CHUK

Summary

CHUK (component of inhibitor of nuclear factor kappa B kinase complex, HGNC:1974) is a protein-coding gene on chromosome 10q24.31, encoding Inhibitor of nuclear factor kappa-B kinase subunit alpha (O15111). Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses.

This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor.

Source: NCBI Gene 1147 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cocoon syndrome (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 287 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1974
Approved symbol	CHUK
Name	component of inhibitor of nuclear factor kappa B kinase complex
Location	10q24.31
Locus type	gene with protein product
Status	Approved
Aliases	IKK1, IKK-alpha, IkBKA, NFKBIKA, IKKA
Ensembl gene	ENSG00000213341
Ensembl biotype	protein_coding
OMIM	600664
Entrez	1147

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000370397, ENST00000585551, ENST00000588656, ENST00000590930, ENST00000896937, ENST00000896938

RefSeq mRNA: 2 — MANE Select: NM_001278 NM_001278, NM_001320928

CCDS: CCDS7488

Canonical transcript exons

ENST00000370397 — 21 exons

Exon	Start	End
ENSE00000720783	100217995	100218130
ENSE00000720798	100218718	100218825
ENSE00000720802	100219008	100219132
ENSE00000720806	100219270	100219359
ENSE00000720811	100220588	100220676
ENSE00000811331	100199971	100200020
ENSE00000811332	100200671	100200780
ENSE00000811333	100202088	100202149
ENSE00000987237	100209595	100209789
ENSE00000987238	100207230	100207332
ENSE00000987239	100205076	100205199
ENSE00000987240	100204506	100204657
ENSE00000987241	100194425	100194521
ENSE00000987242	100193984	100194131
ENSE00000987243	100193298	100193431
ENSE00001121698	100222112	100222181
ENSE00001121704	100222866	100222980
ENSE00001121713	100225923	100226017
ENSE00001452611	100229428	100229596
ENSE00002791563	100188300	100189627
ENSE00003487938	100190869	100190968

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 94.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1576 / max 163.3760, expressed in 1798 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111026	18.1576	1798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.45	gold quality
middle frontal gyrus	UBERON:0002702	94.23	gold quality
oocyte	CL:0000023	92.01	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.06	gold quality
islet of Langerhans	UBERON:0000006	90.77	gold quality
endometrium epithelium	UBERON:0004811	89.24	gold quality
palpebral conjunctiva	UBERON:0001812	88.94	gold quality
germinal epithelium of ovary	UBERON:0001304	88.81	gold quality
gingival epithelium	UBERON:0001949	88.71	gold quality
monocyte	CL:0000576	88.48	gold quality
mononuclear cell	CL:0000842	88.14	gold quality
leukocyte	CL:0000738	87.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.21	gold quality
calcaneal tendon	UBERON:0003701	86.94	gold quality
rectum	UBERON:0001052	86.63	gold quality
choroid plexus epithelium	UBERON:0003911	85.90	gold quality
gastrocnemius	UBERON:0001388	85.87	gold quality
visceral pleura	UBERON:0002401	85.80	gold quality
muscle of leg	UBERON:0001383	85.49	gold quality
jejunal mucosa	UBERON:0000399	85.48	gold quality
pancreas	UBERON:0001264	85.47	gold quality
epithelium of nasopharynx	UBERON:0001951	85.46	gold quality
gingiva	UBERON:0001828	85.42	gold quality
metanephric glomerulus	UBERON:0004736	85.07	gold quality
renal glomerulus	UBERON:0000074	84.97	gold quality
stromal cell of endometrium	CL:0002255	84.58	gold quality
cortex of kidney	UBERON:0001225	84.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.54	gold quality
adrenal tissue	UBERON:0018303	84.39	gold quality
nephron tubule	UBERON:0001231	84.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL11B, ETS1, FOSL1, IRF3, JUNB, MYC, NCOA3, NFKB2, NFKBIA, NFKBIB, OVOL1, RELA, RELB, RUNX3, TP53, TP63, USF1, USF2

miRNA regulators (miRDB)

115 targeting CHUK, 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-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Literature-anchored findings (GeneRIF, showing 40)

