IKBKE

Summary

IKBKE (inhibitor of nuclear factor kappa B kinase subunit epsilon, HGNC:14552) is a protein-coding gene on chromosome 1q32.1, encoding Inhibitor of nuclear factor kappa-B kinase subunit epsilon (Q14164). Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling.

IKBKE is a noncanonical I-kappa-B (see MIM 164008) kinase (IKK) that is essential for regulating antiviral signaling pathways. IKBKE has also been identified as a breast cancer (MIM 114480) oncogene and is amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines (Hutti et al., 2009 [PubMed 19481526]).

Source: NCBI Gene 9641 — RefSeq curated summary.

At a glance

• Gene–disease (curated): encephalitis, acute, infection-induced, susceptibility to (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 117 total
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14552
Approved symbol	IKBKE
Name	inhibitor of nuclear factor kappa B kinase subunit epsilon
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	IKKE, IKK-i, KIAA0151
Ensembl gene	ENSG00000263528
Ensembl biotype	protein_coding
OMIM	605048
Entrez	9641

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 retained_intron

ENST00000578328, ENST00000579827, ENST00000581977, ENST00000584998, ENST00000605726, ENST00000605818, ENST00000900001, ENST00000900002, ENST00000900004, ENST00000900006, ENST00000900007, ENST00000912133, ENST00000912134, ENST00000944419, ENST00000944420

RefSeq mRNA: 3 — MANE Select: NM_014002 NM_001193321, NM_001193322, NM_014002

CCDS: CCDS30996, CCDS53464, CCDS73019

Canonical transcript exons

ENST00000581977 — 22 exons

Exon	Start	End
ENSE00002687376	206470476	206470698
ENSE00002689552	206471156	206471245
ENSE00002704377	206477749	206477859
ENSE00003459310	206493920	206493991
ENSE00003471158	206493266	206493378
ENSE00003483164	206493023	206493119
ENSE00003491981	206491648	206491749
ENSE00003495897	206480447	206480533
ENSE00003532649	206487914	206487990
ENSE00003552185	206479870	206479934
ENSE00003558636	206474865	206474994
ENSE00003562419	206478943	206479133
ENSE00003582354	206496112	206496889
ENSE00003594756	206480022	206480113
ENSE00003604685	206474331	206474471
ENSE00003616972	206476181	206476362
ENSE00003627537	206490819	206490858
ENSE00003631223	206485194	206485306
ENSE00003659428	206476678	206476838
ENSE00003670649	206473196	206473314
ENSE00003673974	206484997	206485072
ENSE00003693149	206478160	206478339

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5422 / max 115.1080, expressed in 1697 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8084	10.5422	1697

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	97.52	gold quality
granulocyte	CL:0000094	90.96	gold quality
monocyte	CL:0000576	86.96	gold quality
leukocyte	CL:0000738	86.77	gold quality
mononuclear cell	CL:0000842	86.61	gold quality
blood	UBERON:0000178	83.56	gold quality
lymph node	UBERON:0000029	83.35	gold quality
bone marrow cell	CL:0002092	83.03	gold quality
vermiform appendix	UBERON:0001154	82.79	gold quality
esophagus mucosa	UBERON:0002469	82.09	gold quality
tonsil	UBERON:0002372	81.77	gold quality
mucosa of transverse colon	UBERON:0004991	81.55	gold quality
spleen	UBERON:0002106	81.36	gold quality
lower esophagus mucosa	UBERON:0035834	80.31	gold quality
caecum	UBERON:0001153	79.43	gold quality
stromal cell of endometrium	CL:0002255	78.88	gold quality
palpebral conjunctiva	UBERON:0001812	78.08	gold quality
rectum	UBERON:0001052	77.76	gold quality
skin of abdomen	UBERON:0001416	77.53	gold quality
skin of leg	UBERON:0001511	76.31	gold quality
minor salivary gland	UBERON:0001830	75.90	gold quality
pancreatic ductal cell	CL:0002079	75.59	silver quality
small intestine	UBERON:0002108	75.30	gold quality
zone of skin	UBERON:0000014	75.00	gold quality
mouth mucosa	UBERON:0003729	74.99	gold quality
gall bladder	UBERON:0002110	74.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.72	gold quality
right adrenal gland cortex	UBERON:0035827	74.53	gold quality
ileal mucosa	UBERON:0000331	74.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, DLX4, FOXA3, IRF3, IRF6, NFKB, NFKBIA, RELA, STAT3, TRIM6, ZNF382

miRNA regulators (miRDB)

45 targeting IKBKE, 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-4533	100.00	69.48	2758
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-6760-5P	98.87	66.73	1515

Literature-anchored findings (GeneRIF, showing 40)

