	1.0000
22:39416789:A:T	acceptor_loss	1.0000
22:39416790:G:GG	acceptor_gain	1.0000
22:39416790:GGCC:G	acceptor_gain	1.0000
22:39416875:GAG:G	donor_gain	1.0000
22:39417709:AG:A	acceptor_gain	1.0000
22:39417710:GG:G	acceptor_gain	1.0000
22:39417710:GGGA:G	acceptor_gain	1.0000
22:39417845:TGTCG:T	donor_loss	1.0000
22:39417846:GTCG:G	donor_gain	1.0000
22:39417850:G:GA	donor_loss	1.0000

AlphaMissense

3298 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39415021:T:A	W17R	0.999
22:39415021:T:C	W17R	0.999
22:39415023:G:C	W17C	0.999
22:39415023:G:T	W17C	0.999
22:39415592:T:C	L88P	0.999
22:39417841:C:A	A181D	0.999
22:39418747:T:C	L189P	0.999
22:39419576:G:C	R241P	0.999
22:39419585:G:A	G244E	0.999
22:39426710:C:A	A310D	0.999
22:39426761:C:A	A327D	0.999
22:39426779:G:C	R333P	0.999
22:39426860:T:C	L360P	0.999
22:39430166:T:C	F487L	0.999
22:39430168:T:A	F487L	0.999
22:39430168:T:G	F487L	0.999
22:39415042:T:C	C24R	0.998
22:39415526:G:A	G66E	0.998
22:39415580:T:C	L84P	0.998
22:39416791:G:C	A109P	0.998
22:39417840:G:C	A181P	0.998
22:39417849:G:C	G184R	0.998
22:39418732:G:A	G184D	0.998
22:39418732:G:T	G184V	0.998
22:39418741:G:C	R187P	0.998
22:39421900:T:C	F284L	0.998
22:39421902:C:A	F284L	0.998
22:39421902:C:G	F284L	0.998
22:39421916:C:G	S289W	0.998
22:39426770:T:A	V330D	0.998

dbSNP variants (sampled 300 via entrez): RS1000049465 (22:39433917 C>T), RS1000105901 (22:39425909 G>A), RS1000162606 (22:39434053 A>G), RS1000322641 (22:39433737 C>A,G,T), RS1000337588 (22:39423216 C>G), RS1000370266 (22:39423626 AG>A), RS1000476899 (22:39428842 G>A,C,T), RS1000497907 (22:39435061 G>A,T), RS1000507958 (22:39399046 G>A), RS1000518410 (22:39408223 G>T), RS1000641940 (22:39398939 A>G), RS1000657857 (22:39434881 T>C), RS1000702280 (22:39424705 C>T), RS1000817236 (22:39424855 C>T), RS1000855172 (22:39418389 G>A)

Disease associations

OMIM: gene MIM:602615 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000879_47	Crohn’s disease	1.000000e-26
GCST001010_16	Primary biliary cholangitis	1.000000e-09
GCST001725_110	Inflammatory bowel disease	4.000000e-33
GCST001848_106	IgG glycosylation	2.000000e-06
GCST001848_127	IgG glycosylation	6.000000e-10
GCST001848_132	IgG glycosylation	2.000000e-15
GCST001848_216	IgG glycosylation	6.000000e-16
GCST001848_290	IgG glycosylation	5.000000e-10
GCST001848_311	IgG glycosylation	3.000000e-08
GCST001848_342	IgG glycosylation	2.000000e-10
GCST001848_399	IgG glycosylation	3.000000e-13
GCST001848_428	IgG glycosylation	3.000000e-09
GCST001848_444	IgG glycosylation	2.000000e-10
GCST001848_460	IgG glycosylation	1.000000e-10
GCST001848_477	IgG glycosylation	3.000000e-09
GCST001848_563	IgG glycosylation	1.000000e-24
GCST001848_592	IgG glycosylation	1.000000e-16
GCST001848_632	IgG glycosylation	9.000000e-24
GCST001848_74	IgG glycosylation	9.000000e-06
GCST001849_3	IgG glycosylation	3.000000e-08
GCST001849_5	IgG glycosylation	2.000000e-10
GCST001849_6	IgG glycosylation	9.000000e-06
GCST004924_5	IgG monogalactosylation phenotypes (multivariate analysis)	1.000000e-06
GCST004925_5	IgG N-glycosylation phenotypes (multivariate analysis)	3.000000e-19
GCST004926_5	IgG digalactosylation phenotypes (multivariate analysis)	3.000000e-13
GCST004927_4	IgG galactosylation phenotypes (multivariate analysis)	2.000000e-14
GCST004928_3	IgG bisecting N-acetyl glucosamine phenotypes (multivariate analysis)	4.000000e-10
GCST004929_4	IgG fucosylation phenotypes (multivariate analysis)	1.000000e-20
GCST004930_4	IgG sialylation phenotypes (multivariate analysis)	1.000000e-13
GCST004931_3	IgG disialylation phenotypes (multivariate analysis)	4.000000e-14