• difference of kinetic mechanisms of heterodimer with IKK-2 compared with IKK and TBK-1 (PMID:11815618)
• TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. (PMID:11864612)
• activity is comparable in normal B cells and B-CLL lymphocytes and is not involved in up-regulation of TRAF1 in B-CLL (PMID:12411322)
• TNFalpha activation of the NF-kappaB pathway is associated with the inducible binding of TAK1 to TRAF2 and both IKKalpha and IKKbeta (PMID:12547194)
• IKKalpha and IKKbeta may alter their substrate and signaling specificities to regulate mitogen-induced DNA synthesis through distinct mechanisms (PMID:12589056)
• IKKalpha involved in COX-2 induction in colorectal tumors (PMID:12771929)
• New nuclear role of IKK-alpha in modifying histone function that is critical for the activation of NF-kappaB-directed gene expression (PMID:12789342)
• noncoordinate expression of I kappa B kinases plays a role in determining the cell type-specific role of Akt in NF-kappa B activation. (PMID:14585846)
• in response to HTLV-1 Tax, IKK2 plays a dominant role in signaling for IkappaBalpha degradation, whereas IKK1 appears to play an important role in enhancing the transcriptional activity of NF-kappaB by promoting RelA/p65 phosphorylation. (PMID:14963024)
• IKK-alpha controls skeletal and craniofacial morphogenesis by repressing expression of fibroblast growth factor (FGF) family members, such as FGF8, whose expression is specifically elevated in the limb bud ectoderm of IKK-alpha-deficient mice (PMID:15071597)
• IkappaB kinase alpha (IKKalpha) docks to p100 in NF-kappaB-inducing kinase-induced phosphorylation (PMID:15140882)
• IKK complex is constitutively activated in ATL cells through a cellular mechanism distinct from that of Tax-mediated IKK activation (PMID:15153339)
• Data demonstrate a master regulatory role of IkappaB kinase (IKK)/NF-kappaB signaling for immediate-early gene induction after lipopolysaccharide engagement in precursor B cells. (PMID:15226448)
• proximal 5’-flanking region of the IKKalpha gene contains a functional promoter reciprocally regulated by p53 and ETS-1 (PMID:15469934)
• 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)
• IkappaB kinase alpha has an essential role in the constitutive processing of NF-kappaB2 p100 (PMID:15677466)
• Estrogen treatment facilitated the association of IKKalpha, estrogen receptor alpha, and AIB1/SRC-3 to estrogen-responsive promoters. (PMID:15808510)
• Findings unveil a hitherto unsuspected mode of activation for the IKK/IkappaB signaling cascade within the cell nucleus of neutrophils (PMID:16034126)
• IkappaB kinase and IkappaBalpha have NF-kappaB-dependent as well as NF-kappaB-independent pathways of HAS1 activation (PMID:16258173)
• LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway) (PMID:16280329)
• Gly-Cl & HOCl oxidaized IkappaBalpha methionine when added to the cells in Hanks buffer. In contrast,Tau-Cl (1 mM) in Hanks buffer had no effect. However, Tau-Cl in full medium did modify IkappaBalpha. (PMID:16405428)
• IKK alpha influences estrogen-mediated cell cycle progression through its regulation of E2F1. (PMID:16407216)
• These results altogether suggest that Fhit functions as an anti-oncoprotein by inhibiting the phosphorylation of IkappaB-alpha and thereby blocking NF-kappaB signaling. (PMID:16733051)
• IKKalpha regulates growth pathway involving the p52/RelB-dependent transcriptional regulation of the skp2 gene. (PMID:16902410)
• overexpression of IKKalpha in the epidermis antagonized chemical carcinogen-induced mitogenic and angiogenic activities, repressing tumor progression and metastases (PMID:17079494)
• IKKalpha was found to be associated with Aurora A in the centrosome and regulate Aurora A phosphorylation at threonine residue 288, a site which is important in modulating its kinase activity. (PMID:17102620)
• cells with reduced IkappaBalpha expression are more susceptible to viral infection, with less apoptosis and more viral replication. IkappaBalpha thus acts as a sensor of viral infection (PMID:17138672)
• IkappaB kinase (IKK) alpha but not IKK beta relocalizes to cellular hot spots in transformed Jurkat T cells. (PMID:17145747)
• IKK alpha and IKKbeta are distinctly involved in MUC5AC induction by S. pneumoniae via an ERK1-dependent mechanism (PMID:17237423)
• oxidative stress in endothelial cells created by excess of antioxidative agents resulted in the generation of reactive oxygen species, carbonylation and glutathionylation of proteins, inhibition of IKKalpha activity, and up-regulation of ICAM-1 (PMID:17237434)
• Selective inhibition of IkappaB kinase led to decreased c-FLIP expression and allowed all MCL samples to undergo TRAIL-mediated apoptosis (PMID:17237443)
• Data suggest that parthenolide inhibits IkappaB kinase, resulting in stabilization of cytoplasmic IkappaBalpha, which in turn leads to inhibition of NF-kappaB translocation and attenuation of subsequent inflammatory responses. (PMID:17272824)
• Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity. (PMID:17317777)
• The conformation of 24P-IkappaBalpha bound to beta-TrCP presents a bend corresponding to the 31DpSGLDpS36 motif and on both sides N- and C-terminal turn regions (Lys22-Asp31 and Met37-Glu43). (PMID:17319651)
• This study provides the biochemical and genetic evidence that phosphorylation of IKKalpha/beta and ubiquitination of NEMO are regulated by two distinct pathways upon T- cell receptor stimulation. (PMID:17363905)
• Study shows that Tax functions as an intracellular stimulator of an IKK-activating kinase, Tak1; in addition, Tax physically interacts with Tak1 and mediates the recruitment of IKK to Tak1. (PMID:17363973)
• Our results suggest that phosphorylation of CBP by IKKalpha regulates the CBP-mediated crosstalk between NF-kappaB and p53 and thus may be a critical factor in the promotion of cell proliferation and tumor growth. (PMID:17434128)
• Results indicate that antitumor and anti-inflammatory activities previously assigned to butein may be mediated in part through the direct inhibition of IKK, leading to the suppression of the NF-kappaB activation pathway. (PMID:17439942)
• nuclear IKK-alpha-mediated accumulation of p73alpha is one of the novel molecular mechanisms to induce apoptotic cell death in response to CDDP, which may be particularly important in killing tumor cells with p53 mutation (PMID:17452332)
• These results suggest that NF-kappaB and IKK signals via Ca(2+) influx and mitochondrial ROI play a role in the up-regulation of chemokine expression in eosinophils stimulated with H. pylori VacA. (PMID:17452475)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chuk	ENSDARG00000011662
mus_musculus	Chuk	ENSMUSG00000025199
rattus_norvegicus	Chuk	ENSRNOG00000022485
drosophila_melanogaster	IKKbeta	FBGN0024222

Paralogs (3): IKBKB (ENSG00000104365), TBK1 (ENSG00000183735), IKBKE (ENSG00000263528)

Protein

Protein identifiers

Inhibitor of nuclear factor kappa-B kinase subunit alpha — O15111 (reviewed: O15111)

Alternative names: Conserved helix-loop-helix ubiquitous kinase, I-kappa-B kinase 1, Nuclear factor NF-kappa-B inhibitor kinase alpha, Transcription factor 16

All UniProt accessions (1): O15111

UniProt curated annotations — full annotation on UniProt →

Function. Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at ‘Ser-10’ that are subsequently acetylated at ‘Lys-14’ by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor. Phosphorylates RIPK1 at ‘Ser-25’ which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity.

Subunit / interactions. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14. Directly interacts with TRPC4AP. May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2. Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity. Interacts with PIAS1; this interaction induces PIAS1 phosphorylation. Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-dependent manner. Interacts with FOXO3. Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation. Interacts with LRRC14. Interacts with SASH1. Directly interacts with DDX3X after the physiological activation of the TLR7 and TLR8 pathways; this interaction enhances CHUK autophosphorylation. (Microbial infection) Interacts with InlC of Listeria monocytogenes.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated. Ubiquitinated by TRIM56 via ‘Lys-63’-linked ubiquitination, promoting activation of CHUK/IKKA. (Microbial infection) Acetylation of Thr-179 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.