• The IkappaB kinase (IKK) complex, composed of two catalytic subunits (IKKalpha and IKKbeta) and a regulatory subunit (IKKgamma), is the key enzyme in activation of nuclear factor kappaB. IKK was recombinantly expressed in a model organism that lacks IKK. (PMID:11470787)
• IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. (IKK-i kinase) (PMID:11839743)
• Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with specific kinases (PMID:12133833)
• Expression of IkappaB kinase frees the oncogenic functions of Ras and results in invasive carcinoma resembling squamous cell carcinoma. (PMID:12676577)
• IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response. (PMID:12692549)
• IKKi/IKKepsilon plays a key role in integrating signals induced by pro-inflammatory stimuli. (PMID:12736252)
• data suggest that intracellular RNP formation contributes to the early recognition of vesicular stomatitis virus infection, activates the catalytic activity of TBK1, and induces transcriptional upregulation of IKKepsilon in epithelial cells (PMID:15367631)
• IL-1-inducible phosphorylation of p65 NFkB is mediated by multiple protein kinases including IKKalpha, IKKbeta, IKKepsilon, TBK1, and an unknown kinase and couples p65 to TAFII31-mediated IL-8 transcription (PMID:15489227)
• analysis of mechanism for selective inhibition of TNF but not IL-1beta-induced IKK activation (PMID:15550384)
• The partial restoration of the capacity of the host cell to transcribe IFN-beta indicates that IKKepsilon expression is able to bypass the HCV-mediated inhibition and restore the innate antiviral response. (PMID:15767399)
• IKK epsilon protein is expressed in rheumatoid arthritis and osteoarthritis synovium, where the protein is found primarily in the synovial intimal lining. (PMID:15879144)
• Targeting IkappaB kinases may represent an attractive therapeutic approach against these malignancies regardless of the mutational status of IkappaBalpha. (PMID:16299251)
• interferon-A genes differentially affects virus-induced expression and responsiveness to TBK1 and IKKepsilon (PMID:16380379)
• HCV virus-induced IKKepsilon kinase, but not TBK1, colocalized strongly with MAVS at the mitochondrial membrane, and the localization of both molecules was disrupted by HC NS3-4A expression (PMID:16731946)
• IKK-i/IKKepsilon has a role in controlling proliferation of certain cancer cells through regulation of constitutive NF-kappaB activity (PMID:16840782)
• TBK1 and IKK epsilon directly phosphorylate the C-terminal domain of cRel in vitro and in vivo and regulate nuclear accumulation of cRel. (PMID:16888014)
• Novel interactions reveal a hitherto unknown function of IKKepsilon in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65 are reported. (PMID:17003035)
• TANK may be a critical adaptor that regulates the assembly of the TANK-binding kinase 1-inducible IkappaB kinase complex with upstream signaling molecules in multiple antiviral pathways (PMID:17327220)
• Antiviral gene expression in RA, especially due to TLR ligands and TNFalpha, is dependent on IKKepsilon and IRF-3, and this pathway plays a key role in the production of type I IFNs and chemokines such as RANTES. (PMID:17328045)
• IKBKE is a breast cancer oncogene (PMID:17574021)
• distinct scaffold proteins assemble IKK, and potentially TBK1 and IKK-epsilon subcomplexes, in a stimulus-specific manner, which might be a mechanism to achieve specificity [review] (PMID:18353649)
• These data suggest that VP35 exerts its interferon-antagonist function, at least in part, by blocking necessary interactions between the kinases IKKepsilon and TBK-1 and their normal interaction partners, including their substrates, IRF-3 and IRF-7. (PMID:19153231)
• recruitment of IKKepsilon to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-kappaB activation and expression of inflammatory and antiviral genes (PMID:19380491)
• Results suggest that IKKepsilon and CYLD function as an oncogene-tumor suppressor network that participates in tumorigenesis. (PMID:19481526)
• deregulation of IKKepsilon could play a pivotal role in human ovarian cancer progression and cisplatin resistance (PMID:19497997)
• up-regulation of IKBKE may represent an important molecular hallmark that is biologically and clinically relevant to the development and progression, as well as the chemo- and radio-resistance, of the disease. (PMID:21171089)
• Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (PMID:21179067)
• miR-K12-11 can contribute to maintenance of Kaposi’s sarcoma-associated herpesvirus latency by targeting IKKepsilon. (PMID:21221132)
• This study strongly suggests the role of IKKepsilon as a prostate cancer oncogene that may be involved in the emergence of a castrate-resistent state. (PMID:21271611)
• IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. (PMID:21464307)
• These data indicate that deregulation of IKKepsilon is a common event in pancreatic ductal adenocarcinoma and might have an important role in the pathogenesis of this deadly disease. (PMID:21685032)
• IKKepsilon is overexpressed in many breast cancers and phosphorylates numerous targets involved in new oncogenic signaling pathways. It is involved in tamoxifen resistance. Review. (PMID:21718646)
• Inhibitor of kappaB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 proteins define novel innate immune effector pathway against West Nile virus infection. (PMID:22065572)
• IKKepsilon regulated Sendai virus-induced apoptosis via the phosphorylation-dependent turnover of XIAP. (PMID:22072751)
• IKBKE and gene expression patterns for other members of the NF-kappaB pathway were not associated with survival, suggesting that IKBKE gene expression may be an independent marker of variation in overall survival (PMID:22266464)
• identify FOXO3 as a new IKK-epsilon-controlled check-point of IRF activation and regulation of IFN-beta expression, providing new insight into the role of FOXO3 in immune response control. (PMID:22531926)
• NP-IKKepsilon interaction likely plays a crucial role in arenavirus-host interaction. (PMID:22532683)
• deregulation of IKKepsilon plays a pivotal role in the uncontrolled proliferation and malignant invasion of glioma cells (PMID:22552702)
• phosphorylation of IRF7 on Ser477 and Ser479 by IKKepsilon or TBK1 is inhibited by KSHV ORF45 (PMID:22787218)
• these data provide evidence that IKK-epsilon is a key coordinator of invasion and metastasis programs in ovarian cancer (PMID:22942254)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ikbke	ENSDARG00000070606
mus_musculus	Ikbke	ENSMUSG00000042349
rattus_norvegicus	Ikbke	ENSRNOG00000025100
drosophila_melanogaster	IKKepsilon	FBGN0086657

Paralogs (3): IKBKB (ENSG00000104365), TBK1 (ENSG00000183735), CHUK (ENSG00000213341)

Protein

Protein identifiers

Inhibitor of nuclear factor kappa-B kinase subunit epsilon — Q14164 (reviewed: Q14164)

Alternative names: Inducible I kappa-B kinase

All UniProt accessions (4): A0A075B7B4, A0A075B7C7, A0A075B7D5, Q14164

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at ‘Ser-708’. Phosphorylation of STAT1 at ‘Ser-708’ also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.

