Related ArticlesThe SHAPES strategy: an NMR-based approach for lead generation in drug discovery.
Chem Biol. 1999 Oct;6(10):755-69
Authors: Fejzo J, Lepre CA, Peng JW, Bemis GW, Ajay , Murcko MA, Moore JM
BACKGROUND: Recently, it has been shown that nuclear magnetic resonance (NMR) may be used to identify ligands that bind to low molecular weight protein drug targets. Recognizing the utility of NMR as a very sensitive method for detecting binding, we have focused on developing alternative approaches that are applicable to larger molecular weight drug targets and do not require isotopic labeling. RESULTS: A new method for lead generation (SHAPES) is described that uses NMR to detect binding of a limited but diverse library of small molecules to a potential drug target. The compound scaffolds are derived from shapes most commonly found in known therapeutic agents. NMR detection of low (microM-mM) affinity binding is achieved using either differential line broadening or transferred NOE (nuclear Overhauser effect) NMR techniques. CONCLUSIONS: The SHAPES method for lead generation by NMR is useful for identifying potential lead classes of drugs early in a drug design program, and is easily integrated with other discovery tools such as virtual screening, high-throughput screening and combinatorial chemistry.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Top Curr Chem. 2011 Sep 14;
Authors: Stark JL, Powers R
Abstract
Drug discovery is a complex and costly endeavor, where few drugs that reach the clinical testing phase make it to market. High-throughput screening (HTS) is the primary method used by the pharmaceutical industry to identify initial lead compounds. Unfortunately, HTS has a high failure rate and is not particularly efficient at...
[NMR paper] NMR-based methods and strategies for drug discovery.
NMR-based methods and strategies for drug discovery.
Related Articles NMR-based methods and strategies for drug discovery.
Chem Soc Rev. 2003 Nov;32(6):365-72
Authors: Salvatella X, Giralt E
Nuclear Magnetic Resonance (NMR) spectroscopy has long been a favourite tool of chemists interested in host-guest systems because it permits access to a wealth of information about the molecular recognition reaction. NMR has evolved dramatically in the last 15 years and, in parallel with the development of NMR methods for the determination of protein...
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11-24-2010 09:16 PM
[NMR paper] NMR-based screening methods for lead discovery.
NMR-based screening methods for lead discovery.
Related Articles NMR-based screening methods for lead discovery.
EXS. 2003;(93):183-202
Authors: Vogtherr M, Fiebig K
Diversity and robustness of NMR based screening methods make these techniques highly attractive as tools for drug discovery. Although not all screening techniques discussed here may be applicable to any given target, there is however a good chance that at least one of the described methods will prove productive in finding several medium affinity ligands. A comparison of each of...
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11-24-2010 09:01 PM
[NMR paper] MS/NMR: a structure-based approach for discovering protein ligands and for drug desig
MS/NMR: a structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy.
Related Articles MS/NMR: a structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy.
Anal Chem. 2001 Feb 1;73(3):571-81
Authors: Moy FJ, Haraki K, Mobilio D, Walker G, Powers R, Tabei K, Tong H, Siegel MM
A protocol is described...
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11-19-2010 08:32 PM
NMR Screening and Hit Validation in Fragment Based Drug Discovery.
NMR Screening and Hit Validation in Fragment Based Drug Discovery.
Related Articles NMR Screening and Hit Validation in Fragment Based Drug Discovery.
Curr Top Med Chem. 2010 Sep 2;
Authors: Campos-Olivas R
Over the past three decades nuclear magnetic resonance spectroscopy has been developed into a mature technique for the characterization of interactions of small molecule ligands with their corresponding protein and nucleic acid receptors. In fact, a significant number of industrial and academic laboratories employ NMR for screening small...
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09-03-2010 02:30 PM
[BMNRC community] NMR-based screening: a powerful tool in fragment-based drug discovery
NMR-based screening: a powerful tool in fragment-based drug discovery
http://www.rsc.org/delivery/_ArticleLinking/DisplayHTMLArticleforfree.cfm?JournalCode=AN&Year=2007&ManuscriptID=b709658p&Iss=7
Go to BMNRC community to find more info about this topic.
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09-02-2010 04:59 AM
[NMR paper] NMR-based discovery of lead inhibitors that block DNA binding of the human papillomav
NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein.
J Med Chem. 1997 Sep 26;40(20):3144-50
Authors: Hajduk PJ, Dinges J, Miknis GF, Merlock M, Middleton T, Kempf DJ, Egan DA, Walter KA, Robins TS, Shuker SB, Holzman TF, Fesik SW
The E2 protein is required for the replication of human...
The SHAPES strategy: an NMR-based approach for lead generation in drug discovery.
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