Disease relevance. Cocoon syndrome (COCOS) [MIM:613630] A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. The disease is caused by variants affecting the gene represented in this entry. Bartsocas-Papas syndrome 2 (BPS2) [MIM:619339] An autosomal recessive, severe form of popliteal pterygium syndrome. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but they are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Activated when phosphorylated and inactivated when dephosphorylated.

Domain organisation. The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG.

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

RefSeq proteins (2): NP_001269, NP_001307857 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR022007	IKKbetaNEMObind	Domain
IPR041185	IKBKB_SDD	Domain
IPR046375	IKBKB_SDD_sf	Homologous_superfamily
IPR051180	IKK	Family

Pfam: PF00069, PF12179, PF18397

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 (28 total): mutagenesis site 7, sequence conflict 5, modified residue 4, sequence variant 3, region of interest 2, helix 2, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3BRT	X-RAY DIFFRACTION	2.25
5EBZ	X-RAY DIFFRACTION	4.5
5TQY	ELECTRON MICROSCOPY	5.2
5TQX	ELECTRON MICROSCOPY	5.4
5TQW	ELECTRON MICROSCOPY	5.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15111-F1	84.41	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): 144 (proton acceptor)

Ligand- & substrate-binding residues (2): 21–29; 44

Post-translational modifications (4): 180, 23, 176, 179

Mutagenesis-validated functional residues (7):

Position	Phenotype
23	loss of phosphorylation and decrease of kinase activity.
44	loss of kinase activity.
44	loss of autophosphorylation.
176	loss of phosphorylation and of activity.
176	full activation.
179	no change in phosphorylation.
180	no change in phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1236974	ER-Phagosome pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1
R-HSA-198323	AKT phosphorylates targets in the cytosol
R-HSA-202424	Downstream TCR signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5602636	IKBKB deficiency causes SCID
R-HSA-5603027	IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
R-HSA-5603029	IkBA variant leads to EDA-ID
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5676590	NIK–>noncanonical NF-kB signaling
R-HSA-5684264	MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-9020702	Interleukin-1 signaling
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-933543	NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-937039	IRAK1 recruits IKK complex
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975144	IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
R-HSA-9758274	Regulation of NF-kappa B signaling
R-HSA-9833482	PKR-mediated signaling
R-HSA-9860276	SLC15A4:TASL-dependent IRF5 activation
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB gene sets: 555 (showing top): PID_BCR_5PATHWAY, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, BIOCARTA_TNFR2_PATHWAY, ELVIDGE_HYPOXIA_DN, BIOCARTA_RELA_PATHWAY, TAATAAT_MIR126, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, BIOCARTA_RNA_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (30): skeletal muscle contraction (GO:0003009), autophagy (GO:0006914), inflammatory response (GO:0006954), immune response (GO:0006955), integrin-mediated signaling pathway (GO:0007229), canonical NF-kappaB signal transduction (GO:0007249), response to xenobiotic stimulus (GO:0009410), response to virus (GO:0009615), response to toxic substance (GO:0009636), anatomical structure morphogenesis (GO:0009653), response to acetate (GO:0010034), negative regulation of autophagy (GO:0010507), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), positive regulation of interferon-alpha production (GO:0032727), response to hydroperoxide (GO:0033194), tumor necrosis factor-mediated signaling pathway (GO:0033209), toll-like receptor 4 signaling pathway (GO:0034142), non-canonical NF-kappaB signal transduction (GO:0038061), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), response to amino acid (GO:0043200), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), striated muscle cell differentiation (GO:0051146), response to cholecystokinin (GO:0061847), cellular response to tumor necrosis factor (GO:0071356), cellular response to virus (GO:0098586), pattern recognition receptor signaling pathway (GO:0002221), regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), IkappaB kinase activity (GO:0008384), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), scaffold protein binding (GO:0097110), transferrin receptor binding (GO:1990459), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), IkappaB kinase complex (GO:0008385), cytoplasmic side of plasma membrane (GO:0009898), CD40 receptor complex (GO:0035631), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
Diseases associated with the TLR signaling cascade	3
Toll Like Receptor 3 (TLR3) Cascade	2
Interleukin-1 signaling	2
TNF signaling	2
Downstream signaling events of B Cell Receptor (BCR)	1
Antigen processing-Cross presentation	1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
ZBP1(DAI) mediated induction of type I IFNs	1
PIP3 activates AKT signaling	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
MyD88 cascade initiated on plasma membrane	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular signaling cassette	2
response to chemical	2
response to oxygen-containing compound	2
protein dimerization activity	2
binding	2
striated muscle contraction	1
musculoskeletal movement	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
defense response	1
immune system process	1
response to stimulus	1
cell surface receptor signaling pathway	1
response to other organism	1
developmental process	1
anatomical structure development	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
positive regulation of type I interferon production	1
interferon-alpha production	1
regulation of interferon-alpha production	1
response to oxidative stress	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
cell surface toll-like receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
response to acid chemical	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein serine/threonine kinase activity	1
I-kappaB phosphorylation	1

Protein interactions and networks

STRING

4190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHUK	IKBKG	Q9Y6K9	999
CHUK	TRAF6	Q9Y4K3	998
CHUK	TRAF3	Q13114	996
CHUK	ERC1	Q8IUD2	991
CHUK	MYD88	P78397	984
CHUK	IRAK1	P51617	983
CHUK	IKBKB	O14920	983
CHUK	NFKBIA	P25963	973
CHUK	HSP90AA1	P07900	973
CHUK	RELA	Q04206	969
CHUK	NFKB1	P19838	966
CHUK	NLRC5	Q86WI3	966
CHUK	HSP90AB1	P08238	956
CHUK	RIPK1	Q13546	955
CHUK	TBK1	Q9UHD2	948

