Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets
Abstract
:1. Introduction and Background
1.1. Nuclear Factor Kappa-B (NF-κB) Proteins
1.2. Activation of the Non-Canonical NF-κB Pathway
1.3. Major Components of The Receptor Activated Non-Canonical NF-κB Pathway
1.4. IKKα-Dependent, NF-κB-Independent Signalling Integrates with IKKα-Dependent Non-Canonical NF-κB Signalling to Contribute to Global Cellular Transcription
1.5. Signalling Complexities
2. IKKα in Solid Tumours
IKKα Signalling Independent of NF-κB Pathways in Solid Tumours
3. IKKα Association with Hallmarks of Cancer in Human Tumours
4. NF-κB in Haematological Malignancies
5. Targeting the IKKα and NIK Protein Kinases with Small Molecule Inhibitors
5.1. Development of Small Molecule Inhibitors of IKKα and NIK
5.2. Structure of IKKα and IKKβ from a Small Molecule Design Perspective
5.3. IKKα/β Non-Selective Inhibitors
6. Future Perspectives
Funding
Acknowledgments
Conflicts of Interest
Appendix A
List of chemical names for compounds 1–19 | |
1 | (R)-4-(1-(2-amino-5-chloropyrimidin-4-yl)indolin-6-yl)-2-(thiazol-2-yl)but-3-yn-2-ol |
2 | (R)-10-(3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-N3-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2,3-dicarboxamide |
3 | (R)-6-(3-((3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)phenyl)-4-methoxypicolinamide |
4 | 1-(3-(8-methyl-5-(methylamino)imidazo[1,2-a]thieno[3,2-e]pyrazin-2-yl)phenethyl)urea |
5 | N-((8-methyl-5-(methylamino)imidazo[1,2-a]thieno[3,2-e]pyrazin-2-yl)methyl)aminosulfonamide |
6 | N-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine |
7 | 2-amino-5-(pyridin-4-yl)-4’-sulfamoyl-[1,1’-biphenyl]-3-carboxamide |
8 | N-(2-aminoethyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide |
9 | N-(azetidin-3-yl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide |
10 | N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide |
11 | 4-((4-(benzo[b]thiophen-2-yl)pyrimidin-2-yl)amino)benzoic acid |
12 | 4-((4-(benzo[b]thiophen-2-yl)pyrimidin-2-yl)amino)phenyl)(4-(pyrrolidin-1-yl)piperidin-1-yl)methanone |
13 | 4-((4-(5-(3-amino-3-methylbutyl)thiophen-2-yl)pyrimidin-2-yl)amino)phenyl)(4-(pyrrolidin-1-yl)piperidin-1-yl)methanone |
14 | (1R,2S,3R,4S)-4-(6-amino-9H-purin-9-yl)cyclopentane-1,2,3-triol (NAM) |
15 | 4-(3-cyano-1H-pyrrolo[2,3-b]pyridin-5-yl)benzenesulfonamide |
16 | 5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine |
17 | 5-(1H-pyrazolo[3,4-b]pyridin-4-yl)-1H-indazol-3-amine |
18 | 5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (apigenin) |
19 | 4-(2-amino-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamide (SU909) |
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Paul, A.; Edwards, J.; Pepper, C.; Mackay, S. Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets. Cells 2018, 7, 176. https://doi.org/10.3390/cells7100176
Paul A, Edwards J, Pepper C, Mackay S. Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets. Cells. 2018; 7(10):176. https://doi.org/10.3390/cells7100176
Chicago/Turabian StylePaul, Andrew, Joanne Edwards, Christopher Pepper, and Simon Mackay. 2018. "Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets" Cells 7, no. 10: 176. https://doi.org/10.3390/cells7100176