Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9RDS3H)

DOT Name	Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)
Synonyms	I-kappa-B-kinase beta; IKK-B; IKK-beta; IkBKB; EC 2.7.11.10; I-kappa-B kinase 2; IKK-2; IKK2; Nuclear factor NF-kappa-B inhibitor kinase beta; NFKBIKB; Serine/threonine protein kinase IKBKB; EC 2.7.11.1
Gene Name	IKBKB
Related Disease	Severe combined immunodeficiency due to IKK2 deficiency ( ) Immunodeficiency 15a ( )
UniProt ID	IKKB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3BRT; 3BRV; 4E3C; 4KIK
EC Number	2.7.11.1; 2.7.11.10
Pfam ID	PF18397 ; PF12179 ; PF00069
Sequence	MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCL EIQIMRRLTHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRKYLNQFENCCGLREG AILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEQRLIHKIIDLGYAKELDQGSLCT SFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSE VDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCF KALDDILNLKLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLA LIPDKPATQCISDGKLNEGHTLDMDLVFLFDNSKITYETQISPRPQPESVSCILQEPKRN LAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNSMASMSQQLK AKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMAL QTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQS FEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDEKTVVRLQEKRQKELWNLLKI ACSKVRGPVSGSPDSMNASRLSQPGQLMSQPSTASNSLPEPAKKSEELVAEAHNLCTLLE NAIQDTVREQDQSFTALDWSWLQTEEEEHSCLEQAS
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. Phosphorylates inhibitors of NF-kappa-B on 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus.
Tissue Specificity	Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.
KEGG Pathway	Antifolate resistance (hsa01523 ) MAPK sig.ling pathway (hsa04010 ) Ras sig.ling pathway (hsa04014 ) Chemokine sig.ling pathway (hsa04062 ) NF-kappa B sig.ling pathway (hsa04064 ) FoxO sig.ling pathway (hsa04068 ) mTOR sig.ling pathway (hsa04150 ) PI3K-Akt sig.ling pathway (hsa04151 ) Apoptosis (hsa04210 ) Osteoclast differentiation (hsa04380 ) Toll-like receptor sig.ling pathway (hsa04620 ) NOD-like receptor sig.ling pathway (hsa04621 ) RIG-I-like receptor sig.ling pathway (hsa04622 ) Cytosolic D.-sensing pathway (hsa04623 ) C-type lectin receptor sig.ling pathway (hsa04625 ) IL-17 sig.ling pathway (hsa04657 ) Th1 and Th2 cell differentiation (hsa04658 ) Th17 cell differentiation (hsa04659 ) T cell receptor sig.ling pathway (hsa04660 ) B cell receptor sig.ling pathway (hsa04662 ) TNF sig.ling pathway (hsa04668 ) Neurotrophin sig.ling pathway (hsa04722 ) Insulin sig.ling pathway (hsa04910 ) Adipocytokine sig.ling pathway (hsa04920 ) Type II diabetes mellitus (hsa04930 ) Insulin resistance (hsa04931 ) Non-alcoholic fatty liver disease (hsa04932 ) Alcoholic liver disease (hsa04936 ) Alzheimer disease (hsa05010 ) Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120 ) Pathogenic Escherichia coli infection (hsa05130 ) Shigellosis (hsa05131 ) Salmonella infection (hsa05132 ) Yersinia infection (hsa05135 ) Chagas disease (hsa05142 ) Toxoplasmosis (hsa05145 ) Hepatitis C (hsa05160 ) Hepatitis B (hsa05161 ) Measles (hsa05162 ) Human cytomegalovirus infection (hsa05163 ) Influenza A (hsa05164 ) Human papillomavirus infection (hsa05165 ) Human T-cell leukemia virus 1 infection (hsa05166 ) Kaposi sarcoma-associated herpesvirus infection (hsa05167 ) Herpes simplex virus 1 infection (hsa05168 ) Epstein-Barr virus infection (hsa05169 ) Human immunodeficiency virus 1 infection (hsa05170 ) Coro.virus disease - COVID-19 (hsa05171 ) Pathways in cancer (hsa05200 ) MicroR.s in cancer (hsa05206 ) Chemical carcinogenesis - reactive oxygen species (hsa05208 ) Pancreatic cancer (hsa05212 ) Prostate cancer (hsa05215 ) Chronic myeloid leukemia (hsa05220 ) Acute myeloid leukemia (hsa05221 ) Small cell lung cancer (hsa05222 ) PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 ) Lipid and atherosclerosis (hsa05417 ) Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway	ER-Phagosome pathway (R-HSA-1236974 ) NOD1/2 Signaling Pathway (R-HSA-168638 ) TICAM1, RIP1-mediated IKK complex recruitment (R-HSA-168927 ) RIP-mediated NFkB activation via ZBP1 (R-HSA-1810476 ) Downstream TCR signaling (R-HSA-202424 ) p75NTR recruits signalling complexes (R-HSA-209543 ) NF-kB is activated and signals survival (R-HSA-209560 ) FCERI mediated NF-kB activation (R-HSA-2871837 ) TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989 ) Regulation of TNFR1 signaling (R-HSA-5357905 ) TNFR1-induced NF-kappa-B signaling pathway (R-HSA-5357956 ) IKBKB deficiency causes SCID (R-HSA-5602636 ) IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) (R-HSA-5603027 ) IkBA variant leads to EDA-ID (R-HSA-5603029 ) CLEC7A (Dectin-1) signaling (R-HSA-5607764 ) MAP3K8 (TPL2)-dependent MAPK1/3 activation (R-HSA-5684264 ) Interleukin-1 signaling (R-HSA-9020702 ) TRAF6 mediated NF-kB activation (R-HSA-933542 ) NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 (R-HSA-933543 ) IRAK1 recruits IKK complex (R-HSA-937039 ) IKK complex recruitment mediated by RIP1 (R-HSA-937041 ) SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671 ) IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (R-HSA-975144 ) Regulation of NF-kappa B signaling (R-HSA-9758274 ) PKR-mediated signaling (R-HSA-9833482 ) Activation of NF-kappaB in B cells (R-HSA-1169091 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Severe combined immunodeficiency due to IKK2 deficiency	DISE8W83	Definitive	Autosomal recessive	[1]
Immunodeficiency 15a	DIS8XY0I	Strong	Autosomal dominant	[2]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

