engleski

CURRENT TRENDS IN ACTIVITY AND SELECTIVITY PROFILING OF THERAPEUTIC MOLECULES

Drug discovery is a long process starts with identification and validation of a new “druggable” target followed by testing many natural or synthetic compounds in assays relevant to the disease in question. A considerable portion of drug discovery process focuses on the target-specific assays, as well as those that assess off-target effects and cytotoxicity, which are all helpful in generating a broad profile of tested compounds reactivity. Carrying out numbers of studies prior to clinical trials such as improved toxicity testing in vitro and in vivo, establishing predictive translations models based on a thorough disease understanding and identifying biomarkers my help in the activity profiling of compounds with therapeutic potential. High affinity and selectivity are two of the most required properties of therapeutic molecules. Selectivity has been difficult to achieve, especially for targets that belong to large families of structurally and functionally related proteins. There are two ways by which selectivity can be improved during optimization: a chemical modification of the lead compound that improves the affinity towards the target to a higher extent than to off-target molecules, and a chemical modification that lowers the affinity of the lead compound towards off-target molecules. Maximal selectivity is achieved when both mechanisms can be combined synergistically. After high-throughput screening, hit compound identification, lead compound optimization, the drug discovery process ends with the launch of new active therapeutic molecules.

drug disovery; target-specific assays; phenotypic profiling; affinity; selectivity

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