During target evaluation, researchers study disease mechanism and underlying biological pathways, which lead to the identification and characterization of drug targets. The knowledge gained from these studies allows definition and separate targeting of upstream or downstream targets. In addition, knowledge of biological pathways and their relation to each other helps researchers understand side effect profiles.
Interfering RNA or RNAi is a gene silencing phenomenon that can also assist in target evaluation. The phenomenon is triggered when double-stranded RNAs (dsRNAs) degrade homologous messenger RNA (mRNA). Specific dsRNAs are processed into small interfering RNA (siRNA) which initiates cleavage of the homologous mRNA via a RNA-induced silencing complex (RISC). Introduction of siRNA into cells leads to inhibition of the biological function encoded in the targeted mRNA. This method can be used to help evaluate the role of validated and new targets in biological pathways of disease.
Targets are also evaluated for drugability-how well a compound can access the target or by the efficacy a compound can achieve. Inhibition or modulation of selected targets can lead to the same lead compound with fewer side effects or better drugability. A long list of parameters influences drugability, including cellular location, development of resistance, transport mechanisms, side effects, and safety concerns.
A number of Molecular Devices Systems can help researchers with target evaluation studies.
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