Faculty Opinions recommendation of Pseudodynamic combinatorial libraries: a receptor-assisted approach for drug discovery.

2004 ◽  
Author(s):  
Dennis Hall
Keyword(s):  
Drug Discovery ◽  
Combinatorial Libraries

Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries

1994 ◽  
Vol 37 (9) ◽  
pp. 1233-1251 ◽  
Author(s):  
Mark A. Gallop ◽  
Ronald W. Barrett ◽  
William J. Dower ◽  
Stephen P. A. Fodor ◽  
Eric M. Gordon
Keyword(s):  
Drug Discovery ◽  
Combinatorial Libraries

scholarly journals Rational screening of oligonucleotide combinatorial libraries for drug discovery

1993 ◽  
Vol 21 (8) ◽  
pp. 1853-1856 ◽  
Author(s):  
David J. Ecker ◽  
Timothy A. Vickers ◽  
Ronnie Hanecak ◽  
Vickie Diver ◽  
Kevin Anderson
Keyword(s):  
Drug Discovery ◽  
Combinatorial Libraries ◽  
Rational Screening

scholarly journals The Effects of Combinatorial Chemistry and Technologies on Drug Discovery and Biotechnology – a Mini Review

2014 ◽  
Vol 13 (2) ◽  
pp. 87-108 ◽  
Author(s):  
Pierfausto Seneci ◽  
Giorgio Fassina ◽  
Vladimir Frecer ◽  
Stanislav Miertus
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Expert Opinion ◽  
High Throughput ◽  
Combinatorial Chemistry ◽  
Rational Design ◽  
Combinatorial Libraries ◽  
Computer Assisted ◽  
Future Trends ◽  
The Impact

Abstract The review will focus on the aspects of combinatorial chemistry and technologies that are more relevant in the modern pharmaceutical process. An historical, critical introduction is followed by three chapters, dealing with the use of combinatorial chemistry/high throughput synthesis in medicinal chemistry; the rational design of combinatorial libraries using computer-assisted combinatorial drug design; and the use of combinatorial technologies in biotechnology. The impact of “combinatorial thinking” in drug discovery in general, and in the examples reported in details, is critically discussed. Finally, an expert opinion on current and future trends in combinatorial chemistry and combinatorial technologies is provided.

NMR-based screening in drug discovery

1999 ◽  
Vol 32 (3) ◽  
pp. 211-240 ◽  
Author(s):  
Philip J. Hajduk ◽  
Robert P. Meadows ◽  
Stephen W. Fesik
Keyword(s):  
Drug Discovery ◽  
Ligand Binding ◽  
Chemical Shifts ◽  
Combinatorial Libraries ◽  
Screening Methods ◽  
Binding Interaction ◽  
Widespread Application ◽  
Affinity Ligands ◽  
High Affinity ◽  
Technological Advances