Subunit / interactions. Homodimer. Interacts with MAVS/IPS1. Interacts (via protein kinase domain) with TTLL12 (via N-terminus); the interaction prevents MAVS binding to IKBKE. Interacts with the adapter proteins AZI2/NAP1, TANK and TBKBP1/SINTBAD. Interacts with SIKE1. Interacts with TICAM1/TRIF, IRF3 and RIGI; interactions are disrupted by the interaction between IKBKE and SIKE1. Interacts with TOPORS; induced by DNA damage. Interacts with CYLD. Interacts (when polyubiquitinated) with IKBKB, IKBKG and MYD88. Interacts with IFIH1. Interacts with DDX3X; the interaction may be induced upon virus infection. Interacts with TRIM6 (via SPRY box). Interacts with unanchored K48-linked polyubiquitin chains; this leads to IKBKE activation. Interacts with TBK1. Interacts with FKBP5. (Microbial infection) Interacts (via Protein kinase domain) with arenavirus protein N; the interaction inhibits IKBKE kinase function. (Microbial infection) Interacts with Ebola virus protein VP35; the interaction leads to inhibition of cellular antiviral response by blocking necessary interactions between the IKBKE and MAVS/IPS as well as its substrates IRF3 and IRF7. (Microbial infection) Interacts with Severe fever with thrombocytopenia virus (SFTSV) NSs; this interaction this interaction sequesters IKBKE in NSs-induced cytoplasmic inclusion bodies thereby inhibiting the IFN responses. (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein HBZ. (Microbial infection) Interacts with Epstein-Barr virus (EBV) protein NEC2/BFRF1; this interaction inhibits IKBKE kinase activity and IRF3 nuclear translocation.

Subcellular location. Cytoplasm. Nucleus. PML body.

Tissue specificity. Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon.

Post-translational modifications. Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-501 upon IFN activation. Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1. ‘Lys-63’-linked polyubiquitinated at Lys-30 and Lys-401 by TRAF2:BIRC2 and TRAF2:BIRC3 complexes. Ubiquitination is induced by LPS, TNFA and interleukin-1 and required for full kinase activity and KF-kappa-B pathway activation.

Induction. Induced by lipopolysaccharide (LPS) and TNFA.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14164-1	1	yes
Q14164-2	2

RefSeq proteins (3): NP_001180250, NP_001180251, NP_054721* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR041087	TBK1_ULD	Domain
IPR041309	TBK1_CC1	Domain
IPR051180	IKK	Family

Pfam: PF00069, PF18394, PF18396

Enzyme classification (BRENDA):

• EC 2.7.11.10 — IkappaB kinase (BRENDA: 7 organisms, 122 substrates, 335 inhibitors, 1 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• L-seryl-[I-kappa-B protein] + ATP = O-phospho-L-seryl-[I-kappa-B protein] + ADP + H(+) (RHEA:19073)

UniProt features (34 total): mutagenesis site 11, sequence variant 8, cross-link 3, modified residue 3, region of interest 2, binding site 2, chain 1, domain 1, splice variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14164-F1	88.81	0.71

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): 135 (proton acceptor)

Ligand- & substrate-binding residues (2): 15–23; 38

Post-translational modifications (6): 30, 231, 401, 172, 501, 664

Mutagenesis-validated functional residues (11):

Position	Phenotype
30	loss of ubiquitination and decreased kinase activity. no effect on homodimerization.
30	loss of ubiquitination and decreased kinase activity. decreases interaction with ikbkb, ikbkg and myd88. no effect on ho
38	loss of kinase activity and loss of nuclear import.
168	slight decrease of kinase activity.
172	loss of autophosphorylation and of kinase activity.
172	decrease in kinase activity.
231	loss of sumoylation and loss of targeting to nuclear bodies.
401	loss of ubiquitination and decreased kinase activity. no effect on homodimerization.
401	loss of ubiquitination and decreased kinase activity. decreases interaction with ikbkb, ikbkg and myd88. no effect on ho
416	no effect on ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-4755510	SUMOylation of immune response proteins
R-HSA-5357786	TNFR1-induced proapoptotic signaling
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-9013973	TICAM1-dependent activation of IRF3/IRF7
R-HSA-918233	TRAF3-dependent IRF activation pathway
R-HSA-933541	TRAF6 mediated IRF7 activation
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-936964	Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9824878	Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7
R-HSA-9828211	Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses

MSigDB gene sets: 391 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, GOBP_REGULATION_OF_LIPID_STORAGE, MORF_FLT1, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MSH3, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, MORF_BRCA1, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_RESPONSE_TO_TYPE_I_INTERFERON