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0005193	serum IgG glycosylation measurement
EFO:0008423	IgG monogalactosylation measurement
EFO:0008424	IgG digalactosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008426	IgG bisecting N-acetyl glucosamine measurement
EFO:0008427	IgG fucosylation measurement
EFO:0008428	IgG sialylation measurement
EFO:0008429	IgG disialylation measurement
EFO:0004337	intelligence
EFO:0004630	factor VIII measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3038499 (PROTEIN COMPLEX), CHEMBL3885612 (CHIMERIC PROTEIN), CHEMBL5605 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,219 (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
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1232461	MOLIBRESIB	2	1,538

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

Binding affinities (BindingDB)

47 measured of 50 human assays (50 total across all organisms); most potent 47 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(E)-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	3.1 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-(4-butan-2-yloxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enamide	IC50	4.3 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-(4-propan-2-yloxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enamide	IC50	4.4 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-(2,2-dimethylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	5.2 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-ynamide	IC50	7 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(4S,6E,9S,10S,12E)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	IC50	11 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(E)-3-[4-[(2-methylpropan-2-yl)oxy]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	13 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-(4,4-difluorocyclohexyl)oxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	16 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-(4-propoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enamide	IC50	19 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-(2,2,2-trifluoroethoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	33 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
CHEBI:83275	IC50	33 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(E)-N-methyl-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	41 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-[(3-fluorophenyl)methoxy]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	51 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-(2-hydroxy-2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	75 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(4S,6Z,9S,10S,12E)-15,15-difluoro-9,10-dihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,16-tetraene-2,8,18-trione	IC50	77 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(E)-N,N-dimethyl-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	97 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-4-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]but-3-en-2-one	IC50	100 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(Z)-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enenitrile	IC50	170 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-(4-phenoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enamide	IC50	170 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-N-cyclopropyl-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	180 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-1-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pent-1-en-3-one	IC50	200 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
methyl (E)-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enoate	IC50	200 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enenitrile	IC50	210 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
2-chloro-1-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]ethanone	IC50	280 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-(4-phenylmethoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enenitrile	IC50	330 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enoic acid	IC50	340 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-N-ethyl-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	340 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
methyl (E)-3-(4-phenylmethoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enoate	IC50	350 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(Z)-2-chloro-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	360 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(4S,6Z,9S,10S,12E)-15-bromo-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	IC50	360 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(E)-N-(cyclopropylmethyl)-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	380 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(2E,5S,9S,11Z,14S)-18-hydroxy-20-methoxy-7,7,14-trimethyl-6,8,15-trioxatricyclo[15.4.0.05,9]henicosa-1(17),2,11,18,20-pentaene-10,16-dione	IC50	380 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(E)-4-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]but-2-enamide	IC50	420 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
methyl (E)-2-methyl-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enoate	IC50	430 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	IC50	560 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-3-(4-phenylmethoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)prop-2-enamide	IC50	730 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
2-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enenitrile	IC50	750 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(Z)-2-fluoro-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	860 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(2S,4S,6S,7S,9Z,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraene-8,14-dione	IC50	990 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
CHEBI:67558	IC50	1300 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(E)-N-[(2S)-2-hydroxypropyl]-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	1600 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
1-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]ethanone	IC50	1700 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(E)-N-[(2R)-2-hydroxypropyl]-3-[4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]prop-2-enamide	IC50	2500 nM	US-9505765: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment
(4S,6Z,9S,10S,12E)-17-bromo-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(18),6,12,14,16-pentaene-2,8-dione	IC50	2600 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(4S,9S,10S,12E)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),12,15,17-tetraene-2,8-dione	IC50	2600 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
(4S,6Z,9S,10S,12E)-15,17-dibromo-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	IC50	8900 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones
ZEAENOL	IC50	10000 nM	US-10434085: Non-aromatic difluoro analogues of resorcylic acid lactones

