Drug ligand-based

Distinguishing Molecules of Different Biol< ical Activities and Finding a New Lead Structure - An Example of Ligand-Based Drug Design... 

In this chapter, we briefly review various aspects of the chemical information systems used by the chemist for literature and patent searches the field of computer-aided drug design technologies, cheminformatics, as well as other applications. We place special emphases on the ligand-based techniques and only briefly mention the structure-based design technologies. 

Pozzan, A. Molecular descriptors and methods for ligand based virmal high throughput screening in drug discovery. Curr. Pharm. Des. 2006, 12, 2099-2110. 

All the aforementioned protein members of the cannabinoid system are large, membrane-bound proteins therefore, it is particularly difficult to obtain direct information about their tertiary structure. Thus, at the present time, structure-based drug design is not feasible. Detailed exploration of the SAR and subsequent ligand-based design are the most appropriate means for the development of molecular probes for these proteins. 

Typically, in vitro tests are cell- or tissue-based experiments. The aim is to study the biochemical functions of the target as a result of binding to potential drug ligands. Parameters such as ionic concentrations, enzyme activities, and protein expression profiles are studied. 

SAR by MS a ligand based technique for drug lead discovery against structured RNA targets. J Med Chem 2002, 45, 3816-3819. 

Recent examples of successful peptide-ligand based discoveries of drug-like peptidomimetics include the discovery of SST antagonists, or the discovery of non-peptidic antagonists of the recently deorphanized urotensin II receptor at Sanofi-Aventis. ° As illustrated in Fig. 3, Flohr etal. used 3D models of the NMR solution structure of cyclic peptide derivatives of Urotensin II as a template for virtual 3D pharmacophore searches which resulted into non-peptidic candidates for lead optimization. 

Cleves, A.E. and Jain, A.N. (2006) Robust ligand-based modeling of the biological targets of known drugs. Journal of Medicinal Chemistry, 49 (10), 2921-2938. 

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