DRUG DISCOVERY AND COMPOUND LIBRARIES

by Selleckchem | Sep 29 2012

INTRODUCTION:
A large number of compounds stored for the purpose of discovering something beneficial and more efficient we are looking for is known as compound library screening. A compound library is constructed for the purpose of drug discovery and is screened for the best drug by high through put screening techniques of recent era. Compounds included in the library are fully organized by a specific database system containing information about the compounds and their related properties like purity, chemical structure, physical, chemical and pharmacological properties, and the preparation of that compound [1]. Lots of libraries of different compounds are available commercially that contain different common or unique type of biochemical compounds. Description of these compounds and complete information is available in a file named research chemical library which can be bought from the suppliers of relevant compound libraries. The compound libraries are screened by using assays for high throughput screening where the drug target is taken as a screening agent and is used against all the compounds specified for that target in the compound library. The possibility of getting the most efficient compound by compound screening library increases with the number of compounds included.

PREPARATION OF COMPOUND LIBRARY:
Compound libraries may be constructed without any specific purpose or they may be for some specific purpose like discovering a specific kinase inhibitor for cancer therapy. If it is specific than compound libraries may also be called research chemicals library should be generated by making some small libraries. For example in case of cancer research and drug discovery, we are interested in the inhibitors of ATP binding sites on the kinase enzyme. For this purpose, rather than screening a whole library of compounds a library would be constructed that would have compounds containing binding sites for ATP binding site on the enzyme. Screening this small specific library would be much easier, more result oriented and less time and money consuming. A library of designed molecules contains the compounds having some modifications in them in order to see the effect of modifications that would prove extremely beneficial if some positive effect is observed after modifying those compounds. Introducing alterations in the compound my be done for altering some of its undesirable for example making it less toxic and more specific to the target cells. Alterations may be done by substituting the side chains some other functional groups or some changes in the compounds’ backbones. Suppliers of the compound library may supply different combinations of compounds in the library.

SCREENING OF COMPOUND LIBRARY:
Screening of compound libraries is a very time consuming and effort demanding task. Libraries can be screened using assays of chemical library screening or high throughput screening. For the purpose of screening a large number of compounds in the library are divided into smaller subgroups and then are screened for a disease of interest. First successful hit on the compound then encourages the researchers to screen for the compound’s function and activity [2]. After successful passage through small molecule inhibitors screening the compound is registered and subjected to further analysis for efficacy in different conditions against the target compound [3]. Other compounds that are related to that chosen initially are also analyzed in order to check if they are also efficient enough to be used as a competitor. Some derivatives of the initially chosen compounds are also made after some changes and looked for efficacy. The derived compounds may be similar to the basic structure of the originally discovered compound but may be more efficacious. Proper storage and full utilization of the compounds chosen from the library for analysis is very important in order to utilize them fully. Recent advances have made it possible to store and manage compounds in the library properly and systematically [4].

REFERENCES:
1. Schneider P, e.a., Self-Organizing Maps in Drug Discovery: Compound Library Design, Scaffold-Hopping, Repurposing Current Medicinal Chemistry, 2009.
2. Su GH, e.a., A Novel Histone Deacetylase Inhibitor Identified by High-Throughput Transcriptional Screening of a Compound Library. Cancer Res, 2000.
3. Huggins DJ, e.a., Rational Methods for the Selection of Diverse Screening Compounds. ACS Chem. Biol., 2011.
4. Gaillard Y, e.a., Use of high-performance liquid chromatography with photodiode-array UV detection for the creation of a 600-compound library application to forensic toxicology. Journal of Chromatography A, 1997.