ChEMBL bioactivities

215 potent at pChembl≥5 of 228 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL4796239
8.51	IC50	3.1	nM	CHEMBL3953067
8.40	IC50	4	nM	CHEMBL2407759
8.37	IC50	4.3	nM	CHEMBL3916326
8.36	IC50	4.4	nM	CHEMBL3924740
8.30	IC50	5	nM	CHEMBL4752978
8.28	IC50	5.2	nM	CHEMBL3919781
8.15	IC50	7	nM	CHEMBL3917140
8.10	IC50	8	nM	CHEMBL3823303
8.10	IC50	8	nM	CHEMBL1077979
8.05	IC50	9	nM	CHEMBL2408610
8.05	IC50	9	nM	CHEMBL1077979
8.05	IC50	8.9	nM	CHEMBL1761718
8.00	IC50	10	nM	CHEMBL2408611
7.89	IC50	13	nM	CHEMBL2407758
7.89	IC50	13	nM	CHEMBL3898170
7.85	IC50	14	nM	CHEMBL2408616
7.80	IC50	16	nM	CHEMBL3912681
7.77	IC50	17	nM	CHEMBL2408615
7.75	IC50	18	nM	CHEMBL2407761
7.72	IC50	19	nM	CHEMBL3905384
7.68	IC50	21	nM	CHEMBL1761588
7.64	IC50	23	nM	CHEMBL2407757
7.55	IC50	28	nM	CHEMBL2408611
7.52	IC50	30	nM	CHEMBL2407760
7.52	IC50	30	nM	CHEMBL3823738
7.52	IC50	30	nM	HYPOTHEMYCIN
7.51	IC50	31	nM	CHEMBL2408614
7.48	IC50	33	nM	CHEMBL3901893
7.46	IC50	35	nM	STAUROSPORINE
7.43	IC50	37	nM	CHEMBL4586372
7.41	IC50	39	nM	STAUROSPORINE
7.39	IC50	41	nM	CHEMBL3918925
7.39	IC50	41	nM	CHEMBL4535889
7.38	IC50	42	nM	CHEMBL1761586
7.34	IC50	46	nM	CHEMBL1761585
7.29	IC50	51	nM	CHEMBL3969384
7.27	IC50	54	nM	CHEMBL4443805
7.21	IC50	61	nM	CHEMBL2407795
7.12	IC50	75	nM	CHEMBL3895287
7.05	IC50	89	nM	CHEMBL2407792
7.01	IC50	97	nM	CHEMBL3919897
7.00	IC50	100	nM	CHEMBL3963009
7.00	IC50	99	nM	CHEMBL1761587
6.96	IC50	110	nM	CHEMBL2408613
6.89	IC50	130	nM	CHEMBL2407966
6.82	IC50	150	nM	CHEMBL2408617
6.80	IC50	160	nM	CHEMBL2408612
6.77	IC50	170	nM	CHEMBL3894718
6.77	IC50	170	nM	CHEMBL3902720

