Drug Design and Development

Modern drug design and development consists of several phases. Initially, a number of potential targets are identified using  molecular biology/  proteomics/genomics. Subsequently, the functional relationship between the disease and the target is investigated  ( target validation) using cultured human cell lines and animal models. A molecular target may be regarded as validated if it can be demonstrated that there is a critical relationship between the target and the disease and if modulation of the target activity has a substantial effect on the outcome of the disease. Modulators of the validated targets may be found by screening a combinatorial library or by computational studies. Candidate molecules identfied in the initial screen may be optimized for optimal pharmacodynamic response and also to improve their ADMET properties (Absorption, Distribution, Metabolism, Elimination and Toxicity). Finally, clinical trials are carried out to determine the safety and efficacy in humans.

Reading list for Drug design and development

Combinatorial chemistry

Silverman: Organic chemistry of drug design and drug action

R.S.Wilson and A.Czarnik


Measures of diversity

A. Leach. Molecular Modeling.


High throughput screening

DA Pereira and JAWilliams, British Journal of Pharmacology (2007) 152, 53–61

Use of comparative genomics 

R.C.Hardisonhttp://biology.plosjournals.org, Volume 1 | Issue 2 | Page 156

S.T.Cole. Eur Respir J 2002; 20: Suppl. 36, 78s–86s

Gene expression profiling for Target Validation.


A.Wise, K.Gearing and S.Rees, DDT Vol. 7, No. 4 February 2002

RNA interference and Gene knockdown in mice for target validation.

S.D. Buckingham, B.Esmaeili, M.Wood and D.B.Sattelle, Human Molecular Genetics, 2004, Vol. 13, ReviewIssue 2

Gene knockouts in mice for target validation.

Primrose and Twyman. Principles of gene manipulation and genomics.

Metcalf and Dillon. Target validation in drug discovery.

Transgenic animal models for target validation

M.Singh and L.Johnson, Clin Cancer Res 2006;12(18) September 15, 2006

Animal models for important therapeutic areas. (Other than mice).

Trans NIH zebrafish initiative

Metabonomics metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification.

Metabolomics metabolomics is the measurement of metabolite concentrations and fluxes and secretions in cells and tissues in which there is a direct connection between the genetic activity (gene expression), protein activity (proteome) and the metabolic activity itself.   The term metabolomics is preferred when the goal of the study is to characterize the entire set of metabolites.