GO Biological Process (21): activation of innate immune response (GO:0002218), immune response (GO:0006955), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), gene expression (GO:0010467), positive regulation of lipid storage (GO:0010884), positive regulation of type I interferon production (GO:0032481), response to interferon-beta (GO:0035456), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of protein-containing complex assembly (GO:0043254), mRNA stabilization (GO:0048255), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), interleukin-17-mediated signaling pathway (GO:0097400), cellular response to virus (GO:0098586), protein phosphorylation (GO:0006468), response to stress (GO:0006950), DNA damage response (GO:0006974), response to cytokine (GO:0034097), response to type I interferon (GO:0034340), intracellular signal transduction (GO:0035556)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), IkappaB kinase activity (GO:0008384), protein phosphatase binding (GO:0019903), ubiquitin protein ligase binding (GO:0031625), K48-linked polyubiquitin modification-dependent protein binding (GO:0036435), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), PML body (GO:0016605), mitochondrial membrane (GO:0031966), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
DDX58/IFIH1-mediated induction of interferon-alpha/beta	3
TNF signaling	2
SUMO E3 ligases SUMOylate target proteins	1
Toll Like Receptor 3 (TLR3) Cascade	1
TRIF (TICAM1)-mediated TLR4 signaling	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1
TICAM1-dependent activation of IRF3/IRF7	1
Response of endothelial cells to shear stress	1
Dengue Virus-Host Interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of innate immune response	2
response to stimulus	2
response to cytokine	2
response to virus	2
activation of immune response	1
immune system process	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
macromolecule biosynthetic process	1
regulation of lipid storage	1
lipid storage	1
positive regulation of cellular process	1
positive regulation of lipid localization	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
protein-containing complex assembly	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
defense response	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
positive regulation of cytokine-mediated signaling pathway	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-17	1
phosphorylation	1
protein modification process	1
cellular response to stress	1
response to peptide	1
innate immune response	1
protein kinase activity	1

Protein interactions and networks

STRING

2798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKBKE	TANK	Q92844	998
IKBKE	TRAF3	Q13114	998
IKBKE	MAVS	Q7Z434	998
IKBKE	IRF3	Q14653	995
IKBKE	IKBKG	Q9Y6K9	992
IKBKE	DDX3X	O00571	991
IKBKE	TBK1	Q9UHD2	983
IKBKE	AZI2	Q9H6S1	966
IKBKE	TRAF6	Q9Y4K3	965
IKBKE	TLR3	O15455	956
IKBKE	IFNB1	P01574	941
IKBKE	CHUK	O15111	939
IKBKE	RIGI	O95786	939
IKBKE	TBKBP1	A7MCY6	936
IKBKE	IFIH1	Q9BYX4	917

IntAct

458 interactions, top by confidence:

A	B	Type	Score
IKBKE	APPBP2	psi-mi:“MI:0915”(physical association)	0.500
IKBKE	TCP1	psi-mi:“MI:0914”(association)	0.350
IKBKE		psi-mi:“MI:0915”(physical association)	0.000
IKBKE	TMEM33	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	RAB14	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	RPL18A	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	GNB2	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	RAB7A	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	NTMT1	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	LRRC59	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	TRMT112	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	DLST	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	LRPPRC	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	FABP5	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	PPIB	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	RPS16	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	PFDN1	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	CKMT1A	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	AK2	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	EIF2S3	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	EEF1B2	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	EIF3D	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	MLEC	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	ECHS1	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	MIX23	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	RARS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (205): IKBKE (Affinity Capture-Western), UBC (Reconstituted Complex), APPBP2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT5 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT8 (Affinity Capture-MS), TANK (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TRAF2 (Affinity Capture-MS), IKBKE (Affinity Capture-Western), IKBKE (Reconstituted Complex), IFIT3 (Affinity Capture-Western)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

Diamond homologs: A7TIZ4, A8WRV1, O96017, P24719, P32742, P51957, Q14164, Q54RV3, Q54VU4, Q5RAJ5, Q6DFJ6, Q94A06, Q9NRP7, Q9R0T8, Q9WUN2, Q9Z1J2, Q9Z265, A1A5Q6, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8WYE4, A8X6H4, C0HKC8, C0HKC9, F4IRW0, F4JBP3, F4JY37, O08678, O08679, O24527, O43293, O54748, O54784, O88764

SIGNOR signaling

54 interactions.

A	Effect	B	Mechanism
IKBKE	up-regulates	RELA	phosphorylation
IKBKE	up-regulates	REL	phosphorylation
IKBKE	up-regulates	STAT1	phosphorylation
IKBKE	up-regulates	ESR1	phosphorylation
IKBKE	“down-regulates quantity by destabilization”	NFKBIA	phosphorylation
TBK1	“up-regulates activity”	IKBKE	binding
N-[3-[[5-iodo-4-[3-[[oxo(thiophen-2-yl)methyl]amino]propylamino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide	down-regulates	IKBKE	“chemical inhibition”
IKBKE	down-regulates	FOXO3	phosphorylation
IKBKE	“up-regulates activity”	NfKb-p65/p50	phosphorylation
IKBKE	up-regulates	REL/RELA	phosphorylation
IKBKE	down-regulates	FOXO	phosphorylation
MAVS	“up-regulates activity”	IKBKE	binding
IKBKE	“up-regulates activity”	TBK1	binding
ORF4b	“down-regulates activity”	IKBKE	binding
MOV10	“up-regulates activity”	IKBKE	binding
IKBKE	“up-regulates activity”	TRAF3IP2	phosphorylation
IKBKE	“down-regulates activity”	IRF1	phosphorylation
IKBKE	“down-regulates quantity by destabilization”	PBXIP1	phosphorylation
IKBKE	“up-regulates activity”	IKBKE	phosphorylation
IKBKE	“up-regulates activity”	NFATC1	phosphorylation
PPM1A	“down-regulates activity”	IKBKE	dephosphorylation
EGFR	“up-regulates activity”	IKBKE	phosphorylation
IKBKE	“down-regulates quantity by destabilization”	YAP1	phosphorylation
IKBKE	“down-regulates quantity by destabilization”	FAF1	phosphorylation

