Introduction: The concept

With the advent of the computer age a different style of thinking came into play. Technology changed the way in which scientists approached things but did not alter the rationale behind the objective. In the medical field the pressure to discover new medical treatments became a financial one rather than a humanitarian one. Pharmaceutical companies made and lost huge sums of money speculating on the potential use of a molecule for clinical purposes. To regulate all of this the USA formed the “federal drug administration” or FDA, while Europe developed the EMA. Strict rules and codes of conducted made the release of new pharmaceuticals more difficult but gave the public a greater sense of security. Pharmaceutical companies found that discovering new molecules under these rules to be an expensive proposition compared to the profits they received from the marketing the drug. Hence the competition to get a drug to the market first and claim a “lions share” of the potential profits has become the guiding rule behind drug development. Every aspect of the discovery process has been streamline to the minimize costs and every labor saving device employed to decrease expenses and increase profits. The initial stage of drug developed is the selection of a molecule or a series of molecules with biological activity [1]. Compound libraries were developed to provide the researcher with a starting and consisted of a series of structural related molecules that could be used in biological assays to determine activities against individual viruses, bacteria or receptors proteins. However, this still required the molecular synthesis of each component and rationale for the molecular structure was very important in the chemical library design, if this was wrong then no biological activity would be found hence wasted resources and time [2]. To combat this uncertainty several different approaches have been developed in designing a compound library [3].

Compound libraries: Solving the design uncertainty

To design a library relevant to the desired objective there are two basic methodologies available. The first is to generate a molecular series and determine biological activity one at a time against a target mechanism [4]. The second method is similar but here a single or series of molecules are screened against a whole panel of different targets such as protein receptor, kinases or transport mechanism [5]. For a compound library screening of individual molecular series each molecule has to be synthesized, purified and characterized. This is an expensive process involving significant facilities and personnel investments. Hence pharmaceutical companies tend not to generate their own random molecule libraries, but small developmental companies have taken on this task and market these libraries to the bigger research companies. In this way the cost of development is recouped and profits generated. The larger developmental companies then hold tens of differently sourced libraries in their arsenal for which the larger pharmaceutical company can screen targets against, again recouping investment and generating profits. Choosing the correct libraries to create and hold is part of the risk to profit margin for these companies.

The second methodology is slightly different; here molecules tend to be gleaned from natural sources of known medicinal properties [6]. These molecules or even extracted fractions can then be tested against potential targets; which creates a need for compound libraries of biological targets [7]

Compound libraries: Screening strategies

The first methodology could reveal sensitivity of one or two molecules against a target mechanism, while the remaining molecules demonstrate no response. This can mean either the responding molecules are investigated for clinical application or if activity is consider to low or not specific enough then molecular series based on the responding molecules can then be derived using the previously non responding molecules as indicators of crucial structural design features.

The second screening activity can indicate that an individual molecular could have a biological effect in a variety of disease conditions based on which targets of affected [8;9]. Having an indication of the clinical direction to proceed in can save significant amounts of time and effort. If the molecules do not meet stringent clinical parameters then the molecules can be moved in the first methodology strategies to improve response, for example change the pharmacokinetic profile and decrease toxicity.


    1.    Rodriguez-Devora JI, Shi ZD et al. Direct assembling methodologies for high-throughput bioscreening. Biotechnol J 2011; 6(12):1454-1465.

    2.    Liu T, Qian Z et al. High-throughput screening of one-bead-one-compound libraries: identification of cyclic peptidyl inhibitors against calcineurin/NFAT interaction. ACS Comb Sci 2011; 13(5):537-546.

    3.    Cavasotto CN, Phatak SS. Docking methods for structure-based library design. Methods Mol Biol 2011; 685:155-174.

    4.    Jennings A. Chemical informatics: using molecular shape descriptors in structure-based drug design. Methods Mol Biol 2012; 841:235-250.

    5.    Camus S, Quevedo C et al. Identification of phosphorylase kinase as a novel therapeutic target through high-throughput screening for anti-angiogenesis compounds in zebrafish. Oncogene 2011.

    6.    Hirai G. Development of novel types of biologically active compounds based on natural products and biomolecules. Yakugaku Zasshi 2012; 132(1):117-124.

    7.    Tang YT, Marshall GR. Virtual screening for lead discovery. Methods Mol Biol 2011; 716:1-22.

    8.    Joseph J, Seervi M et al. High throughput ratio imaging to profile caspase activity: potential application in multiparameter high content apoptosis analysis and drug screening. PLoS One 2011; 6(5):e20114.

    9.    Harris CJ, Hill RD et al. The design and application of target-focused compound libraries. Comb Chem High Throughput Screen 2011; 14(6):521-531.