The process of drug discovery and the Yin/Yang of small-molecule/biotech option

摘要

AbstractUntil the mid 90ties of last century, talking about drug discovery and development was essentially referred to the process of discovery and development of small-molecule chemical entities. All the language, common procedures and technicalities were inherent to this setting; concepts such as drug design, hit and lead compounds, high-throughput screening were referring to the typical mode of investigating and selecting small-molecule candidates through pre-clinical development. At that time, the arrival of the first biotech drugs has markedly changed the landscape, requiring a completely new approach to pre-clinical development. Issues related to drug-receptor interaction or to the selection from a huge number of candidates were obviously simplified to a minimum compared to the small-molecule setting. Conversely, the pharmaceutical development of biotech drugs showed far higher complexity, and the overall high complexity of industrial production initially represented a major issue to justify the high costs of biotech drugs.Besides, the technical impossibility to make ‘generics’ of biotech drugs was another strong reason driving Pharma companies toward the development of biotech drugs. Thus, in the beginning the early development phases of small-molecules or biotech drugs really stood as two distant planets. However, by the time such initial distances have been progressively reduced. From the biotech site, the technique of phage-display library scanning and similar approaches made the selection of biotech lead compounds resembling more closely what happens with small molecules; also the complexities and high costs