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
Antigen processing: Ub, ATP-independent proteasomal degradation	7	25.6×	6e-08
AUF1 (hnRNP D0) binds and destabilizes mRNA	16	25.5×	1e-16
Regulation of activated PAK-2p34 by proteasome mediated degradation	14	25.0×	2e-14
Regulation of ornithine decarboxylase (ODC)	14	24.4×	2e-14
Vpu mediated degradation of CD4	14	23.8×	2e-14
Autodegradation of the E3 ubiquitin ligase COP1	14	23.8×	2e-14
Ubiquitin-dependent degradation of Cyclin D	14	23.8×	2e-14
Hh mutants are degraded by ERAD	15	23.4×	6e-15

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	12	12.4×	2e-07
translational initiation	6	12.0×	2e-03
translation	14	8.0×	9e-07
protein folding	11	6.3×	3e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	19	5.5×	9e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3647 predictions. Top by Δscore:

Variant	Effect	Δscore
1:206471241:GTGGG:G	donor_gain	1.0000
1:206471243:GGG:G	donor_gain	1.0000
1:206471244:GGG:G	donor_gain	1.0000
1:206474309:ACT:A	acceptor_gain	1.0000
1:206474311:T:A	acceptor_gain	1.0000
1:206474323:A:AG	acceptor_gain	1.0000
1:206474323:AAT:A	acceptor_gain	1.0000
1:206474323:AATG:A	acceptor_gain	1.0000
1:206474324:A:AG	acceptor_gain	1.0000
1:206474325:T:A	acceptor_gain	1.0000
1:206474325:T:G	acceptor_gain	1.0000
1:206474326:G:A	acceptor_gain	1.0000
1:206474329:A:AG	acceptor_gain	1.0000
1:206474329:AGAA:A	acceptor_loss	1.0000
1:206474330:G:GT	acceptor_gain	1.0000
1:206474330:GA:G	acceptor_gain	1.0000
1:206474330:GAA:G	acceptor_gain	1.0000
1:206474330:GAAA:G	acceptor_gain	1.0000
1:206474330:GAAAT:G	acceptor_gain	1.0000
1:206474468:GACG:G	donor_gain	1.0000
1:206474472:G:GG	donor_gain	1.0000
1:206474472:GTAG:G	donor_loss	1.0000
1:206474473:T:G	donor_loss	1.0000
1:206474861:ATAG:A	acceptor_gain	1.0000
1:206474862:T:G	acceptor_gain	1.0000
1:206474862:TAG:T	acceptor_loss	1.0000
1:206474863:A:AC	acceptor_loss	1.0000
1:206474863:A:AG	acceptor_gain	1.0000
1:206474863:AG:A	acceptor_gain	1.0000
1:206474863:AGG:A	acceptor_gain	1.0000

AlphaMissense

4683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:206473252:T:A	W9R	0.999
1:206473252:T:C	W9R	0.999
1:206474357:G:C	K38N	0.999
1:206474357:G:T	K38N	0.999
1:206476223:G:C	R134P	0.999
1:206476226:A:C	D135A	0.999
1:206476226:A:T	D135V	0.999
1:206476242:C:A	N140K	0.999
1:206476242:C:G	N140K	0.999
1:206476291:G:C	D157H	0.999
1:206476292:A:C	D157A	0.999
1:206476292:A:G	D157G	0.999
1:206476292:A:T	D157V	0.999
1:206476293:C:A	D157E	0.999
1:206476293:C:G	D157E	0.999
1:206476357:T:C	Y179H	0.999
1:206476750:T:A	W205R	0.999
1:206476750:T:C	W205R	0.999
1:206476753:A:C	S206R	0.999
1:206476755:C:A	S206R	0.999
1:206476755:C:G	S206R	0.999
1:206473288:G:C	A21P	0.998
1:206473289:C:A	A21D	0.998
1:206474350:C:A	A36D	0.998
1:206474355:A:C	K38Q	0.998
1:206474355:A:G	K38E	0.998
1:206476199:T:C	L126P	0.998
1:206476226:A:G	D135G	0.998
1:206476227:C:A	D135E	0.998
1:206476227:C:G	D135E	0.998

dbSNP variants (sampled 300 via entrez): RS1000006689 (1:206491396 G>A), RS1000127807 (1:206485405 C>G,T), RS1000180372 (1:206485222 A>C,T), RS1000417815 (1:206474199 C>G,T), RS1000516208 (1:206486480 G>A), RS1000692124 (1:206481659 C>T), RS1000749477 (1:206475223 T>C), RS1000756535 (1:206479770 G>A), RS1000932178 (1:206470145 T>C), RS1001347636 (1:206485774 G>A), RS1001462448 (1:206485959 C>T), RS1001629079 (1:206480753 G>A), RS1001640842 (1:206474597 T>A), RS1001929353 (1:206480378 A>G), RS1003758102 (1:206471730 C>T)

Disease associations

OMIM: gene MIM:605048 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
encephalitis, acute, infection-induced, susceptibility to	Moderate	Autosomal dominant

Mondo (1): encephalitis, acute, infection-induced, susceptibility to (MONDO:0800174)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003622_12	Systemic lupus erythematosus	1.000000e-11
GCST003622_3	Systemic lupus erythematosus	2.000000e-07
GCST004346_25	Psoriasis	2.000000e-08
GCST004627_134	Lymphocyte count	1.000000e-15
GCST009391_1588	Metabolite levels	6.000000e-07
GCST011956_61	Systemic lupus erythematosus	2.000000e-10
GCST90002381_14	Eosinophil count	6.000000e-11
GCST90002382_24	Eosinophil percentage of white cells	2.000000e-12
GCST90002388_642	Lymphocyte count	7.000000e-22
GCST90002389_95	Lymphocyte percentage of white cells	6.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0010350	cholesteryl ester 22:6 measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3038486 (PROTEIN COMPLEX), CHEMBL3529 (SINGLE PROTEIN), CHEMBL4296146 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 195,716 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1096	AMLEXANOX	4	4,195
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL1980297	ILORASERTIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL564829	MILCICLIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL1090479	GSK-1070916	1
CHEMBL1908397	KW-2449	1
CHEMBL3128043	PF-03758309	1
CHEMBL3545083	RGB-286638	1

