Proteins > Inhibitor of nuclear factor kappa-B kinase subunit alpha
Page last updated: 2024-08-07 15:22:58
Inhibitor of nuclear factor kappa-B kinase subunit alpha
An inhibitor of nuclear factor kappa-B kinase subunit alpha that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15111]
Synonyms
I-kappa-B kinase alpha;
IKK-A;
IKK-alpha;
IkBKA;
IkappaB kinase;
EC 2.7.11.10;
Conserved helix-loop-helix ubiquitous kinase;
I-kappa-B kinase 1;
IKK1;
Nuclear factor NF-kappa-B inhibitor kinase alpha;
NFKBIKA;
Research
Bioassay Publications (26)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 16 (61.54) | 29.6817 |
| 2010's | 9 (34.62) | 24.3611 |
| 2020's | 1 (3.85) | 2.80 |
Compounds (84)
Drugs with Inhibition Measurements
Drugs with Activation Measurements
Beyond direct Nrf2 activation; reinvestigating 1,2,4-oxadiazole scaffold as a master key unlocking the antioxidant cellular machinery for cancer therapy.European journal of medicinal chemistry, , Aug-05, Volume: 220, 2021
ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.European journal of medicinal chemistry, , Jan-01, Volume: 161, 2019
Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors.Bioorganic & medicinal chemistry, , 05-01, Volume: 26, Issue:8, 2018
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
Structure-based design and biological profile of (E)-N-(4-Nitrobenzylidene)-2-naphthohydrazide, a novel small molecule inhibitor of IκB kinase-β.European journal of medicinal chemistry, , Volume: 46, Issue:4, 2011
From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells.Journal of medicinal chemistry, , Apr-09, Volume: 52, Issue:7, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.Journal of medicinal chemistry, , Dec-30, Volume: 47, Issue:27, 2004
Beyond direct Nrf2 activation; reinvestigating 1,2,4-oxadiazole scaffold as a master key unlocking the antioxidant cellular machinery for cancer therapy.European journal of medicinal chemistry, , Aug-05, Volume: 220, 2021
4-Hydroxy-MedChemComm, , Sep-01, Volume: 8, Issue:9, 2017
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: synthesis, SAR, PK/PD and activity in a preclinical model of rheumatoid arthritis.Bioorganic & medicinal chemistry letters, , Jan-01, Volume: 21, Issue:1, 2011
Novel tricyclic inhibitors of IkappaB kinase.Journal of medicinal chemistry, , Apr-09, Volume: 52, Issue:7, 2009
Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2-e)pyrazines as IKK-beta inhibitors.Bioorganic & medicinal chemistry letters, , Aug-01, Volume: 17, Issue:15, 2007
Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors.Bioorganic & medicinal chemistry letters, , Mar-01, Volume: 17, Issue:5, 2007
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
4-Hydroxy-MedChemComm, , Sep-01, Volume: 8, Issue:9, 2017
Novel IKK inhibitors: beta-carbolines.Bioorganic & medicinal chemistry letters, , Jul-21, Volume: 13, Issue:14, 2003
The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases.Bioorganic & medicinal chemistry letters, , Jul-15, Volume: 17, Issue:14, 2007
5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase.Bioorganic & medicinal chemistry letters, , Dec-15, Volume: 16, Issue:24, 2006
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Enables
This protein enables 10 target(s):
| Target | Category | Definition |
|---|
| protein kinase activity | molecular function | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. [PMID:25399640] |
| protein serine/threonine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. [GOC:bf, MetaCyc:PROTEIN-KINASE-RXN, PMID:2956925] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| ATP binding | molecular function | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. [ISBN:0198506732] |
| IkappaB kinase activity | molecular function | Catalysis of the reaction: ATP + IkappaB protein = ADP + IkappaB phosphoprotein. [EC:2.7.11.10] |
| protein homodimerization activity | molecular function | Binding to an identical protein to form a homodimer. [GOC:jl] |
| protein-containing complex binding | molecular function | Binding to a macromolecular complex. [GOC:jl] |
| protein heterodimerization activity | molecular function | Binding to a nonidentical protein to form a heterodimer. [GOC:ai] |
| scaffold protein binding | molecular function | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. [GOC:BHF, GOC:sjp, PMID:10433269, Wikipedia:Scaffold_protein] |
| transferrin receptor binding | molecular function | Binding to a transferrin receptor. [GOC:pm, PMID:9819414] |
Located In
This protein is located in 4 target(s):
| Target | Category | Definition |
|---|
| nucleoplasm | cellular component | That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653] |
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
| cytoplasmic side of plasma membrane | cellular component | The leaflet the plasma membrane that faces the cytoplasm and any proteins embedded or anchored in it or attached to its surface. [GOC:dos, GOC:tb] |
Active In
This protein is active in 1 target(s):
| Target | Category | Definition |
|---|
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
Part Of
This protein is part of 2 target(s):
| Target | Category | Definition |
|---|
| IkappaB kinase complex | cellular component | A trimeric protein complex that phosphorylates inhibitory-kappaB (I-kappaB) proteins. The complex is composed of two kinase subunits (alpha and beta) and a regulatory gamma subunit (also called NEMO). In a resting state, NF-kappaB dimers are bound to inhibitory IKB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. [GOC:bf, GOC:ma, PMID:12055104, PMID:20300203] |
| CD40 receptor complex | cellular component | A protein complex that contains at least CD40 (a cell surface receptor of the tumour necrosis factor receptor (TNFR) superfamily), and other signaling molecules. [GOC:BHF, PMID:20614026, PMID:9221764] |
Involved In
This protein is involved in 32 target(s):
| Target | Category | Definition |
|---|
