Identification of novel scaffolds for IκB kinase beta inhibitor via a high throughput screening TR-FRET assay

Combinatorial Chemistry and High Throughput Screening

Volumn 13, Issue 9, 2010, Pages 790-797

  Oh, Kwang Seok ^a   Lee, Sunghou ^b   Choi, Joong Kwon ^a   Lee, Byung Ho ^a  

^a Korea Research Institute of Chemical Technology   (South Korea)

^b Sangmyung University   (South Korea)

Author keywords

I B kinase ; IKK inhibitor; Time resolved fluorescence resonance energy transfer

Indexed keywords

1 (THIOPHEN OR FURAN) 2,3 DIHYDROIMIDAZO[1,5]PYRIDINE; 2 PHENYLOXAZOLO[5,4]PYRIDINE; 7 BENZOYL 4 PHENYLCYCLOPENTA[1,2]OXAZINE; I KAPPA B KINASE BETA; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG DETERMINATION; DRUG IDENTIFICATION; DRUG SELECTIVITY; FLUORESCENCE RESONANCE ENERGY TRANSFER; HIGH THROUGHPUT SCREENING; MOLECULAR LIBRARY; PRIORITY JOURNAL;

ENZYME INHIBITORS; FLUORESCENCE RESONANCE ENERGY TRANSFER; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; I-KAPPA B KINASE;

EID: 78349278099     PISSN: 13862073     EISSN: None     Source Type: Journal    
DOI: 10.2174/138620710792927367     Document Type: Article

References (20)

1. Baldwin, A.S. Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu. Rev. Immunol., 1996, 14, 649-683.
2. Barnes, P.J.; Karin, M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med., 1997, 336, 1066-1071.
3. Latimer, M.; Ernst, M.K.; Dunn, L.L.; Drutskaya, M.; Rice, N.R. The N-terminal domain of IkappaB alpha masks the nuclear localization signal(s) of p50 and c-Rel homodimers. Mol. Cell. Biol., 1998, 18, 2640-2649.
4. Matthews, J.R.; Hay, R.T. Regulation of the DNA binding activity of NF-kappa B. Int. J. Biochem. Cell Biol., 1995, 27, 865-879.
5. Hay, R.T.; Vuillard, L.; Desterro, J.M.; Rodriguez, M.S. Control of NF-kappa B transcriptional activation by signal induced proteolysis of I kappa B alpha. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 1999, 354, 1601-1609.
6. Karin, M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex. Oncogene, 1999, 18, 6867-6874.
7. Xiao, G.; Harhaj, E.W.; Sun, S.C. Domain-specific interaction with the I kappa B kinase (IKK) regulatory subunit IKK gamma is an essential step in tax-mediated activation of IKK. J. Biol. Chem., 2000, 275, 34060-34067.
8. Delhase, M.; Hayakawa, M.; Chen, Y.; Karin, M. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science, 1999, 284, 309-313.
9. Hu, Y.; Baud, V.; Delhase, M.; Zhang, P.; Deerinck, T.; Ellisman, M.; Johnson, R.; Karin, M. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase. Science, 1999, 284, 316-320.
10. Sadler, T.M.; Achilleos, M.; Ragunathan, S.; Pitkin, A.; LaRocque, J.; Morin, J.; Annable, R.; Greenberger, L.M.; Frost, P.; Zhang, Y. Development and comparison of two nonradioactive kinase assays for I kappa B kinase. Anal. Biochem., 2004, 326, 106-113.
11. Sharlow, E.R.; Leimgruber, S.; Yellow-Duke, A.; Barrett, R.; Wang, Q.J.; Lazo, J.S. Development, validation and implementation of immobilized metal affinity for phosphochemicals (IMAP)-based high throughput screening assays for low-molecular-weight compound libraries. Nat. Protoc., 2008, 3, 1350-1363.
12. Baxter, A.; Brough, S.; Cooper, A.; Floettmann, E.; Foster, S.; Harding, C.; Kettle, J.; McInally, T.; Martin, C.; Mobbs, M.; Needham, M.; Newham, P.; Paine, S.; St-Gallay, S.; Salter, S.; Unitt, J.; Xue, Y. Hit-to-lead studies: the discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 2817-2822.
13. Kishore, N.; Sommers, C.; Mathialagan, S.; Guzova, J.; Yao, M.; Hauser, S.; Huynh, K.; Bonar, S.; Mielke, C.; Albee, L.; Weier, R.; Graneto, M.; Hanau, C.; Perry, T.; Tripp, C.S. A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J. Biol. Chem., 2003, 278, 32861-32871.
14. Vincenti, M.P.; Brinckerhoff, C.E. The potential of signal transduction inhibitors for the treatment of arthritis: Is it all just JNK? J. Clin. Invest., 2001, 108, 181-183.
15. Medicherla, S.; Ma, J.Y.; Mangadu, R.; Jiang, Y.; Zhao, J.J.; Almirez, R.; Kerr, I.; Stebbins, E.G.; O'Young, G.; Kapoun, A.M.; Luedtke, G.; Chakravarty, S.; Dugar, S.; Genant, H.K.; Protter, A.A. A selective p38 alpha mitogen-activated protein kinase inhibitor reverses cartilage and bone destruction in mice with collagen-induced arthritis. J. Pharmacol. Exp. Ther., 2006, 318, 132-141.
16. Zhang, J.H.; Chung, T.D.; Oldenburg, K.R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen, 1999, 4, 67-73.
17. Wisniewski, D.; LoGrasso, P.; Calaycay, J.; Marcy, A. Assay for IkappaB kinases using an in vivo biotinylated IkappaB protein substrate. Anal. Biochem., 1999, 274, 220-228.
18. Burke, J.R.; Miller, K.R.; Wood, M.K.; Meyers, C.A. The multisubunit IkappaB kinase complex shows random sequential kinetics and is activated by the C-terminal domain of IkappaB alpha. J. Biol. Chem., 1998, 273, 12041-12046.
19. Li, J.; Peet, G.W.; Pullen, S.S.; Schembri-King, J.; Warren, T.C.; Marcu, K.B.; Kehry, M.R.; Barton, R.; Jakes, S. Recombinant IkappaB kinases alpha and beta are direct kinases of Ikappa Balpha. J. Biol. Chem., 1998, 273, 30736-30741.
20. Cho, S.Y.; Baek, J.Y.; Han, S.S.; Kang, S.K.; Ha, J.D.; Ahn, J.H.; Lee, J.D.; Kim, K.R.; Cheon, H.G.; Rhee, S.D.; Yang, S.D.; Yon, G.H.; Pak, C.S.; Choi, J.K. PTP-1B inhibitors: cyclopenta[d][1,2]- oxazine derivatives. Bioorg. Med. Chem. Lett., 2006, 16, 499-502.