IKKβ inhibitor identification: A multi-filter driven novel scaffold

BMC Bioinformatics

Volumn 11, Issue SUPPL. 7, 2010, Pages

  Nagarajan, Shanthi ^a,b   Choo, Hyunah ^a   Cho, Yong S ^a   Shin, Kye Jung ^a   Oh, Kwang Seok ^c   Lee, Byung H ^c   Pae, Ae N ^a  

^a Korea Institute of Science and Technology   (South Korea)

^b University of Science and Technology (UST)   (South Korea)

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

Author keywords

[No Author keywords available]

Indexed keywords

ANTI-INFLAMMATORY AGENTS; ANTI-INFLAMMATORY DRUGS; COMPUTATIONAL MODEL; NUCLEAR FACTOR KAPPAB; NUCLEAR TRANSCRIPTION FACTORS; PHARMACOPHORE MODELING; RECURSIVE PARTITIONING; SMALL MOLECULE INHIBITOR; 3D-QSAR; DATABASE SIZE; IC50 VALUE; MOLECULAR BASIS; PHARMACOPHORE MODELS; PHARMACOPHORES; REGULATORY DOMAIN; SMALL MOLECULES; STRUCTURE-BASED; VIRTUAL SCREENING;

COMPUTATIONAL CHEMISTRY; DATABASE SYSTEMS; DIAGNOSIS; MOLECULES; PHARMACODYNAMICS; REGRESSION ANALYSIS; TRANSCRIPTION; TRANSCRIPTION FACTORS;

TRANSCRIPTION; BIOINFORMATICS;

I KAPPA B KINASE; PROTEIN KINASE INHIBITOR;

ARTICLE; BIOLOGY; CHEMICAL MODEL; CHEMISTRY; DECISION TREE; DRUG ANTAGONISM; DRUG DEVELOPMENT; DRUG EFFECT; DRUG SCREENING; ENZYME ACTIVATION; IC 50; ISOLATION AND PURIFICATION; METHODOLOGY; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

COMPUTATIONAL BIOLOGY; DECISION TREES; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; ENZYME ACTIVATION; I-KAPPA B KINASE; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; PROTEIN KINASE INHIBITORS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77957903729     PISSN: None     EISSN: 14712105     Source Type: Journal    
DOI: 10.1186/1471-2105-11-S7-S15     Document Type: Article

References (40)