| skeletal muscle contraction | biological process | A process in which force is generated within skeletal muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. In the skeletal muscle, the muscle contraction takes advantage of an ordered sarcomeric structure and in most cases it is under voluntary control. [GOC:mtg_cardio, GOC:mtg_muscle] |
| protein phosphorylation | biological process | The process of introducing a phosphate group on to a protein. [GOC:hb] |
| inflammatory response | biological process | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. [GO_REF:0000022, ISBN:0198506732] |
| immune response | biological process | Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. [GO_REF:0000022, GOC:add] |
| canonical NF-kappaB signal transduction | biological process | An intracellular signaling cassette characterized by the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB, also known as the canonical NF-kappaB signaling cascade. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. The canonical NF-kappaB pathway is mainly stimulated by proinflammatory cytokines such as IL-1beta, tumor necrosis factor (TNF)-alpha, antigen ligands, and toll-like receptors (TLRs). [GOC:bf, PMID:12773372, PMID:34659217] |
| I-kappaB phosphorylation | biological process | The process of introducing a phosphate group into an inhibitor of kappa B (I-kappaB) protein. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing bound NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. [GOC:bf, GOC:jl, PMID:21772278, PMID:7594468] |
| Rho protein signal transduction | biological process | An intracellular signaling cassette in which a small monomeric GTPase of the Rho subfamily relays a signal. [GOC:bf] |
| response to xenobiotic stimulus | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. [GOC:jl, GOC:krc] |
| response to virus | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus. [GOC:hb] |
| response to toxic substance | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus. [GOC:lr] |
| anatomical structure morphogenesis | biological process | The process in which anatomical structures are generated and organized. Morphogenesis pertains to the creation of form. [GOC:go_curators, ISBN:0521436125] |
| response to acetate | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an acetate stimulus. [GOC:sm] |
| negative regulation of NF-kappaB transcription factor activity | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of the activity of the transcription factor NF-kappaB. [GOC:dph, GOC:rl, GOC:tb] |
| response to lipopolysaccharide | biological process | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. [GOC:add, ISBN:0721601464] |
| positive regulation of interferon-alpha production | biological process | Any process that activates or increases the frequency, rate, or extent of interferon-alpha production. [GOC:mah, PMID:15546383] |
| response to hydroperoxide | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydroperoxide stimulus. Hydroperoxides are monosubstitution products of hydrogen peroxide, HOOH. [GOC:mah] |
| tumor necrosis factor-mediated signaling pathway | biological process | The series of molecular signals initiated by tumor necrosis factor binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:mah, GOC:signaling] |
| toll-like receptor 4 signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to toll-like receptor 4. [GOC:add, PMID:16551253, PMID:17328678] |
| cellular response to reactive oxygen species | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals. [GOC:mah] |
| non-canonical NF-kappaB signal transduction | biological process | An intracellular signaling cassette characterized by the NIK-dependent processing and activation of NF-kappaB. Begins with activation of the NF-kappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-kappa B2 protein (p100) leading to p100 processing and release of an active NF-kappaB (p52). The non-canonical NF-kappaB signaling pathway is generally activated by ligands of the TNF receptor superfamily, including lymphotoxin beta (LTB), CD40, OX40, RANK, TWEAK and B cell-activating factor (BAFF). [GOC:bf, GOC:mg2, GOC:signaling, GOC:vs, PMID:11239468, PMID:15140882, PMID:34659217] |
| positive regulation of canonical NF-kappaB signal transduction | biological process | Any process that activates or increases the frequency, rate or extent of a canonical NF-kappaB signaling cascade. [GOC:jl] |
| response to amino acid | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amino acid stimulus. An amino acid is a carboxylic acids containing one or more amino groups. [GOC:ef, GOC:mlg] |
| innate immune response | biological process | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. [GO_REF:0000022, GOC:add, GOC:ebc, GOC:mtg_sensu] |
| positive regulation of DNA-templated transcription | biological process | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. [GOC:go_curators, GOC:txnOH] |
| positive regulation of transcription by RNA polymerase II | biological process | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. [GOC:go_curators, GOC:txnOH] |
| positive regulation of NF-kappaB transcription factor activity | biological process | Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB. [GOC:dph, GOC:tb, PMID:15087454, PMID:15170030] |
| striated muscle cell differentiation | biological process | The process in which a relatively unspecialized cell acquires specialized features of a striated muscle cell; striated muscle fibers are divided by transverse bands into striations, and cardiac and voluntary muscle are types of striated muscle. [CL:0000737, GOC:ai] |
| response to cholecystokinin | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cholecystokinin stimulus. [PMID:14622258] |
| cellular response to cadmium ion | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cadmium (Cd) ion stimulus. [GOC:mah] |
| cellular response to tumor necrosis factor | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus. [GOC:mah] |
| cellular response to virus | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus. [GOC:dos] |
| peptidyl-serine phosphorylation | biological process | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. [RESID:AA0037] |