Enzyme drug discovery process

In general, the detection of adverse drug reactions early in the drug discovery process is becoming commonplace. So-called liability panels of receptors, hERG channel activity, and cytochrome enzymes are utilized to identify... 

The are several clearance and toxicological aspects that have to be considered in the drug discovery process such as metabolic stability, enzyme selectivity, CYP inhibition and type of inhibition. Among these factors, the prediction of the site of metabolism has become one of the most successful parameters for prediction. The knowledge of the site of metabolism enhances the opportunity to chemically modify the molecule to improve the metabolic stability. There are several approaches based on database mining, chemical reactivity, protein interaction or both that have been developed for the prediction of this property, with different degree of success and applicability. 

Identification of metabolic reactions at an early phase can significantly affect the drug discovery process, because bioavailability, activity, toxicity, distribution and final elimination all depend on metabolic biotransformations [1], Once obtained, this information can help researchers judge whether or not a potential candidate should be eliminated from the pipeline or modified to reduce the affinity for CYP antitarget enzymes. 

Drug-discovery process is a highly complex, multidisciplinary and time-consuming procedure, which typically starts from the identification of appropriate drug targets (biomolecules, enzymes, ion channels, receptors) to target validation, where it was established whether the target was of relevance for the disease under study. 

R. Ramanathan, D.L. McKenzie, M. Tugnait, K. Siebenaler, Application of semi-automated metabolite identification software in the drug discovery process for rapid identification of metabolites and the cytochrome P450 enzymes responsible for theirformation, J. Pharm. Biomed. Anal., 28 (2002) 945. 

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