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BioAssay: AID 588858

Summary assay for small molecule cystic fibrosis induced NFkb Inhibitors

The inflammatory response in Cystic Fibrosis (CF) is a complex interplay between several factors. It has been suggested that pro-inflammatory cytokines are elevated in the epithelial lining fluid samples of CF patients(1). Conversely, expressions of anti-inflammatory cytokines are reduced(2). 90% of all CF deaths occurs from defective lung function. The activation of NFkB via toll-like receptors following bacterial infection is principally involved in the regulation of lung inflammation in CF(3,4) ..more
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AID: 588858
Data Source: Burnham Center for Chemical Genomics (SBCCG-A768-CF-PAF-Summary-Assay)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2011-12-07
Target
Related Experiments
AIDNameTypeComment
588850uHTS identification of cystic fibrosis induced NFkb Inhibitors in a fluoresence assayScreeningdepositor-specified cross reference: Primary Screen
602141uHTS determination of small molecule cytotoxicity in a fluorescence assay to identify cystic fibrosis induced NFkb InhibitorsScreeningdepositor-specified cross reference
602472Single concentration confirmation of uHTS hits for cystic fibrosis induced NFkb Inhibitors in a fluoresence assayScreeningdepositor-specified cross reference
624343Dose Response confirmation of uHTS small molecule hits for cystic fibrosis induced NFkb Inhibitors in a PAF-induced IL8 counterscreenConfirmatorydepositor-specified cross reference
624344Dose Response confirmation of uHTS small molecule hits for cystic fibrosis induced NFkb Inhibitors in a panel assayConfirmatorydepositor-specified cross reference
624347Dose Response confirmation of uHTS small molecule hits for cystic fibrosis induced NFkb Inhibitors in a TNFa-induced IL8 counterscreenConfirmatorydepositor-specified cross reference
651592SAR analysis of molecule cystic fibrosis induced NFkb Inhibitors in a panel assayConfirmatorydepositor-specified cross reference
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: IR21 NS061743-01
Assay Provider: Rangan Maitra, Ph.D., RTI International University

The inflammatory response in Cystic Fibrosis (CF) is a complex interplay between several factors. It has been suggested that pro-inflammatory cytokines are elevated in the epithelial lining fluid samples of CF patients(1). Conversely, expressions of anti-inflammatory cytokines are reduced(2). 90% of all CF deaths occurs from defective lung function. The activation of NFkB via toll-like receptors following bacterial infection is principally involved in the regulation of lung inflammation in CF(3,4)

This project proposes to develop and optimize small molecule inhibitors of the PAF-induced NFkB pathway and distinguish compounds that are inhibiting via the toll-like receptor NFkB pathway to treat lung inflammation in CF.

REFERENCES
1. Bonfield, T.L., Konstan, M. W. & Berger, M. Altered respiratory epithelial cell cytokine production in cystic fibrosis. J Allergy Clin Immunol 104, 72-8 (1999).
2. Bonfield, T.L et al. Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. Am J Respir Cell Mol Biol 13, 257-61 (1995).
3. Zhang, Z., Louboutin, J.P., Weiner, D.J., Goldberg, J.B. & Wilson, J. M. Human airway epithelial cells sense Pseudomonas aeruginosa infection via recognition of flagellin by toll-like receptor 5. Infect Immunol 73, 7151-60 (2005).
4. Greene, C. M. et al. TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells. J. Immunol 174, 1638-46 (2005).
Protocol
Please see pertinent AIDs: 588850
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Additional Information
Grant Number: IR21 NS061743-01

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