PubChem BioAssay actives

143 with measured affinity, of 298 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-[5-[[2-(difluoromethoxy)phenyl]methyl-[(2R)-1-(methylamino)-1-oxopropan-2-yl]carbamoyl]-1H-imidazole-2-carbonyl]-1,3-dihydroisoindole-5-carboxamide	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.0020	uM
1-[4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0040	uM
2-[5-[[2-(difluoromethoxy)phenyl]methyl-[2-(methylamino)-2-oxoethyl]carbamoyl]-1H-imidazole-2-carbonyl]-1,3-dihydroisoindole-5-carboxamide	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.0050	uM
1-[2-[3-ethyl-5-[(5-fluoro-4-imidazo[1,2-b]pyridazin-3-ylpyrimidin-2-yl)amino]phenoxy]ethyl]piperidin-4-ol	1613077: Inhibition of N-terminal His-tagged human TAK1 (1 to 303 amino acids)/human TAB1 (437 to 504 amino acids) expressed in baculovirus expression system using fluorescence-labeled substrate by off-chip mobility shift assay	ic50	0.0080	uM
(4S,6Z,9S,10S,12E)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.0080	uM
(2Z)-2-[(Z)-(5-bromo-2-oxo-1H-indol-3-ylidene)hydrazinylidene]-3-(4-hydroxyphenyl)-1,3-thiazolidin-4-one	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.0089	uM
4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]cyclohexan-1-ol	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.0090	uM
4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-chlorofuro[2,3-c]pyridin-4-yl]pyrazol-1-yl]cyclohexan-1-ol	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.0100	uM
1-[4-[4-[7-amino-2-(1,3-benzothiazol-7-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0130	uM
4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-(difluoromethyl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]cyclohexan-1-ol	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.0140	uM
4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-(fluoromethyl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]cyclohexan-1-ol	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.0170	uM
1-[4-[4-[7-amino-2-(1-methylpyrrolo[2,3-c]pyridin-3-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0180	uM
(2Z)-2-[(Z)-(5-chloro-2-oxo-1H-indol-3-ylidene)hydrazinylidene]-3-(4-hydroxyphenyl)-1,3-thiazolidin-4-one	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.0210	uM
1-[4-[4-[7-amino-2-(1,2-benzothiazol-7-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0230	uM
N-[3-(4-methylpiperazine-1-carbonyl)-2-propan-2-yloxyphenyl]-4-oxo-3H-thieno[3,2-d]pyrimidine-7-carboxamide	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.0300	uM
1-[4-[4-(7-amino-2-thieno[2,3-c]pyridin-3-ylfuro[2,3-c]pyridin-4-yl)pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0300	uM
(2R,4R,6S,7S,9Z,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraene-8,14-dione	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.0300	uM
4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-(1,3-thiazol-5-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]cyclohexan-1-ol	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.0310	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	350297: Inhibition of TAB1	ic50	0.0350	uM
1-(3-tert-butyl-1-phenylpyrazol-5-yl)-3-[4-[8-(cyclopropylamino)imidazo[1,2-a]pyrazin-5-yl]-3-methylphenyl]urea	1613077: Inhibition of N-terminal His-tagged human TAK1 (1 to 303 amino acids)/human TAB1 (437 to 504 amino acids) expressed in baculovirus expression system using fluorescence-labeled substrate by off-chip mobility shift assay	ic50	0.0370	uM
1-[3-tert-butyl-1-(3-cyanophenyl)pyrazol-5-yl]-3-[4-[8-(cyclopropylamino)imidazo[1,2-a]pyrazin-5-yl]-3-methylphenyl]urea	1613077: Inhibition of N-terminal His-tagged human TAK1 (1 to 303 amino acids)/human TAB1 (437 to 504 amino acids) expressed in baculovirus expression system using fluorescence-labeled substrate by off-chip mobility shift assay	ic50	0.0410	uM
(2Z)-3-(4-hydroxyphenyl)-2-[(Z)-(5-methyl-2-oxo-1H-indol-3-ylidene)hydrazinylidene]-1,3-thiazolidin-4-one	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.0420	uM
(2Z)-3-(4-hydroxyphenyl)-2-[(Z)-(2-oxo-1H-indol-3-ylidene)hydrazinylidene]-1,3-thiazolidin-4-one	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.0460	uM
1-[4-[[5-[6-(methylamino)pyrazin-2-yl]-2-(4-morpholin-4-ylanilino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]piperidin-1-yl]prop-2-en-1-one	1551693: Inhibition of tracer 222 binding to recombinant full-length human His-tagged MAP3K7/MAP3K7IP1 (437 to 504 residues) expressed in baculovirus expression system by Lanthascreen assay	ic50	0.0540	uM
1-[4-[4-[7-amino-2-(3-hydroxyphenyl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0610	uM
1-[4-[4-[7-amino-2-(3-nitrophenyl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.0890	uM
(2Z)-2-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)hydrazinylidene]-3-(4-hydroxyphenyl)-1,3-thiazolidin-4-one	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.0990	uM
4-[4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-pyridin-3-ylfuro[2,3-c]pyridin-4-yl]pyrazol-1-yl]cyclohexan-1-ol	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.1100	uM
