Reaction phenotyping processes

Reaction phenotyping is the study that measures quantitative contribution of a DME to total clearance of a given drug. The CYP reaction-phenotyping process requires the integration of data obtained from various in vitro systems... 

There exist some general considerations across in vitro reaction phenotyping studies for P450s and non-P450s that need to be anticipated in the process of defining incubation conditions. While protocol-specific guidance (Method Sheets 1 and 2) is a part of the latter sections of this... 

Development of models to assess chemical-induced allergic or autoimmune reactions is difficult in that both types of reactions are subject to complex processes, and are idiosyncratic in nature. Factors that must be considered include a large number of genetic as well as phenotypic, neuroendocrine, or environmental factors that are only in part related to the immune system. 

Protein function can be described on three levels. Phenotypic function describes the effects of a protein on the entire organism. For example, the loss of the protein may lead to slower growth of the organism, an altered development pattern, or even death. Cellular function is a description of the network of interactions engaged in by a protein at the cellular level. Interactions with other proteins in the cell can help define the lands of metabolic processes in which the protein participates. Finally, molecular function refers to the precise biochemical activity of a protein, including details such as the reactions an enzyme catalyzes or the ligands a receptor binds. 

The fundamental problem with selection for catalysis is that the product of an enzyme leaves the catalytic protein. Thus, even when genetic information of the catalyst is physically connected to the catalytic protein, the phenotype (i.e., the efficiency of the reaction) does not remain connected. In other words, in a mixture of catalysts of different efficiency, the information—which of the molecules has actually produced most of the product—becomes lost. As a consequence, product and enzyme have to remain physically connected for an efficient evolutionary process. 

Complexity and diversity are important characteristics of a library or compound collection as the eventual target of a compound in phenotypic screens can be any one of a multitude of diverse and complex proteins inside a ceU. Therefore, the overall design of the synthetic pathways in DOS should integrate both complexity and diversity. Structural complexity can, for instance, be generated in DOS through the use of tandem or domino reactions, processes involving a pair of... 

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