Inhibition of NF-кB

The use of high-throughput screening has revolutionized the drug discovery process. Recently, biotechnology companies focused on assay detection methodologies, automation capabilities, miniaturization of assays and microfluidics have emerged. Many of these companies and their associated technology are geared toward the generation of thousands of data points, across a variety of screening platforms (cell-based, biochemical, receptors), quickly and at minimal cost. Nonetheless, the screening of hundreds of thousands of samples can be an expensive endeavor and much of the work wasted if a well established screening strategy is not in place.

[1]  P. Baeuerle,et al.  NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory molecules. , 1997, Advances in immunology.

[2]  A. Ciechanover,et al.  Inhibition of NF‐κB cellular function via specific targeting of the IκB‐ubiquitin ligase , 1997 .

[3]  A. Ciechanover,et al.  Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Egido,et al.  Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. , 1997, Circulation.

[5]  Matthias Mann,et al.  IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation , 1997 .

[6]  David Baltimore,et al.  NF-κB: Ten Years After , 1996, Cell.

[7]  A. Nordheim,et al.  Signalling pathways: Jack of all cascades , 1996, Current Biology.

[8]  David M. Rothwarf,et al.  A cytokine-responsive IκB kinase that activates the transcription factor NF-κB , 1997, Nature.

[9]  J. van Oirschot,et al.  Dimethylthiourea protects rats against gram-negative sepsis and decreases tumor necrosis factor and nuclear factor kappaB activity. , 1997, The Journal of laboratory and clinical medicine.

[10]  T. Nakajima,et al.  Thrombin Activates NF‐κB through Thrombin Receptor and Results in Proliferation of Vascular Smooth Muscle Cells: Role of Thrombin in Atherosclerosis and Restenosis , 1997, Annals of the New York Academy of Sciences.

[11]  H. Asahara,et al.  High DNA-binding activity of transcription factor NF-kappa B in synovial membranes of patients with rheumatoid arthritis. , 1995, Biochemistry and molecular biology international.

[12]  Inder M. Verma,et al.  IκB kinase: Beginning, not the end , 1997 .

[13]  A. Manning.  Transcription factors: a new frontier for drug discovery , 1996 .

[14]  H. Jaeschke,et al.  INHIBITION OF NF‐KB ACTIVATION BY DIMETHYL SULFOXIDE CORRELATES WITH SUPPRESSION OF TNF‐α FORMATION, REDUCED ICAM‐1 GENE TRANSCRIPTION, AND PROTECTION AGAINST ENDOTOXIN‐INDUCED LIVER INJURY , 1997 .

[15]  A. Ben-Baruch,et al.  Signals and Receptors Involved in Recruitment of Inflammatory Cells (*) , 1995, The Journal of Biological Chemistry.

[16]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[17]  A. Israël,et al.  I kappa B epsilon, a novel member of the IκB family, controls RelA and cRel NF‐κB activity , 1997 .

[18]  T. Hunter,et al.  Development of a Nonradioactive, Time-Resolved Fluorescence Assay for the Measurement of Jun N-Terminal Kinase Activity , 1997 .

[19]  Richard Treisman,et al.  Transcriptional Regulation by Extracellular signals: Mechanisms and Specificity , 1995, Cell.

[20]  T. Maniatis,et al.  Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. , 1995, Genes & development.

[21]  D. W. Anderson,et al.  2-Chloro-4-(trifluoromethyl)pyrimidine-5-N-(3′,5′-bis (trifluoromethyl)phenyl)carboxamide: A Potent Inhibitor of NF-ϰB- and AP-1-Mediated Gene Expression Identified Using Solution-Phase Combinatorial Chemistry. , 1998 .

[22]  Mike Rothe,et al.  IκB Kinase-β: NF-κB Activation and Complex Formation with IκB Kinase-α and NIK , 1997 .

[23]  T. Maniatis.  Catalysis by a Multiprotein IκB Kinase Complex , 1997, Science.

[24]  Thomas Henkel,et al.  Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-κB subunit , 1992, Cell.

[25]  D. Goeddel,et al.  Identification and Characterization of an IκB Kinase , 1997, Cell.

[26]  P. Baeuerle,et al.  Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial tissue. , 1996, Arthritis and rheumatism.

[27]  D. W. Anderson,et al.  2-Chloro-4-(trifluoromethyl)pyrimidine-5-N-(3',5'- bis(trifluoromethyl)phenyl)-carboxamide: a potent inhibitor of NF-kappa B- and AP-1-mediated gene expression identified using solution-phase combinatorial chemistry. , 1998, Journal of medicinal chemistry.

[28]  G. Franzoso,et al.  Structure, regulation and function of NF-kappa B. , 1994, Annual review of cell biology.

[29]  R. Knuechel,et al.  Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. , 1996, The Journal of clinical investigation.

[30]  M. Mann,et al.  Identification of the receptor component of the IκBα–ubiquitin ligase , 1998, Nature.

[31]  P. Baeuerle,et al.  Role of nuclear factor‐kappa B in atherogenesis , 1997, Experimental physiology.

[32]  E. Gravallese,et al.  Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65. , 1995, Arthritis and rheumatism.

[33]  E. Zandi,et al.  The IκB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKβ, Necessary for IκB Phosphorylation and NF-κB Activation , 1997, Cell.

[34]  A. Baldwin,et al.  THE NF-κB AND IκB PROTEINS: New Discoveries and Insights , 1996 .

[35]  M. Suto,et al.  Peptide inhibitors of IKB protease: Modification of the C-termini of Z-LLF-CHO , 1996 .

[36]  A. Joly,et al.  N-acetyl-leucinyl-leucinyl-norleucinal inhibits lipopolysaccharide-induced NF-kappaB activation and prevents TNF and IL-6 synthesis in vivo. , 1997, Cellular immunology.

[37]  D. Baltimore,et al.  NF-κB Activation: The IκB Kinase Revealed? , 1997, Cell.