1-[4-[4-[7-amino-2-(1H-pyrazol-4-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.1300	uM
4-(1-methylpyrazol-4-yl)-2-thieno[2,3-c]pyridin-3-ylfuro[2,3-c]pyridin-7-amine	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.1500	uM
7-amino-2-(1,2,3-benzothiadiazol-7-yl)-4-[1-(4-hydroxycyclohexyl)pyrazol-4-yl]furo[2,3-c]pyridine-3-carbonitrile	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.1600	uM
methyl N-[4-[6-[(2S)-2-amino-2,4-dimethylpentoxy]-5-methyl-3-pyridinyl]-2-pyridinyl]carbamate	1904687: Inhibition of TAK/TAB (unknown origin)	ic50	0.1800	uM
4-(2-methyl-1,3-thiazol-5-yl)-2-thieno[2,3-c]pyridin-3-ylfuro[2,3-c]pyridin-7-amine	762866: Inhibition of TAK1-TAB1 (unknown origin) by alphascreen assay in presence of ATP	ic50	0.2300	uM
3-[4-[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]-7-aminofuro[2,3-c]pyridin-2-yl]benzonitrile	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.2500	uM
2-[2-[4-[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]-7-aminofuro[2,3-c]pyridin-2-yl]phenyl]acetonitrile	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.2500	uM
1-[4-[4-[7-amino-2-(4-hydroxyphenyl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.2700	uM
N-[[2-(difluoromethoxy)phenyl]methyl]-2-(1,3-dihydroisoindole-2-carbonyl)-N-[2-(methylamino)-2-oxoethyl]-1H-imidazole-5-carboxamide	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.3000	uM
N-[[2-(difluoromethoxy)phenyl]methyl]-N-[(2R)-1-(methylamino)-1-oxopropan-2-yl]-2-(pyrrolidine-1-carbonyl)-1H-imidazole-5-carboxamide	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.3000	uM
1-[4-[4-[7-amino-2-(1-benzothiophen-3-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.3400	uM
(Z)-4-[[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl]oxy]-4-oxobut-2-enoic acid	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.3800	uM
[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl] acetate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.4300	uM
1-[4-[4-[7-amino-2-(2-methylsulfanylphenyl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.4300	uM
[(2R,4R,6S,7S,9Z,12S)-6,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-7-yl] acetate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.4500	uM
1-[4-[4-[7-amino-2-(cyclohexen-1-yl)furo[2,3-c]pyridin-4-yl]pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.4600	uM
1-[4-[4-(7-amino-2-thiophen-3-ylfuro[2,3-c]pyridin-4-yl)pyrazol-1-yl]piperidin-1-yl]ethanone	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.4800	uM
N-[[2-(difluoromethoxy)phenyl]methyl]-N-[1-(methylamino)-1-oxopropan-2-yl]-2-(pyrrolidine-1-carbonyl)-1H-imidazole-5-carboxamide	1709608: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay	ic50	0.5000	uM
[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl] ethyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.5000	uM
3-[4-[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]-7-aminofuro[2,3-c]pyridin-2-yl]benzamide	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.5300	uM
(3Z)-3-[2-(3,4-dihydroxyphenyl)-2-oxoethylidene]-1H-indol-2-one	589426: Competitive inhibition of recombinant TAK1-TAB1 assessed as [33P]gamma-ATP incorporation into substrate histone H1 peptide by filter plate assay	ic50	0.5600	uM
2-[4-[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]-7-aminofuro[2,3-c]pyridin-2-yl]benzonitrile	762666: Inhibition of truncated TAK1-TAB1(unknown origin) using MKK7 as substrate by ALPHAScreen assay in presence of ATP	ic50	0.5600	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Benzo(a)pyrene	decreases methylation, affects methylation	2
2-anisidine	decreases expression	1
beta-lapachone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
obeticholic acid	decreases expression	1
jinfukang	increases expression	1
Aripiprazole	affects cotreatment, decreases expression	1
Caffeine	decreases phosphorylation	1
Chelating Agents	affects binding, decreases expression	1
Copper	decreases expression, affects binding	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects binding	1
Ozone	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Simvastatin	affects cotreatment, decreases activity	1

ChEMBL screening assays

58 unique, capped per target: 58 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1105931	Binding	Inhibition of TAK1/TAB1 at 5 uM	Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 3 embryonic stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6W6	SEES3-1V human TAB1, clone1	Embryonic stem cell	Male
CVCL_A6W7	SEES3-1V human TAB1, clone2	Embryonic stem cell	Male
CVCL_A6W8	SEES3-1V human TAB1, clone3	Embryonic stem cell	Male
CVCL_B3IW	Abcam HEK293T TAB1 KO	Transformed cell line	Female
CVCL_D8BX	Ubigene A-549 TAB1 KO	Cancer cell line	Male
CVCL_D8WR	Ubigene HCT 116 TAB1 KO	Cancer cell line	Male
CVCL_D9TS	Ubigene HEK293 TAB1 KO	Transformed cell line	Female
CVCL_E0QE	Ubigene HeLa TAB1 KO	Cancer cell line	Female
CVCL_TR41	HAP1 TAB1 (-) 1	Cancer cell line	Male
CVCL_TR42	HAP1 TAB1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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