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12142086	Toxicity	3	gefitinib	Exanthema;Non-Small Cell Lung Carcinoma
rs2151222	Toxicity	3	gefitinib	Diarrhea;Non-Small Cell Lung Carcinoma
rs3748022	Toxicity	3	gefitinib	Exanthema;Non-Small Cell Lung Carcinoma

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12142086	IKBKE	3	2.50	1	gefitinib
rs2151222	IKBKE	3	2.50	1	gefitinib
rs1953090	IKBKE		0.00	0
rs3748022	IKBKE	3	2.00	1	gefitinib

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — IKK family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
BAY-985	Inhibition	8.7	pIC50
SR8185	Inhibition	8.52	pIC50
MPI-0485520	Inhibition	8.52	pIC50
compound 17d [PMID: 23099093]	Inhibition	7.52	pIC50
BX-795	Inhibition	7.39	pIC50
compound II [PMID: 21329883]	Inhibition	7.23	pIC50
MRT67307	Inhibition	6.8	pIC50
GSK8612	Inhibition	6.1	pKd
amlexanox	Inhibition	6.0	pIC50

Binding affinities (BindingDB)

1082 measured of 1377 human assays (1378 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[2-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-2-(oxan-4-yloxy)benzonitrile	IC50	0.29 nM	US-10072001: Tank-binding kinase inhibitor compounds
2-[(3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl]oxy-5-[6-[3-methoxy-4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]benzonitrile	IC50	0.481 nM	US-10259811: Tank-binding kinase inhibitor compounds
2-[3,3-difluoro-1-(2-hydroxyacetyl)piperidin-4-yl]oxy-5-[6-[3-methoxy-4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]benzonitrile	IC50	0.687 nM	US-10072001: Tank-binding kinase inhibitor compounds
2-(oxan-4-yloxy)-5-[2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]benzonitrile	IC50	0.71 nM	US-10072001: Tank-binding kinase inhibitor compounds
5-[2-[4-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-2-(oxan-4-yloxy)benzonitrile	IC50	0.77 nM	US-10072001: Tank-binding kinase inhibitor compounds
2-(oxan-4-yloxy)-5-[2-(4-piperazin-1-ylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]benzonitrile	IC50	0.81 nM	US-10072001: Tank-binding kinase inhibitor compounds
2-[1-(2-hydroxyacetyl)piperidin-4-yl]oxy-5-[8-[4-(4-methylpiperazin-1-yl)phenyl]-7H-purin-6-yl]benzonitrile	IC50	0.815 nM	US-10072001: Tank-binding kinase inhibitor compounds
2-[1-(2-hydroxyacetyl)piperidin-4-yl]oxy-5-[6-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]benzonitrile	IC50	0.851 nM	US-10072001: Tank-binding kinase inhibitor compounds
2-(oxan-4-yloxy)-5-[2-[(4-piperidin-4-yl-2-pyridinyl)amino]-4-pyridinyl]benzonitrile	IC50	1 nM	US-8969335: Benzonitrile derivatives as kinase inhibitors
5-(4-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)-2-((tetrahydro-2H-pyran-4-yl)oxy)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
5-(4-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)-2-((tetrahydro-2H-pyran-4-yl)oxy)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
5-(4-((4-(piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)-2-((tetrahydro-2H-pyran-4-yl)oxy)benzonitrile, trifluoroacetic acid salt	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-((S)-5-oxopyrrolidine-2-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1H-1,2,3-triazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(4H-1,2,4-triazole-3-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1H-pyrazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1H-imidazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1-methyl-1H-1,2,3-triazole-4-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-((3,3-difluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
(R)-2-((3,3-difluoro-1-(2- hydroxyacetyl)piperidin-4- yl)oxy)-5-(4-((4-(4-(oxetan- 3-yl)piperazin-1- yl)phenyl)amino)-1,3,5- triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-((S)-2- hydroxypropanoyl)piperidin- 4-yl)oxy)-5-(4-((4-(4- (oxetan-3-yl)piperazin-1- yl)phenyl)amino)-1,3,5- triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
(S)-2-((3,3-difluoro-1-(1H-pyrazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
(S)-2-((3,3-difluoro-1-(1H-1,2,3-triazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((4R,5S)-5-fluoro-1-(2- hydroxyacetyl)-3,3- dimethylpiperidin-4- yl)oxy)-5-(4-((4-(4-(oxetan- 3-yl)piperazin-1- yl)phenyl)amino)-1,3,5- triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-((R)-2-(hydroxymethyl)morpholino)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-(hydroxymethyl)morpholino)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-(hydroxymethyl)morpholino)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((3-fluoro-4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-((R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-((R)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-((R)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1H-imidazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1H-pyrazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-(1H-1,2,3-triazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-(1H-imidazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((S)-3,3-difluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-((S)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-formylpiperidin-4-yl)oxy)-5-(4-((3-fluoro-4-(piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(2-hydroxyacetyl)piperidin-4-yl)oxy)-5-(4-((3-fluoro-4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-ylmethyl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-(1-(oxetan-3-yl)piperidin-4-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
4-(4-((4-(3-cyano-4-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)phenyl)-1,3,5-triazin-2-yl)amino)phenyl)morpholine-2-carboxamide	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((4-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-(1H-pyrazole-5-carbonyl)piperidin-4-yl)oxy)-5-(4-((4-(1-(oxetan-3-yl)piperidin-4-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds
2-(((3R,4S)-3-fluoro-1-((S)-2-hydroxypropanoyl)piperidin-4-yl)oxy)-5-(4-((3-methoxy-4-(4-morpholinopiperidin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile	IC50	1 nM	US-10253019: Tank-binding kinase inhibitor compounds