1. Mercurio F, Zhu HY, Murray BW, Shevchenko A, Bennett BL, Li JW, Young DB, Barbosa M, Mann M. IKK-1 and IKK-2: Cytokine-activated I kappa B kinases essential for NF-kappa B activation. Science 1997, 278:860-866. 10.1126/science.278.5339.860, 9346484.
2. Beg AA, Baldwin AS. The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev 1993, 7:2064-2070. 10.1101/gad.7.11.2064, 8224838.
3. Scherer DC, Brockman JA, Chen ZJ, Maniatis T, Ballard DW. Signal-Induced Degradation of I-Kappa-B-Alpha Requires Site-Specific Ubiquitination. Proceedings of the National Academy of Sciences of the United States of America 1995, 92:11259-11263. 10.1073/pnas.92.24.11259, 40611, 7479976.
4. Christopher JA, Avitabile BG, Bamborough P, Champigny AC, Cutler GJ, Dyos SL, Grace KG, Kerns JK, Kitson JD, Mellor GW, et al. The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases. Bioorganic & Medicinal Chemistry Letters 2007, 17:3972-3977. 10.1016/j.bmcl.2007.04.088, 17502144.
5. Strnad J, Burke JR. I kappa B kinase inhibitors for treating autoimmune and inflammatory disorders: potential and challenges. Trends in Pharmacological Sciences 2007, 28:142-148. 10.1016/j.tips.2007.01.005, 17287032.
6. Lawrence T, Bebien M, Liu GY, Nizet V, Karin M. IKK alpha limits macrophage NF-kappa B activation and contributes to the resolution of inflammation. Nature 2005, 434:1138-1143. 10.1038/nature03491, 15858576.
7. Nagarajan S, Ahmed A, Choo H, Cho YS, Oh KS, Lee BH, Shin KJ, Pae AN. 3D QSAR pharmacophore model based on diverse IKKβ inhibitors. Journal of Molecular Modeling 2010, 10.1007/s00894-010-0714-8.
8. Lamanna C, Bellini M, Padova A, Westerberg G, Maccari L. Straightforward recursive partitioning model for discarding insoluble compounds in the drug discovery process. Journal of Medicinal Chemistry 2008, 51:2891-2897. 10.1021/jm701407x, 18419111.
9. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977, 33:159-174. 10.2307/2529310, 843571.
10. Murata T, Shimada M, Kadono H, Sakakibara S, Yoshino T, Masuda T, Shimazaki M, Shintani T, Fuchikami K, Bacon KB, et al. Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 2: Improvement of in vitro activity. Bioorganic & Medicinal Chemistry Letters 2004, 14:4013-4017. 10.1016/j.bmcl.2004.05.040, 15225717.
11. Nagarajan S, Choo H, Cho YS, Oh KS, Lee BH, Shin KJ, Pae AN. IKKβ inhibitors Identification Part II: Ligand and Structure Based Virtual Screening. Bioorganic & Medicinal Chemistry 2010,
12. Zhuravel IAI, Kovalenko AV, Borisov SN, Matusovich AV, Il'ya O, Tkachenko SE, Chernykh VE. Substituted pyrido[4',3':5,6]pyrano[2,3-d]pyrimidines and combinatorial library of these derivatives with antitumor activity. Book Substituted pyrido[4',3':5,6]pyrano[2,3-d]pyrimidines and combinatorial library of these derivatives with antitumor activity. (Editor ed.^eds.) City 2006, 13.
13. Hideshima T, Chauhan D, Richardson P, Mitsiades C, Mitsiades N, Hayashi T, Munshi N, Dang L, Castro A, Palombella V, et al. NF-kappa B as a therapeutic target in multiple myeloma. Journal of Biological Chemistry 2002, 277:16639-16647. 10.1074/jbc.M200360200, 11872748.
14. Baxter A, Brough S, Cooper A, Floettmann E, Foster S, Harding C, Kettle J, McInally T, Martin C, Mobbs M, et al. Hit-to-lead studies: the discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors. Bioorganic & Medicinal Chemistry Letters 2004, 14:2817-2822. 10.1016/j.bmcl.2004.03.058, 15125939.
15. Beaulieu F, Ouellet C, Ruediger EH, Belema M, Qiu YP, Yang XJ, Banville J, Burke JR, Gregor KR, MacMaster JF, et al. Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors. Bioorganic & Medicinal Chemistry Letters 2007, 17:1233-1237. 10.1016/j.bmcl.2006.12.017, 17197177.
16. Morwick T, Berry A, Brickwood J, Cardozo M, Catron K, DeTuri M, Emeigh J, Homon C, Hrapchak M, Jacober S, et al. Evolution of the thienopyridine class of inhibitors of I kappa B kinase-beta: Part I: Hit-to-lead strategies. Journal of Medicinal Chemistry 2006, 49:2898-2908. 10.1021/jm0510979, 16686533.
17. Sugiyama H, Yoshida M, Mori K, Kawamoto T, Sogabe S, Takagi T, Oki H, Tanaka T, Kimura H, Ikeura Y. Synthesis and structure activity relationship studies of benzothieno[3,2-b]furan derivatives as a novel class of IKK beta inhibitors. Chemical & Pharmaceutical Bulletin 2007, 55:613-624. 10.1248/cpb.55.613, 17409557.
18. De'ath G, Fabricius KE. Classification and regression trees: A powerful yet simple technique for ecological data analysis. Ecology 2000, 81:3178-3192.
19. Farmen MWL, Rusinko C, Young AR, Stanley S. Statistical deconvoluting of mixtures. Book Statistical deconvoluting of mixtures. (Editor ed.^eds.), City 2002, 6434542.
