Processes of Drug Discovery

PROCESSES OF DRUG DISCOVERY

Discovery

The initial step of drug discovery involves the identification of new active compounds, often called ‘hits or leads’, which are found by screening many compounds of synthetic or natural sources, such as plants, animals, or microorganisms for their targeted biological properties. More often, the hits use to come from synthetic sources, such as historical compound collections and combinatorial chemistry.

Optimization

The second step in drug discovery involves further chemical alterations on structure activity relationship (SAR) basis to enhance the biological and physicochemical properties of a given candidate compound library. The chemical modifications can improve the binding property and interaction (pharmacophores) of the drug candidate compounds, their affinities, and pharmacokinetics, or indeed, their reactivity and stability during their metabolic degradation. Among the methods that have contributed to the quantitative metabolic prediction, a recent example is substrate product occurrence ratio calculator (SPORCalc).

The identified pharmacophores play an important role in finding the lead compounds, which exhibit the most potency, the best pharmacokinetics, and the least toxicity. The QSAR molecular modelling tools, such as comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), which leads to tabulated data and firstand second-order equations. Among the theories related to these, the most relevant being Hansch’s analysis that involves Hammett electronic parameters, steric parameters, and LogP (lipophilicity) parameters.

Development

The final step involves rendering the lead compounds that are suitable for use in the clinical trials after their successful pharmacodynamic optimization in clinical trials, the optimization of the synthetic route for bulk production, and the preparation of a suitable drug formulation.