IntAct

285 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
IKBKG	IKBKB	psi-mi:“MI:0915”(physical association)	0.980
CHUK	IKBKG	psi-mi:“MI:0915”(physical association)	0.980
IKBKG	CHUK	psi-mi:“MI:0915”(physical association)	0.980
IKBKB	CHUK	psi-mi:“MI:0914”(association)	0.960
IKBKB	CHUK	psi-mi:“MI:0915”(physical association)	0.960
CHUK	IKBKB	psi-mi:“MI:0915”(physical association)	0.960
CHUK	IKBKB	psi-mi:“MI:0914”(association)	0.960
CHUK	NFKBIA	psi-mi:“MI:0217”(phosphorylation reaction)	0.950
MAP3K14	CHUK	psi-mi:“MI:0217”(phosphorylation reaction)	0.950
NFKBIA	CHUK	psi-mi:“MI:0217”(phosphorylation reaction)	0.950

BioGRID (562): MTOR (Affinity Capture-Western), CHUK (Affinity Capture-Western), CHUK (Affinity Capture-Western), NFKBIA (Biochemical Activity), RELA (Biochemical Activity), CHUK (Co-purification), CHUK (Affinity Capture-Western), CHUK (Reconstituted Complex), CHUK (Affinity Capture-Western), CHUK (Affinity Capture-Western), CHUK (Affinity Capture-Western), CREBBP (Affinity Capture-Western), CREBBP (Biochemical Activity), CHUK (Affinity Capture-Western), CHUK (Reconstituted Complex)

ESM2 similar proteins: A2CI34, A2CI35, O14920, O15111, O18412, O43149, O88351, O93307, P29597, P52333, Q09178, Q13049, Q20CR4, Q28DZ1, Q4G3H4, Q4TVR5, Q4VSN1, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5RBH9, Q5SSH7, Q5U464, Q5ZJB4, Q60680, Q62137, Q63272, Q67E00, Q67E01, Q6GM53, Q6XUX0, Q6XUX1, Q6XUX2, Q6XUX3, Q6ZWQ0, Q8BMQ2, Q8BP74, Q8BUI3, Q8CH72

Diamond homologs: A0A509AQE6, A0A5K1K8H0, A2QHV0, A8WYE4, A8XQD5, D3ZHP7, F4I1N8, F4IRW0, F4JBP3, G5EGQ3, I1RNG8, O08678, O08679, O14920, O15111, O15865, O22932, O43293, O54784, O61267, O70150, O70405, O75385, O88351, O88764, O96017, P07313, P20689, P25323, P27448, P32866, P34101, P34947, P35465, P40376, P43249, P51957, P54739, Q03141, Q08E52

SIGNOR signaling

79 interactions.

A	Effect	B	Mechanism
CHUK	up-regulates	CREBBP	binding
CHUK	down-regulates	FOXO3	phosphorylation
ERC1	up-regulates	CHUK	binding
CHUK	up-regulates	NCOA3	phosphorylation
CHUK	“up-regulates activity”	RELA	phosphorylation
CHUK	down-regulates	NCOR2	phosphorylation
CHUK	down-regulates	CCND1	phosphorylation
CHUK	up-regulates	IRF7	phosphorylation
CHUK	up-regulates	CREBBP	phosphorylation
CHUK	“form complex”	IKK-complex	binding
CHUK	“down-regulates quantity by destabilization”	MAP3K14	phosphorylation
MAP3K14	“up-regulates activity”	CHUK	phosphorylation
CHUK	down-regulates	TSC2	phosphorylation
AKT1	up-regulates	CHUK	phosphorylation
AKT2	up-regulates	CHUK	phosphorylation
AKT3	up-regulates	CHUK	phosphorylation
CHUK	down-regulates	FOXA2	phosphorylation
CHUK	down-regulates	TRAF4	phosphorylation
CHUK	“down-regulates activity”	CYLD	phosphorylation
CHUK	“up-regulates activity”	CYLD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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
RIP-mediated NFkB activation via ZBP1	7	60.3×	2e-09
TRAF6 mediated NF-kB activation	7	41.0×	3e-08
TNF signaling	7	38.0×	5e-08
RHO GTPases activate PAKs	5	34.9×	8e-06
TAK1-dependent IKK and NF-kappa-B activation	9	34.7×	9e-10
TNFR1-induced proapoptotic signaling	6	33.8×	9e-07
TNFR1-induced NF-kappa-B signaling pathway	7	30.1×	2e-07
Regulation of necroptotic cell death	5	28.2×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	7	59.0×	5e-09
canonical NF-kappaB signal transduction	13	47.6×	4e-16
interleukin-1-mediated signaling pathway	5	40.1×	2e-05
negative regulation of cytokine production involved in inflammatory response	5	21.1×	4e-04
tumor necrosis factor-mediated signaling pathway	6	19.8×	9e-05
negative regulation of canonical NF-kappaB signal transduction	11	18.9×	5e-09
JNK cascade	5	13.6×	3e-03
obsolete positive regulation of NF-kappaB transcription factor activity	5	10.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	98
Likely benign	122
Benign	40

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1120043	NM_001278.5(CHUK):c.934-2A>G	Pathogenic
1391938	NM_001278.5(CHUK):c.427C>T (p.Arg143Ter)	Pathogenic
1459668	NM_001278.5(CHUK):c.1249C>T (p.Gln417Ter)	Pathogenic
8946	NM_001278.5(CHUK):c.1264C>T (p.Gln422Ter)	Pathogenic
4719494	NM_001278.5(CHUK):c.316-2A>G	Likely pathogenic
4728667	NM_001278.5(CHUK):c.475-2A>C	Likely pathogenic

SpliceAI

2774 predictions. Top by Δscore:

Variant	Effect	Δscore
10:100190868:CCAT:C	donor_gain	1.0000
10:100190965:CTCC:C	acceptor_gain	1.0000
10:100190967:CC:C	acceptor_gain	1.0000
10:100190968:CC:C	acceptor_gain	1.0000
10:100190969:C:CC	acceptor_gain	1.0000
10:100192534:T:TA	donor_gain	1.0000
10:100192591:T:TA	donor_gain	1.0000
10:100193297:CCCAT:C	donor_gain	1.0000
10:100193301:T:C	donor_gain	1.0000
10:100194128:CTTG:C	acceptor_gain	1.0000
10:100194517:GTGAT:G	acceptor_gain	1.0000
10:100194518:TGAT:T	acceptor_gain	1.0000
10:100194521:TC:T	acceptor_loss	1.0000
10:100194522:C:CC	acceptor_gain	1.0000
10:100199967:TTA:T	donor_loss	1.0000
10:100199969:ACCTG:A	donor_loss	1.0000
10:100200019:CC:C	acceptor_gain	1.0000
10:100200020:CC:C	acceptor_gain	1.0000
10:100200021:C:CC	acceptor_gain	1.0000
10:100200022:T:A	acceptor_loss	1.0000
10:100200664:T:TA	donor_gain	1.0000
10:100200669:A:AC	donor_gain	1.0000
10:100200669:A:G	donor_loss	1.0000
10:100200670:C:CC	donor_gain	1.0000
10:100200670:CA:C	donor_gain	1.0000
10:100200670:CAG:C	donor_gain	1.0000
10:100200670:CAGA:C	donor_gain	1.0000
10:100200670:CAGAG:C	donor_gain	1.0000
10:100200673:AGATT:A	donor_gain	1.0000
10:100200689:C:CA	donor_gain	1.0000

AlphaMissense

4938 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:100193997:A:G	L654P	1.000
10:100194000:A:G	L653P	1.000
10:100194007:A:G	W651R	1.000
10:100194007:A:T	W651R	1.000
10:100194020:C:A	R646S	1.000
10:100194020:C:G	R646S	1.000
10:100194021:C:G	R646T	1.000
10:100202126:A:G	W511R	1.000
10:100202126:A:T	W511R	1.000
10:100205143:C:G	A430P	1.000
10:100218101:A:G	L276P	1.000
10:100219038:G:T	P220H	1.000
10:100219047:C:T	G217E	1.000
10:100219074:C:T	G208E	1.000
10:100219075:C:A	G208W	1.000
10:100219079:G:C	S206R	1.000
10:100219079:G:T	S206R	1.000
10:100219081:T:G	S206R	1.000
10:100219084:A:G	W205R	1.000
10:100219084:A:T	W205R	1.000
10:100219089:T:A	D203V	1.000
10:100219089:T:G	D203A	1.000
10:100219090:C:G	D203H	1.000
10:100219271:A:G	L188P	1.000
10:100219274:T:C	Y187C	1.000
10:100219275:A:G	Y187H	1.000
10:100219283:G:A	T184I	1.000
10:100219286:C:T	G183E	1.000
10:100219287:C:G	G183R	1.000
10:100219287:C:T	G183R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008521 (10:100198246 A>G), RS1000110110 (10:100206050 C>G), RS1000141060 (10:100205754 C>G), RS1000198735 (10:100212342 G>C), RS1000233830 (10:100226736 G>C), RS1000285825 (10:100213352 C>T), RS1000303035 (10:100220794 C>G,T), RS1000369852 (10:100220364 A>G), RS1000522518 (10:100225613 C>G), RS1000567748 (10:100214264 T>C), RS1000595564 (10:100225275 G>A), RS1000632823 (10:100212567 A>G), RS1000768673 (10:100206239 A>C), RS1000789577 (10:100190092 G>A), RS1000976301 (10:100199312 T>C)

Disease associations

OMIM: gene MIM:600664 | disease phenotypes: MIM:619339, MIM:613630

GenCC curated gene-disease

Disease	Classification	Inheritance
cocoon syndrome	Definitive	Autosomal recessive
Bartsocas-Papas syndrome 2	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Bartsocas-Papas syndrome 2	Moderate	AR

Mondo (2): Bartsocas-Papas syndrome 2 (MONDO:0859154), cocoon syndrome (MONDO:0013334)

Orphanet (1): Fetal encasement syndrome (Orphanet:465824)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000085	Horseshoe kidney
HP:0000191	Accessory oral frenulum
HP:0000202	Orofacial cleft
HP:0000260	Wide anterior fontanel
HP:0000269	Prominent occiput
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000396	Overfolded helix
HP:0000568	Microphthalmia
HP:0000776	Congenital diaphragmatic hernia
HP:0000963	Thin skin
HP:0001060	Axillary pterygium
HP:0001539	Omphalocele
HP:0001558	Decreased fetal movement
HP:0001636	Tetralogy of Fallot
HP:0002101	Abnormal lung lobation
HP:0002650	Scoliosis
HP:0003577	Congenital onset
HP:0005105	Abnormal nasal morphology
HP:0005623	Absent ossification of calvaria
HP:0005650	2-5 finger cutaneous syndactyly
HP:0007957	Corneal opacity
HP:0009004	Hypoplasia of the musculature
HP:0009755	Ankyloblepharon
HP:0009756	Popliteal pterygium
HP:0009760	Antecubital pterygium
HP:0009816	Lower limb undergrowth
HP:0009824	Upper limb undergrowth
HP:0009881	Aplasia of distal finger phalanx

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000248_3	Liver enzyme levels	2.000000e-08
GCST004346_51	Psoriasis	2.000000e-09
GCST006867_92	Type 2 diabetes	1.000000e-09
GCST011991_2	Psoriasis or type 2 diabetes (trans-disease meta-analysis)	1.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2111328 (PROTEIN COMPLEX), CHEMBL3476 (SINGLE PROTEIN), CHEMBL3883298 (PROTEIN COMPLEX), CHEMBL4523969 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 388,574 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL384467	DEXAMETHASONE	4	279,102
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL475251	R-406	2	762
CHEMBL129857	AS-602868	1	93
CHEMBL1908397	KW-2449	1	622
CHEMBL536151	IMD-0354	1	469
CHEMBL574738	AST-487	1	451