20. Huang LT, Gromiha MM, Ho SY. iPTREE-STAB: interpretable decision tree based method for predicting protein stability changes upon mutations. Bioinformatics 2007, 23:1292-1293. 10.1093/bioinformatics/btm100, 17379687.
21. Houseman EA, Christensen BC, Yeh RF, Marsit CJ, Karagas MR, Wrensch M, Nelson HH, Wiemels J, Zheng S, Wiencke JK, Kelsey KT. Model-based clustering of DNA methylation array data: a recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions. Bmc Bioinformatics 2008, 9. 10.1186/1471-2105-9-365, 2553421, 18782434.
22. Chohan KK, Paine SW, Mistry J, Barton P, Davis AM. A rapid computational filter for cytochrome P450 1A2 inhibition potential of compound libraries. Journal of Medicinal Chemistry 2005, 48:5154-5161. 10.1021/jm048959a, 16078835.
23. Burton J, Ijjaali I, Barberan O, Petitet F, Vercauteren DP, Michel A. Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2 inhibition: Importance of the quality of the dataset. Journal of Medicinal Chemistry 2006, 49:6231-6240. 10.1021/jm060267u, 17034129.
24. Crius2 (version 410), Accelrys, Inc, San Diego, CA, USA 2005, Crius2.
25. Murata T, Shimada M, Sakakibara S, Yoshino T, Masuda T, Shintani T, Sato H, Koriyama Y, Fukushima K, Nunami N, et al. Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 3: Orally active anti-inflammatory agents. Bioorganic & Medicinal Chemistry Letters 2004, 14:4019-4022. 10.1016/j.bmcl.2004.05.041, 15225718.
26. Bingham AH, Davenport RJ, Gowers L, Knight RL, Lowe C, Owen DA, Parry DM, Pitt WR. A novel series of potent and selective IKK2 inhibitors. Bioorganic & Medicinal Chemistry Letters 2004, 14:409-412. 10.1016/j.bmcl.2003.10.047, 14698170.
27. Bonafoux D, Bonar S, Christine L, Clare M, Donnelly A, Guzova J, Kishore N, Lennon P, Libby A, Mathialagan S, et al. Inhibition of IKK-2 by 2-[(aminocarbonyl)amino]-5-acetylenyl-3-thiophenecarboxamides. Bioorganic & Medicinal Chemistry Letters 2005, 15:2870-2875. 10.1016/j.bmcl.2005.03.090, 15911271.
28. Waelchli R, Bollbuck B, Bruns C, Buhl T, Eder J, Felfel R, Hersperger R, Janser P, Revesz L, Zerwes HG, Schlapbach A. Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK. Bioorganic & Medicinal Chemistry Letters 2006, 16:108-112. 10.1016/j.bmcl.2005.09.035, 16236504.
29. Castro AC, Dang LC, Soucy F, Grenier L, Mazdiyasni H, Hottelet M, Parent L, Pien C, Palombella V, Adams J. Novel IKK inhibitors: beta-carbolines. Bioorganic & Medicinal Chemistry Letters 2003, 13:2419-2422. 10.1016/S0960-894X(03)00408-6, 12824047.
30. Belema M, Bunker A, Nguyen VN, Beaulieu F, Ouellet C, Qu YP, Zhang YH, Martel A, Burke JR, Mclntyre KW, et al. Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2-e)pyrazines as IKK-beta inhibitors. Bioorganic & Medicinal Chemistry Letters 2007, 17:4284-4289. 10.1016/j.bmcl.2007.05.031, 17540562.
31. Tripos Inc. SL, MO 63144, USA
32. Hindle SA, Rarey M, Buning C, Lengauer T. Flexible docking under pharmacophore type constraints. Journal of Computer-Aided Molecular Design 2002, 16:129-149. 10.1023/A:1016399411208, 12188022.
33. Polgar T, Keseru GM. Virtual screening for beta-secretase (BACE1) inhibitors reveals the importance of protonation states at Asp32 and Asp228. Journal of Medicinal Chemistry 2005, 48:3749-3755. 10.1021/jm049133b, 15916426.
34. Polgar T, Magyar C, Simon I, Keseru GM. Impact of ligand protonation on virtual screening against ss-secretase (BACEI). Journal of Chemical Information and Modeling 2007, 47:2366-2373. 10.1021/ci700223p, 17944457.
35. Polgar T, Baki A, Szendrei GI, Keseru GM. Comparative virtual and experimental high-throughput screening for glycogen synthase kinase-3 beta inhibitors. Journal of Medicinal Chemistry 2005, 48:7946-7959. 10.1021/jm050504d, 16335919.
36. Virag I, Polgar T, Keseru GM. Functional virtual screening of estrogen receptor alpha modulators by FlexX-Pharm. Journal of Molecular Structure-Theochem 2005, 725:239-242.
37. Aronov AM, McClain B, Moody CS, Murcko MA. Kinase-likeness and kinase-privileged fragments: Toward virtual polypharmacology. Journal of Medicinal Chemistry 2008, 51:1214-1222. 10.1021/jm701021b, 18288794.
38. Ghose AK, Herbertz T, Pippin DA, Salvino JM, Mallamo JP. Knowledge based prediction of ligand binding modes and rational inhibitor design for kinase drug discovery. Journal of Medicinal Chemistry 2008, 51:5149-5171. 10.1021/jm800475y, 18710211.
39. Liao JJL. Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. Journal of Medicinal Chemistry 2007, 50:409-424. 10.1021/jm0608107, 17266192.
40. Nagarajan S, Doddareddy MR, Choo H, Cho YS, Oh KS, Lee BH, Pae AN. IKK beta inhibitors identification part I: Homology model assisted structure based virtual screening. Bioorganic & Medicinal Chemistry 2009, 17:2759-2766. 10.1016/j.bmc.2009.02.041, 19285872.