ChEMBL bioactivities

540 potent at pChembl≥5 of 590 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.199	nM	STAUROSPORINE
9.44	IC50	0.365	nM	STAUROSPORINE
9.36	IC50	0.439	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL3682430
8.70	IC50	2	nM	CHEMBL3687186
8.70	IC50	2	nM	CHEMBL4566796
8.70	IC50	2	nM	BAY-985
8.40	IC50	4	nM	CHEMBL2011940
8.40	IC50	4	nM	CHEMBL3682423
8.40	IC50	4	nM	CHEMBL3682431
8.40	IC50	4	nM	CHEMBL4436188
8.40	IC50	4	nM	CHEMBL4538751
8.40	IC50	4	nM	CHEMBL4454902
8.30	IC50	5	nM	CHEMBL2011932
8.30	IC50	5	nM	CHEMBL3639859
8.30	IC50	5	nM	CHEMBL3687181
8.30	Ki	5.012	nM	CHEMBL1980995
8.29	Kd	5.1	nM	STAUROSPORINE
8.22	IC50	6	nM	CHEMBL3682420
8.22	IC50	6	nM	CHEMBL3687175
8.22	IC50	6	nM	CHEMBL3682434
8.22	IC50	6	nM	CHEMBL3682427
8.22	IC50	6	nM	CHEMBL4435393
8.15	IC50	7	nM	CHEMBL3682428
8.15	IC50	7	nM	CHEMBL3687159
8.15	IC50	7	nM	CHEMBL4468020
8.15	IC50	7.1	nM	CHEMBL4568087
8.10	IC50	8	nM	CHEMBL3687125
8.10	IC50	8	nM	CHEMBL3687129
8.10	IC50	8	nM	CHEMBL3687128
8.10	IC50	8	nM	CHEMBL3687132
8.10	IC50	8	nM	CHEMBL3687121
8.06	IC50	8.7	nM	CHEMBL4227907
8.05	IC50	9	nM	CHEMBL2011942
8.00	IC50	10	nM	CHEMBL3682429
8.00	IC50	10	nM	CHEMBL3687111
8.00	IC50	10	nM	CHEMBL3687185
8.00	IC50	10	nM	CHEMBL4594167
8.00	IC50	10	nM	CHEMBL4453292
7.96	Kd	11	nM	LESTAURTINIB
7.92	IC50	12	nM	CHEMBL3682433
7.89	IC50	13	nM	CHEMBL3687160
7.89	Kd	13	nM	R-406
7.85	IC50	14	nM	CHEMBL3950168
7.82	IC50	15	nM	CHEMBL3687183
7.82	IC50	15	nM	CHEMBL3687151
7.82	IC50	15	nM	CHEMBL4515413
7.80	IC50	16	nM	CHEMBL4552254
7.77	IC50	17	nM	CHEMBL2011941
7.77	IC50	17	nM	CHEMBL4459120