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11591741	CHUK		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — IKK family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
BAY 61-3606	Inhibition	7.35	pKi
compound 47 [PMID: 28737909]	Inhibition	6.19	pKi
BMS-345541	Negative	5.4	pIC50
PHA-408	Inhibition	4.85	pIC50

Binding affinities (BindingDB)

148 measured of 177 human assays (177 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-methyl-4-[1-propan-2-yl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	6 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol	IC50	9 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-ethyl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	9 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
1-[2-[1-ethyl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]ethynyl]cyclopentan-1-ol	IC50	9 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-ethyl-5-(3-hydroxy-3-methylbut-1-ynyl)pyrrolo[2,3-c]pyridin-3-yl]-1H-pyrazole-5-carbonitrile	IC50	9 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-(2-hydroxy-2-methylpropyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol	IC50	10 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
1-[2-[1-(2-hydroxyethyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]ethynyl]cyclopentan-1-ol	IC50	14 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-methylsulfonyl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	14 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-(3-hydroxypropyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	16 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-(2-hydroxy-2-methylpropyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	18 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
1-[2-[3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl]ethynyl]cyclopentan-1-ol	IC50	19 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
1-[2-[1-methyl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]ethynyl]cyclopentan-1-ol	IC50	21 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-methyl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	28 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[5-(3-hydroxy-3-methylbut-1-ynyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-1-yl]-2-methylbutan-2-ol	IC50	29 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-ethyl-3-(5-methyl-1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	29 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-(3-methoxypropyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	45 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-(2-hydroxyethyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	47 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-pentan-3-yl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	48 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-(2-methylpropyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	55 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-pentan-2-yl-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	57 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[3-(5-amino-1H-pyrazol-4-yl)-1-ethylpyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	58 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	60 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-(1-methylpiperidin-4-yl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	65 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[5-(3-hydroxy-3-methylbut-1-ynyl)-1-(2-hydroxy-2-methylpropyl)pyrrolo[2,3-c]pyridin-3-yl]-1H-pyrazole-5-carbonitrile	IC50	68 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-(1-methylazetidin-3-yl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	76 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-amino-5-(pyridin-4-yl)-3-(4-sulfamoylphenyl)benzamide	IC50	79 nM
2-methyl-4-[1-(oxetan-3-ylmethyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	88 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
4-[1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	IC50	92 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
2-methyl-4-[1-(oxolan-3-ylmethyl)-3-(1H-pyrazol-4-yl)pyrrolo[2,3-c]pyridin-5-yl]but-3-yn-2-ol	IC50	129 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
(2-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}ethyl)urea	IC50	130 nM
amino-N-({3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}methyl)sulfonamide	IC50	170 nM
(2R)-2-amino-3-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}propanamide	IC50	190 nM
4-[3-(aminomethyl)phenyl]-N,12-dimethyl-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-8-amine	IC50	220 nM
4-(1-benzyl-3-pyrazolidin-4-ylpyrrolo[2,3-c]pyridin-5-yl)-2-methylbut-3-yn-2-ol	IC50	224 nM	US-9981963: 3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridine derivatives as NIK inhibitors
N,12-dimethyl-11,14,17-triazatetracyclo[8.7.0.0^{3,8}.0^{11,15}]heptadeca-1,3,5,7,9,12,14,16-octaen-16-amine	IC50	230 nM
({3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}methyl)urea	IC50	260 nM
(2S)-2-amino-3-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}propanamide	IC50	260 nM
N,12-dimethyl-4-phenyl-5-oxa-3,7,10,12-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2(6),3,7,10-pentaen-8-amine	IC50	270 nM
2-amino-N-methyl-3-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}propanamide	IC50	330 nM
methyl[2-({12-methyl-11,14,17-triazatetracyclo[8.7.0.0^{3,8}.0^{11,15}]heptadeca-1,3,5,7,9,12,14,16-octaen-16-yl}amino)ethyl]amine	IC50	390 nM
2-[(2-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}ethyl)amino]acetamide	IC50	390 nM
2-amino-5-(4-chlorophenyl)-3-(4-sulfamoylphenyl)benzamide	IC50	398 nM
amino-N-(2-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}ethyl)sulfonamide	IC50	440 nM
(3-{8-[(2-aminoethyl)amino]-12-methyl-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl}phenyl)methanol	IC50	450 nM
2-amino-5-(4-fluorophenyl)-3-(4-sulfamoylphenyl)benzamide	IC50	501 nM
2-[({3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}methyl)amino]acetamide	IC50	510 nM
2-amino-3-{4-[(2-aminoethyl)sulfamoyl]phenyl}-5-phenylbenzamide	IC50	631 nM
4-[3-(2-aminoethyl)phenyl]-N,12-dimethyl-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-8-amine	IC50	650 nM
N,12-dimethyl-14,15,17-triazatetracyclo[8.7.0.0^{3,8}.0^{11,15}]heptadeca-1,3,5,7,9,11,13,16-octaen-16-amine	IC50	670 nM
2-{3-[12-methyl-8-(methylamino)-3-thia-1,7,10-triazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),4,7,9,11-pentaen-4-yl]phenyl}acetamide	IC50	680 nM