31 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[11]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[13]
Aspirin	DM672AH	Approved	Aspirin decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[14]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[11]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[15]
Sulindac	DM2QHZU	Approved	Sulindac decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[16]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[18]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[19]
Sulfasalazine	DMICA9H	Approved	Sulfasalazine decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[20]
Ibrutinib	DMHZCPO	Approved	Ibrutinib decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[21]
Afatinib	DMTKD7Q	Approved	Afatinib decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[22]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[24]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[12]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[25]
Abexinostat	DM91LGU	Phase 3	Abexinostat decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[26]
HKI-272	DM6QOVN	Phase 3	HKI-272 decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[22]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[27]
Pelitinib	DMIW453	Phase 2	Pelitinib decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[32]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[27]
BAY11-7082	DMQNOFA	Investigative	BAY11-7082 decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[36]
ROCAGLAMIDE	DME9VTX	Investigative	ROCAGLAMIDE decreases the expression of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[39]
WEDELOLACTONE	DMHL3YV	Investigative	WEDELOLACTONE decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[40]
TPCA-1	DMA14PR	Investigative	TPCA-1 decreases the activity of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[41]
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⏷ Show the Full List of 31 Drug(s)

12 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[9]
Vinblastine	DM5TVS3	Approved	Vinblastine increases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[17]
Colchicine	DM2POTE	Approved	Colchicine increases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[23]
Resiquimod	DML6XSP	Phase 2	Resiquimod increases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[30]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[33]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[34]
(E)-10-nitrooctadec-9-enoic acid	DMTF7JA	Investigative	(E)-10-nitrooctadec-9-enoic acid increases the alkylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[37]
G15	DMMEC9D	Investigative	G15 decreases the phosphorylation of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[38]
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⏷ Show the Full List of 12 Drug(s)

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide affects the localization of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[12]
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1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
acrolein	DMAMCSR	Investigative	acrolein affects the metabolism of Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB).	[35]
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References

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