PubChem BioAssay actives

278 with measured affinity, of 1575 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
(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	1715316: Inhibition of human IKKepsilon using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0002	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119786: Inhibition of IKKepsilon (unknown origin)	ic50	0.0010	uM
1-[4-[(1R)-1-[2-[[6-[6-(dimethylamino)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0020	uM
3,3,3-trifluoro-1-[4-[(1R)-1-[2-[[6-[6-(methoxymethyl)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0020	uM
3,3,3-trifluoro-1-[4-[(1R)-1-[2-[[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0040	uM
1-[4-[(1R)-1-[2-[[6-[1-(cyclobutylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0040	uM
1-[4-[(1R)-1-[2-[[6-[6-(cyclopropylmethoxy)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0040	uM
N-[3-[[2-(3-aminophenyl)-6-bromo-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclobutanecarboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0040	uM
1-(aminomethyl)-N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopropane-1-carboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0050	uM
1-[4-[(1R)-1-[2-[[6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0060	uM
1-[4-[[2-[[6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0070	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637086: Inhibition of full-length recombinant human GST-tagged IKK-epsilon expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0071	uM
(2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388078: Inhibition of IKKepsilon (unknown origin)	ic50	0.0087	uM
7-[3-(cyclobutanecarbonylamino)propylamino]-2-[4-(2-piperidin-1-ylethoxy)phenyl]-1H-imidazo[4,5-b]pyridine-6-carboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0090	uM
1-[4-[[2-[[6-[6-(dimethylamino)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0100	uM
3,3,3-trifluoro-1-[4-[[2-[[6-[6-(methylamino)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0100	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637086: Inhibition of full-length recombinant human GST-tagged IKK-epsilon expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0100	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637086: Inhibition of full-length recombinant human GST-tagged IKK-epsilon expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0100	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507566: Binding affinity to IKK-epsilon	kd	0.0110	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625074: Binding constant for IKK-epsilon kinase domain	kd	0.0130	uM
3,3,3-trifluoro-1-[4-[[2-[[6-(2-methyl-4-pyridinyl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0150	uM
3,3,3-trifluoro-1-[4-[[2-[[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0160	uM
2-[[4-[[4-(3,3,3-trifluoropropanoyl)piperazin-1-yl]methyl]-2-pyridinyl]amino]-3H-benzimidazole-5-carbonitrile	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0170	uM
N-[3-[[6-bromo-2-[4-(2-piperidin-1-ylethoxy)phenyl]-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclobutanecarboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0170	uM
N-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0180	uM
N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]-N-methylcyclobutanecarboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0200	uM
N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclobutanecarboxamide	1075340: Inhibition of IKK-epsilon (unknown origin) using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0210	uM
5-[5-(3-hydroxypropoxy)-6-methoxybenzimidazol-1-yl]-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carbonitrile	1798806: IKK Kinase Inhibition Assay from Article 10.1016/j.bmcl.2006.09.018: “5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase.”	ic50	0.0250	uM
N-[3-[[5-cyclopropyl-2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	718570: Inhibition of IKKepsilon	ic50	0.0300	uM
1-[4-[[2-[[6-[2-(dimethylamino)-4-pyridinyl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0350	uM
3,3,3-trifluoro-1-[4-[(1R)-1-[2-[[6-(3-methyl-1,2,4-oxadiazol-5-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0370	uM
5-(5,6-dimethoxybenzimidazol-1-yl)-3-[(2-methylsulfonylphenyl)methoxy]thiophene-2-carbonitrile	276909: Inhibition of human recombinant IKKepsilon by TR-FRET assay	ic50	0.0398	uM
1-[4-[[2-[[6-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0410	uM
2-[7-[3-(cyclopentanecarbonylamino)propylamino]-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]-1,3-thiazole-4-carboxamide	1075340: Inhibition of IKK-epsilon (unknown origin) using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0420	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526271: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged IKBKE (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0440	uM
7-[3-(cyclopentanecarbonylamino)propylamino]-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridine-6-carboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0460	uM
N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]-3-hydroxycyclobutane-1-carboxamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0460	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide	1637086: Inhibition of full-length recombinant human GST-tagged IKK-epsilon expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0480	uM
5-[6-methoxy-5-(2-morpholin-4-ylethoxy)benzimidazol-1-yl]-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carbonitrile	1798806: IKK Kinase Inhibition Assay from Article 10.1016/j.bmcl.2006.09.018: “5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase.”	ic50	0.0500	uM
Bosutinib	625074: Binding constant for IKK-epsilon kinase domain	kd	0.0530	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526271: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged IKBKE (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0580	uM
N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]-2,2-dimethylpropanamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0600	uM
2-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-5-ethyl-1,3,4-oxadiazole	1992895: Inhibition of human recombinant IKKepsilon by microfluidic mobility shift assay	ic50	0.0700	uM
N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide	1075340: Inhibition of IKK-epsilon (unknown origin) using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0760	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148581: Binding affinity to human IKBKE incubated for 45 mins by Kinobead based pull down assay	kd	0.0765	uM
N-(cyclopropylmethyl)-2-[[4-[[4-(3,3,3-trifluoropropanoyl)piperazin-1-yl]methyl]-2-pyridinyl]amino]-3H-benzimidazole-5-carboxamide	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0800	uM
N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]-2-methylpropanamide	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0840	uM
3,3,3-trifluoro-1-[4-[[2-[[6-[3-(2-methylpropyl)-1,2,4-oxadiazol-5-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]propan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0890	uM
2-(3-aminophenyl)-6-bromo-N-methyl-1H-imidazo[4,5-b]pyridin-7-amine	654912: Inhibition of Ikkepsilon using 5FAM-AKELDQGSLCTpSFVGTLQ-NH2 as substrate by microfluidic mobility shift assay	ic50	0.0930	uM
1-[4-[[2-[[6-(1-ethylpyrazol-4-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582162: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay	ic50	0.0980	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation, increases mutagenesis	4
(+)-JQ1 compound	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Smoke	increases abundance, decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
GSK-J4	decreases expression	1
tempol	decreases expression	1
triphenyl phosphate	affects expression	1
brilliant green	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
nickel chloride	decreases expression	1
diallyl trisulfide	decreases reaction, increases expression	1
amlexanox	decreases activity	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
motexafin gadolinium	affects cotreatment, increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
BX795	decreases activity	1
Aripiprazole	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Allergens	increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Daunorubicin	affects response to substance	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

359 unique, capped per target: 356 binding, 2 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1942749	Binding	Inhibition of human IKKepsilon/TBK1 in HL-60 cells lysate assessed as reduction of labeling of acyl-phosphate ATP probe at 100 nM	6-Position optimization of tricyclic 4-quinolone-based inhibitors of glycogen synthase kinase-3β: discovery of nitrile derivatives with picomolar potency. — Bioorg Med Chem Lett
CHEMBL1964108	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: IKBKE	PubChem BioAssay data set
CHEMBL4407594	ADMET	Inhibition of recombinant human full-length GST-tagged IKBKE expressed in baculovirus expression system at 25 uM using FRET-labeled Ser/Thr 11 peptide as substrate measured after 1 hr by Z’-lyte assay relative to control	Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase. — J Med Chem

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8AZ	THP1-Dual KO-IKKepsilon	Cancer cell line	Male
CVCL_B8I5	Abcam HCT 116 IKBKE KO	Cancer cell line	Male
CVCL_B9KE	Abcam A-549 IKBKE KO	Cancer cell line	Male
CVCL_D2FT	Abcam MCF-7 IKBKE KO	Cancer cell line	Female
CVCL_D7RX	Ubigene A-549 IKBKE KO	Cancer cell line	Male
CVCL_D9GW	Ubigene HEK293 IKBKE KO	Transformed cell line	Female
CVCL_SS38	HAP1 IKBKE (-) 1	Cancer cell line	Male
CVCL_SS39	HAP1 IKBKE (-) 2	Cancer cell line	Male
CVCL_VC57	BIONi010-C-19	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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