In silico pharmacology

Ekins, S., Mestres, J., Testa, B. In silico pharmacology for drug discovery methods for virtual ligand screening and profiling. Br. J. Pharmacol. 2007, 152, 9-20. 

Mestres, J., Couce-Martin, L., Gregori-Puigjane, F Cases, M. and Boyer, S. (2006) Ligand-based approach to in silico pharmacology nuclear receptor profiling. 

Vidal, D., Garcia-Serna, R., and Mestres, J. (2011) Ligand-based approaches to in silico pharmacology Methods Mol Biol (Clifton), 672, 489-502. 

Mestres J, Martin-Couce L, Gregori-Puigjane E, et al. Ligand-based approach to in silico pharmacology Nuclear receptor profiling. J Chem Inf Model 2006 46 2725-2736. 

In particular, in silico methods are expected to speed up the drug discovery process, to provide a quicker and cheaper alternative to in vitro tests, and to reduce the number of compounds with unfavorable pharmacological properties at an early stage of drug development. Bad ADMET profiles are a reason for attrition of new drug candidates during the development process [9, 10]. The major reasons for attrition of new drugs are ... 

During the early stages of drug discovery, a suitable candidate must be selected from a limited number of structurally related compounds that may have a similar pharmacological profile. At that point, information from in vitro systems would provide important and particularly useful selection criteria. However, results from in vitro models are often not yet available at the early phases of development, or they exist only for a limited number of compounds. Accordingly, there is an urgent need for in silico methods that would allow prediction of the pharmacological properties in humans from the experimental model systems. 

Terstappen, G. and Reggiani, A. 2001. In silico research in drug discovery. Trends in Pharmacological Sciences 22(1), 23-26. 

The use of animals for pharmacological and toxicological studies has yielded invaluable information for drug development. However, many drug candidates failed in Phase I and II clinical trials because the animal models were insufficient to represent human systems and functions for some drugs. Efficacy and acceptable toxicities derived from animal models were not replicated in humans (Exhibit 5.8). In recent years, the direction in development of drugs has shifted toward the use of ex vivo, in vitro assays and even in silico methods. Nevertheless, some tests must stiU be confirmed in animals. 

---