Drug Discovery and Development

Abstract

This chapter describes how medicines have been discovered in the past and comprehensively reviews how drug discovery and development are being conducted nowadays. Today, a detailed molecular understanding of the disease is of paramount importance for the successful development of new medicines. The discovery and development process can be divided into several main steps, namely target identification and validation, lead identification and optimization, pre-clinical and clinical development. The validated therapeutic target takes centre stage in this process, as it determines the mode of action of a therapy. The chapter further discusses experimental approaches to target validation and important concept related to therapeutic targets such as oncogene addiction and synthetic lethality. Once a validated therapeutic target is available the actual drug discovery process that might include serendipity, chemical modification of bioactive molecules, rational drug discovery or random screening can begin. Further development of the identified drug candidates involves the optimization of its physical and chemical properties including its absorption, distribution, metabolism and excretion (ADME) and toxicity. During preclinical development scientists evaluate if the drug candidate is safe and works, can be delivered and manufactured, and therefore can be further tested in humans. The clinical evaluation in patients is divided into three different phases with different objectives and participants. The chapter describes the design of clinical trials and the approval process for a new drug.