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Target has curated data in GtoImmuPdb
Target id: 2074
Nomenclature: mitogen-activated protein kinase kinase kinase 14
Abbreviated Name: NIK
Family: STE-unique family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 947 | 17q21.31 | MAP3K14 | mitogen-activated protein kinase kinase kinase 14 | |
Mouse | - | 942 | 11 66.8 cM | Map3k14 | mitogen-activated protein kinase kinase kinase 14 | |
Rat | - | 942 | 10 q32.1 | Map3k14 | mitogen-activated protein kinase kinase kinase 14 |
Previous and Unofficial Names |
NF-κB-inducing kinase | NIK |
Database Links | |
Alphafold | Q99558 (Hs), Q9WUL6 (Mm) |
BRENDA | 2.7.11.25 |
ChEMBL Target | CHEMBL5888 (Hs), CHEMBL4523500 (Mm) |
Ensembl Gene | ENSG00000006062 (Hs), ENSMUSG00000020941 (Mm), ENSRNOG00000003278 (Rn) |
Entrez Gene | 9020 (Hs), 53859 (Mm), 360640 (Rn) |
Human Protein Atlas | ENSG00000006062 (Hs) |
KEGG Enzyme | 2.7.11.25 |
KEGG Gene | hsa:9020 (Hs), mmu:53859 (Mm), rno:360640 (Rn) |
OMIM | 604655 (Hs) |
Pharos | Q99558 (Hs) |
RefSeq Nucleotide | NM_003954 (Hs), NM_016896 (Mm), NM_001108301 (Rn) |
RefSeq Protein | NP_003945 (Hs), NP_058592 (Mm), NP_001101771 (Rn) |
SynPHARM | 81639 (in complex with compound 31 [PMID: 23374866]) |
UniProtKB | Q99558 (Hs), Q9WUL6 (Mm) |
Wikipedia | MAP3K14 (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific inhibitor tables |
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service. A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: ...2 |
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Target used in screen: nd/NIK(MAP3K14) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
NIK is a kinase that operates downstream of several TNF family receptors, including BAFF (TNFRSF13C), TWEAK (TNFRSF12A), CD40 (TNFRSF5), and OX40 (TNFRSF4), and which mediates non-canonical NF-κB signaling. BAFF, TWEAK, CD40, and OX40 are implicated in the pathogenesis of inflammatory diseases including systemic lupus erythematosus (SLE) [3]. NIK is also an anti-cancer drug target [7]. |
Immuno Process Associations | ||
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General Comments |
Selective inhibition of NIK as a mechanism to disrupt the non-canonical NF-κB pathway is being investigated as a potential oncology intervention [1,7]. |
1. Al-Khawaldeh I, Al Yasiri MJ, Aldred GG, Basmadjian C, Bordoni C, Harnor SJ, Heptinstall AB, Hobson SJ, Jennings CE, Khalifa S et al.. (2021) An Alkynylpyrimidine-Based Covalent Inhibitor That Targets a Unique Cysteine in NF-κB-Inducing Kinase. J Med Chem, 64 (14): 10001-10018. [PMID:34212719]
2. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
3. Brightbill HD, Suto E, Blaquiere N, Ramamoorthi N, Sujatha-Bhaskar S, Gogol EB, Castanedo GM, Jackson BT, Kwon YC, Haller S et al.. (2018) NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus. Nat Commun, 9 (1): 179. [PMID:29330524]
4. Chen G, Cushing TD, Fisher B, He X, Li K, Li Z, Mcgee L, Pattaropong V, Faulder P, Seganish JL et al.. (2009) Alkynyl alcohols as kinase inhibitors. Patent number: WO2009158011A1. Assignee: Amgen Inc.. Priority date: 26/06/2008. Publication date: 30/12/2009.
5. de Leon-Boenig G, Bowman KK, Feng JA, Crawford T, Everett C, Franke Y, Oh A, Stanley M, Staben ST, Starovasnik MA et al.. (2012) The crystal structure of the catalytic domain of the NF-κB inducing kinase reveals a narrow but flexible active site. Structure, 20 (10): 1704-14. [PMID:22921830]
6. Li K, McGee LR, Fisher B, Sudom A, Liu J, Rubenstein SM, Anwer MK, Cushing TD, Shin Y, Ayres M et al.. (2013) Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures. Bioorg Med Chem Lett, 23 (5): 1238-44. [PMID:23374866]
7. Pippione AC, Sainas S, Federico A, Lupino E, Piccinini M, Kubbutat M, Contreras JM, Morice C, Barge A, Ducime A et al.. (2018) N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK. Medchemcomm, 9 (6): 963-968. DOI: 10.1039/C8MD00068A [PMID:30108985]
8. Zhu Y, Ma Y, Zu W, Song J, Wang H, Zhong Y, Li H, Zhang Y, Gao Q, Kong B et al.. (2020) Identification of N-Phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine Derivatives as Novel, Potent, and Selective NF-κB Inducing Kinase (NIK) Inhibitors for the Treatment of Psoriasis. J Med Chem, 63 (13): 6748-6773. [PMID:32479083]
STE-unique family: mitogen-activated protein kinase kinase kinase 14. Last modified on 20/09/2022. Accessed on 13/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2074.