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THE PHARMA REVIEW (APRIL - MAY, 2008)

Drug Discovery Research in India: Opportunities and Challenges

P. Reddanna

Abstract: Coordinated regulation of metabolic processes in response to relevant internal and external factors is essential for maintenance of homeostasis. At molecular level, enzyme regulation and signal transduction pathways play crucial role in homeostasis. Any disturbance in this normal physiological process leads to the diseased state. We can say that in disease something has got out of balance and the aim of drug therapy is to restore that balance.

Drug Discovery

The approach to drug discovery requires several essential ingredients for success: (i) understanding the physiological basis of the disease, so that the target of a drug with a particular action could be projected for a therapeutically beneficial action, (ii) an explicit chemical lead, (iii) bioassay systems, which measure the desired drug activity in the laboratory, and (iv) a test system, which projects the activity of the drug in humans that can be related to a potent therapeutic treatment. With the greater understanding on physiological mechanisms of disease processes, it has become possible to take a more target based approach to drug discovery. Most of the drugs (~ 85%) in the market are targeted to proteins, which are either receptors, or enzymes or hormones in nature. As a result understanding the structure and function of proteins has become a critical component of drug discovery process. Around 45 % of the drugs in the market are targeted to receptor proteins, either agonists or antagonists. This is closely followed by enzyme proteins (28%) and hormones (11%).

The enzymes and receptors have highly specialized sites involved in molecular recognition, whereby only the appropriate molecule alone interacts with them. This leads to a very high degree of selectivity of action and hence they provide very good chemical starting points for drug discovery. Once we understand these molecular recognition mechanisms, then we can design an antagonist to block the recognition using the chemistry of the natural messenger as a lead. Thus enzymes, receptors and protein hormones are highly specialized sites involved in molecular recognition and they provide very good starting points for molecular modeling and drug design.

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