Modern Drug Discovery

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Chapter: Medicinal Chemistry : Introduction to Medicinal Chemistry

A new approach to drug discovery is to understand how the diseases and infections are controlled at the molecular and physiological level and to target specific entities based on this knowledge.


MODERN DRUG DISCOVERY

A new approach to drug discovery is to understand how the diseases and infections are controlled at the molecular and physiological level and to target specific entities based on this knowledge. This process of drug discovery involves the identification of the candidates, synthesis, characterization, screening, and assays for its therapeutic efficacy. Once a compound has proved its value in these tests, the process of drug development starts prior to the clinical trials.

Despite the advances in technology and understanding of the biological systems, drug discovery is still a long process with a low rate of new therapeutic discoveries. Information on the human genome, its sequence, and what it encodes has been hailed as a potential windfall for drug discovery, promising to virtually eliminate the bottlenecks in therapeutic targets that have been one of the limiting factors on the rate of therapeutic discovery.

Targets New and Established

Those targets for which there is good scientific understanding, supported by lengthy publication history of both as to how the target functions in normal physiology and how it is involved in human pathology are called as ‘established targets’. It is directed to the extent of background information available on a target, in particular, functional information and does not imply that the mechanism of the action of drugs that are thought to act through particular established targets is fully understood. Less investment is, generally, required to develop a therapeutic directed against the target for which more such information is available, The process of gathering such functional information is called ‘target validation’ in pharmaceutical industry parlance. Established targets provide information on the chemical feasibility of developing a small molecular therapeutic against the target, and can provide licensing opportunities and freedom to operate indicators with respect to small molecule therapeutic candidates.

In general, ‘new targets’ are those targets that are not ‘established targets’, but which have been or are the subject of drug discovery campaigns. These typically include newly discovered proteins or proteins whose functions have now become clear as a result of basic scientific research. The majority of the targets currently selected for drug discovery efforts are proteins. Two classes of proteins predominate: G-proteincoupled receptors (GPCRs) and protein kinases.

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