ChEMBL bioactivities

495 potent at pChembl≥5 of 545 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	DEXAMETHASONE
8.24	Kd	5.8	nM	STAUROSPORINE
8.22	IC50	6	nM	CHEMBL5866553
8.20	IC50	6.31	nM	CHEMBL2164412
8.20	IC50	6.31	nM	CHEMBL2164411
8.20	IC50	6.31	nM	CHEMBL2164410
8.15	IC50	7	nM	CHEMBL549478
8.15	IC50	7	nM	CHEMBL558491
8.10	IC50	7.943	nM	CHEMBL2164417
8.10	IC50	8	nM	CHEMBL551773
8.05	IC50	9	nM	CHEMBL5757104
8.05	IC50	9	nM	CHEMBL5770671
8.05	IC50	9	nM	CHEMBL5791598
8.05	IC50	9	nM	CHEMBL5758256
8.05	Kd	9	nM	LESTAURTINIB
8.00	IC50	10	nM	CHEMBL5819565
7.98	IC50	10.58	nM	CHEMBL4859206
7.97	IC50	10.59	nM	CHEMBL4859206
7.96	IC50	11	nM	CHEMBL1876217
7.96	IC50	11.02	nM	CHEMBL1876217
7.96	IC50	11	nM	CHEMBL562720
7.92	IC50	12	nM	CHEMBL562971
7.90	IC50	12.59	nM	CHEMBL483165
7.85	IC50	14	nM	CHEMBL552183
7.85	IC50	14	nM	CHEMBL5981304
7.85	IC50	14	nM	CHEMBL5984061
7.80	IC50	15.94	nM	CHEMBL4849098
7.80	IC50	16	nM	CHEMBL6049643
7.79	IC50	16.03	nM	CHEMBL4849098
7.75	IC50	18	nM	CHEMBL5868773
7.72	IC50	19	nM	CHEMBL5776090
7.68	IC50	21	nM	CHEMBL5826590
7.66	IC50	22	nM	CHEMBL562370
7.60	IC50	25.12	nM	CHEMBL2164413
7.60	IC50	25	nM	CHEMBL360077
7.60	IC50	25	nM	CHEMBL561447
7.55	IC50	28	nM	CHEMBL5786713
7.54	IC50	29	nM	CHEMBL6027353
7.54	IC50	29	nM	CHEMBL6051381
7.52	IC50	30	nM	CHEMBL382945
7.52	IC50	30	nM	CHEMBL199837
7.50	IC50	31.62	nM	CHEMBL2164415
7.50	IC50	31.62	nM	CHEMBL4128114
7.50	IC50	31.62	nM	CHEMBL482540
7.50	IC50	32	nM	CHEMBL551024
7.48	IC50	33	nM	CHEMBL590109
7.41	IC50	39	nM	CHEMBL560708
7.41	IC50	39	nM	STAUROSPORINE
7.40	IC50	40	nM	CHEMBL199837
7.40	IC50	40	nM	CHEMBL200106