1. Introduction 2112. Screening methods 2132.1 Chemical shifts 2132.2 Diffusion 2142.3 Transverse relaxation 2182.4 Nuclear Overhauser effects 2183. Strategies for drug discovery and design 2213.1 Fragment-based methods 2213.1.1 Linked-fragment approach 2213.1.2 Directed combinatorial libraries 2223.1.3 Modification of high-affinity ligands 2233.1.4 Solvent mapping techniques 2233.2 High-throughput NMR-based screening 2243.3 Enzymatic assays 2264. Discovery of novel ligands 2274.1 High-affinity ligands for FKBP 2274.2 Potent inhibitors of stromelysin 2294.3 Ligands for the DNA-binding domain of the E2 protein 2334.4 Discovery of Erm methyltransferase inhibitors 2334.5 Phosphotyrosine mimetics for SH2 domains 2365. Conclusions 2376. References 237A critical step in the drug discovery process is the identification of high-affinity ligands for macromolecular targets. Traditionally, the identification of such lead compounds has been accomplished through the high-throughout screening (HTS) of corporate compound repositories. Conventional HTS methodology has enjoyed widespread application and success in the pharmaceutical industry and, through recent technological advances in screening (Fernandes, 1998; Oldenburg et al. 1998; Silverman et al. 1998) and combinatorial chemistry (Fauchere et al. 1998; Fecik et al. 1998), these programs will continue to have a prominent role in drug discovery. However, suitable leads cannot always be found using conventional methods. This is not surprising since typical corporate libraries contain fewer than 106 compounds compared with the estimated 1050–1080 universe of compounds (Martin, 1997). In addition, most conventional assays are limited to screening libraries of compounds against proteins with known function, excluding the large number of targets becoming available from genomics research.Recently, a number of NMR-based screening methods have been employed to identify and design lead ligands for protein targets (see Table 1). These NMR-based strategies can augment ongoing conventional HTS for identifying leads and can be used to aid in lead optimization. All of these techniques take advantage of the fact that upon complex formation between a target molecule and a ligand, significant perturbations can be observed in NMR-sensitive parameters of either the target or the ligand. These perturbations can be used qualitatively to detect ligand binding or quantitatively to assess the strength of the binding interaction. In addition, some of the techniques allow the identification of the ligand binding site or which part of the ligand is responsible for interacting with the target. In this article, the current state of NMR-based screening is reviewed.

The maturation of DNA encoded libraries: opportunities for new users

2020 ◽  
Author(s):  
Daniel Conole ◽  
James H Hunter ◽  
Michael J Waring
Keyword(s):  
Data Analysis ◽  
Cost Effectiveness ◽  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
New Technology ◽  
Combinatorial Libraries ◽  
Library Design ◽  
First Time ◽  
Screening Technology

DNA-encoded combinatorial libraries (DECLs) represent an exciting new technology for high-throughput screening, significantly increasing its capacity and cost–effectiveness. Historically, DECLs have been the domain of specialized academic groups and industry; however, there has recently been a shift toward more drug discovery academic centers and institutes adopting this technology. Key to this development has been the simplification, characterization and standardization of various DECL subprotocols, such as library design, affinity screening and data analysis of hits. This review examines the feasibility of implementing DECL screening technology as a first-time user, particularly in academia, exploring the some important considerations for this, and outlines some applications of the technology that academia could contribute to the field.

scholarly journals Combinatorial chemistry. Facing the challenge of chemical genomics

2001 ◽  
Vol 73 (9) ◽  
pp. 1487-1498 ◽  
Author(s):  
Ferenc Darvas ◽  
Gyorgy Dorman ◽  
Laszlo Urge ◽  
Istvan Szabo ◽  
Zsolt Ronai ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Combinatorial Chemistry ◽  
High Throughput Screening ◽  
Early Stage ◽  
Combinatorial Libraries ◽  
Specific Marker ◽  
Chemical Genomics ◽  
High Quality ◽  
Sequential Approach ◽  
Gene Map

In the age of high-throughput screening and combinatorial chemistry, the focus of drug discovery is to replace the sequential approach with the most effective parallel approach. By the completion of the human gene-map, understanding and healing a disease require the integration of genomics, proteomics, and, very recently, metabolomics with early utilization of diverse small-molecule libraries to create a more powerful "total" drug discovery approach.In this post-genomic era, there is an enhanced demand for information-enriched combinatorial libraries which are high-quality, chemically and physiologically stable, diverse, and supported by measured and predicted data. Furthermore, specific marker libraries could be used for early functional profiling of the genome, proteome, and metabolome. In this new operating model, called "combinatorial chemical genomics", an optimal combination of the marker and high-quality libraries provides a novel synergy for the drug discovery process at a very early stage.

Drug discovery by dynamic combinatorial libraries

2002 ◽  
Vol 1 (1) ◽  
pp. 26-36 ◽  
Author(s):  
Olof Ramström ◽  
Jean-Marie Lehn
Keyword(s):  
Drug Discovery ◽  
Combinatorial Libraries
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