PubChem BioAssay actives

526 with measured affinity, of 1960 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
Dexamethasone	2131646: Inhibition of IKKA (unknown origin)	ic50	0.0005	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	624832: Binding constant for IKK-alpha kinase domain	kd	0.0058	uM
N-(1,1-dioxothian-4-yl)-4-(2-ethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0063	uM
N-(1,1-dioxothian-4-yl)-4-(2-propan-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0063	uM
4-(2-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(1,1-dioxothian-4-yl)benzenesulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0063	uM
11-(3-fluorophenyl)-N,3-dimethyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-amine	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0070	uM
3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]benzonitrile	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0070	uM
N-(1,1-dioxothian-4-yl)-5-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyridine-2-sulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0079	uM
11-(3-methoxyphenyl)-N,3-dimethyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-amine	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0080	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	507564: Binding affinity to IKK-alpha	kd	0.0090	uM
2-[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]phenol	1778247: Inhibition of IKKalpha (unknown origin) by ADP-Glo kinase assay	ic50	0.0106	uM
11-[3-(aminomethyl)phenyl]-N,3-dimethyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-amine	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0110	uM
2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenol	1778247: Inhibition of IKKalpha (unknown origin) by ADP-Glo kinase assay	ic50	0.0110	uM
3-methoxy-N-[[3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]phenyl]methyl]propanamide	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0120	uM
N-(1,1-dioxothian-4-yl)-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	354255: Inhibition of human recombinant IKK1	ic50	0.0126	uM
N-[[3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]phenyl]methyl]acetamide	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0140	uM
2-(3-benzyl-1,2,4-oxadiazol-5-yl)phenol	1778247: Inhibition of IKKalpha (unknown origin) by ADP-Glo kinase assay	ic50	0.0159	uM
N’-[[3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]phenyl]methyl]butanediamide	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0220	uM
2-amino-6-(2-hydroxyphenyl)-4-piperidin-3-ylpyridine-3-carbonitrile	240499: Inhibition of I-kappa-B-kinase alpha	ic50	0.0250	uM
2-hydroxy-N-[[3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]phenyl]methyl]acetamide	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0250	uM
4-(2-tert-butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(1,1-dioxothian-4-yl)benzenesulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0251	uM
[4-[[4-[5-(3-amino-3-methylbutyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258073: Inhibitory activity against IKK1	ic50	0.0300	uM
[4-[[4-[5-(3-amino-3-ethylpentyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258073: Inhibitory activity against IKK1	ic50	0.0300	uM
4-[2-[4-(methanesulfonamido)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]benzamide	1494999: Inhibition of IKK1 (unknown origin)	ic50	0.0316	uM
N-(azetidin-3-yl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	354255: Inhibition of human recombinant IKK1	ic50	0.0316	uM
N-(1,1-dioxothian-4-yl)-4-(2-piperidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0316	uM
1-[3-[5-[4-(aminomethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]-3-[2-fluoro-4-(trifluoromethyl)phenyl]urea	419418: Inhibition of IKK1	ic50	0.0320	uM
5-(2-aminoethyl)-7-[7-(1-benzothiophen-2-yl)-1H-indazol-5-yl]pyrrolo[3,2-d]pyrimidin-2-amine	455853: Inhibition of IKK1	ic50	0.0330	uM
N-[[3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]phenyl]methyl]thiadiazole-4-carboxamide	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0390	uM
N,3-dimethyl-11-phenyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-amine	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0400	uM
[4-[[4-[5-(4-hydroxybutyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0400	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624832: Binding constant for IKK-alpha kinase domain	kd	0.0410	uM
11-(4-fluorophenyl)-N,3-dimethyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-amine	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0430	uM
11-(2-fluorophenyl)-N,3-dimethyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-amine	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0440	uM
[4-[[4-[5-(3-hydroxy-3-methylbutyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0500	uM
N-(2-hydroxyethyl)-4-[3-[(Z)-(4-hydroxy-3-oxo-1-benzofuran-2-ylidene)methyl]-1-methylpyrrolo[2,3-b]pyridin-4-yl]benzamide	473521: Inhibition of IKKalpha	ic50	0.0500	uM
N-(1,1-dioxothian-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	354255: Inhibition of human recombinant IKK1	ic50	0.0501	uM
N-(1,1-dioxothian-4-yl)-4-[2-(triazol-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]benzenesulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0501	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0700	uM
2-amino-5-pyridin-4-yl-3-(4-sulfamoylphenyl)benzamide	1798808: IKK Kinase Inhibition Assay from Article 10.1016/j.bmcl.2007.04.088: “The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases.”	ic50	0.0790	uM
2-(dimethylamino)-N-[[3-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]phenyl]methyl]acetamide	424472: Inhibition of IKK1-catalyzed phosphorylation of GST-tagged IkappaBalpha fusion protein by fluorescence polarization assay	ic50	0.0790	uM
4-[2-[4-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]benzamide	1494999: Inhibition of IKK1 (unknown origin)	ic50	0.0794	uM
4-[2-[4-[3-(dimethylamino)propylcarbamoyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]benzamide	1494999: Inhibition of IKK1 (unknown origin)	ic50	0.0794	uM
4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]benzamide	1494999: Inhibition of IKK1 (unknown origin)	ic50	0.0794	uM
N-(1,1-dioxothian-4-yl)-6-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyridine-3-sulfonamide	697978: Inhibition of IKK1 in presence of 1 uM ATP	ic50	0.0794	uM
4-(2-amino-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamide	1458164: Inhibition of recombinant human N-terminal GST-tagged IKKalpha (1 to 745 residues) expressed in baculovirus expression system using biotinylated IkBalpha as substrate after 60 mins by DELFIA	ki	0.0800	uM
6,8-dichloro-7-(cyclopropylmethoxy)-9H-pyrido[3,4-b]indole	91701: Inhibitory activity against IkappaB kinase(IKK) isolated from HeLa cells activated with recombinant MEEK1 in an ELISA phosphorylation assay.	ic50	0.0800	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]phenyl]-[4-(dimethylamino)piperidin-1-yl]methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0800	uM
3-amino-6-(4-aminopiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide	447735: Inhibition of IKKalpha	ic50	0.0900	uM
4-[2-[2-methyl-3-(morpholin-4-ylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]benzamide	1494999: Inhibition of IKK1 (unknown origin)	ic50	0.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases reaction, affects reaction, decreases reaction, increases phosphorylation, increases activity (+1 more)	7
Quercetin	affects cotreatment, increases expression, affects localization, decreases expression, decreases phosphorylation (+1 more)	6
Resveratrol	decreases expression, increases expression, decreases reaction, increases activity, decreases phosphorylation (+1 more)	5
sodium arsenite	increases phosphorylation, decreases expression, affects cotreatment, increases abundance, increases expression (+2 more)	4
Curcumin	decreases reaction, increases activity, decreases activity	4
Estradiol	affects expression, decreases reaction, increases phosphorylation, decreases expression, increases expression	4
Tetradecanoylphorbol Acetate	decreases reaction, increases activity, increases phosphorylation, increases reaction, increases expression	4
arsenite	increases activity, affects reaction, increases acetylation, decreases reaction, affects binding (+4 more)	3
Arsenic Trioxide	increases ubiquitination, decreases reaction, increases phosphorylation, decreases expression, increases activity (+1 more)	3
Vorinostat	affects cotreatment, decreases expression, decreases reaction, increases activity, decreases phosphorylation	3
Doxorubicin	decreases expression, increases phosphorylation, increases reaction	3
Valproic Acid	decreases expression, increases expression	3
moringin	affects cotreatment, increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, decreases phosphorylation	2
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases reaction, increases activity, increases phosphorylation, increases expression	2
Bortezomib	increases activity, increases expression	2
Air Pollutants	decreases expression, increases abundance, affects response to substance, increases expression	2
Cannabidiol	affects cotreatment, increases expression, decreases expression	2
Drugs, Chinese Herbal	decreases phosphorylation, increases activity	2
Gallic Acid	decreases reaction, increases phosphorylation, decreases activity	2
Ibuprofen	decreases reaction, increases activity, decreases activity	2
Rotenone	decreases reaction, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects response to substance, increases expression	2
alpinumisoflavone	decreases expression	1
aristolochic acid I	decreases expression	1
gingerenone A	decreases reaction, increases phosphorylation	1
graphene oxide	decreases expression	1
crenigacestat	decreases reaction, increases phosphorylation	1
geldanamycin	increases degradation	1
parthenolide	decreases reaction, increases phosphorylation	1

ChEMBL screening assays

470 unique, capped per target: 461 binding, 8 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1805652	Binding	Inhibition of IKK in human A549 cells assessed as inhibition of TNF-alpha-induced IkappaB phosphorylation preincubated for 30 mins before TNFalpha challenge	Synthesis and identification of new 4-arylidene curcumin analogues as potential anticancer agents targeting nuclear factor-κB signaling pathway. — J Med Chem
CHEMBL3369239	Functional	Inhibition of IKKbeta expression in human THP1 cells at 20 to 100 uM by Western blotting method	Pyrano-isochromanones as IL-6 inhibitors: synthesis, in vitro and in vivo antiarthritic activity. — J Med Chem
CHEMBL4325216	ADMET	Inhibition of human IKKalpha at 1 uM relative to control	Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8DR	Abcam HCT 116 CHUK KO	Cancer cell line	Male
CVCL_B8U6	Abcam MCF-7 CHUK KO	Cancer cell line	Female
CVCL_B9FZ	Abcam A-549 CHUK KO	Cancer cell line	Male
CVCL_D7MI	Ubigene A-549 CHUK KO	Cancer cell line	Male
CVCL_D8J0	Ubigene HCT 116 CHUK KO	Cancer cell line	Male
CVCL_D9C0	Ubigene HEK293 CHUK KO	Transformed cell line	Female
CVCL_E0A6	Ubigene HeLa CHUK KO	Cancer cell line	Female
CVCL_SJ04	HAP1 CHUK (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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