Of the drug discovery

Before we continue with the description of the drug discovery process, we introduce some terms commonly used in drug design and give their definitions ... 

A meaningful dialogue between chemists and pharmacologists is the single most important element of the drug discovery process. The necessary link between medicinal chemistry and pharmacology has been elucidated by Paton [2] ... 

This project was slightly unusual, in that the success and ROI criteria were investigated and developed ahead of the rest of the project. This led to a project that had clear goals and milestones in terms of usability and performance, set out ahead of any review of available solutions. In addition, the project had measurable criteria for the impact that the system was having on the efficiency of the drug discovery process. These criteria were then also used to establish go/no-go criteria for the implementation project. 

Influencing the efficacy or potency of chemicals is a strategy used by the pharmaceutical industry as part of the drug discovery process that can be incorporated into designing safer industrial chemicals. Efficacy is the maximal effect, either therapeutic or toxic, that a chemical can achieve. Potency is a measure of the amount of a substance that is needed to attain a given response level. Opioid analgesics are examples of where structural modifications have been used to establish a relationship between structure and activity. ... 

The attraction of lipophilicity in medicinal chemistry is mainly due to Corwin Hansch s work and thus it is traditionally related to pharmacodynamic processes. However, following the evolution of the drug discovery process, lipophilicity is today one of the most relevant properties also in absorption, distribuhon, metabolism, excretion and toxicity (ADMET) prediction, and thus in drug profiling (details are given in Chapter 2). 

Kniss, R., Revolution of the drug discovery process using laboratory-on-a-chip technology, Am. Lab., 30(24), 40, 1998. 

The last step of the drug discovery process involves the testing of lead compounds to address issues such as efficacy, bioavailability, and safety. Testing may include in vitro assays but ultimately would require a suitable disease model and studies in animals. Many compounds may need to be designed and synthesized to identify the one compound with all the desired properties. Such a compound can be advanced to preclinical studies and eventually to the clinic. 

Patents are of paramount importance to the pharmaceutical industry. At the discovery program level, chemotype patentability is one of the key requirements for continued work on a particular structural class. Decisions by venture capitalists to fund startup companies are based, in part, on the strength of their patent portfolios. The presence or absence of a single key patent can determine the future of even the largest pharmaceutical company. Patents thus are a critical, inseparable component of the drug discovery process. 

Partly due to the limited throughput of Caco-2 permeability measurements, the structure-activity evaluation of compounds tested in the hit-to-lead phase is done with minimal permeability information, at best. Given the importance of membrane permeability in drug absorption, early consideration of the permeability characteristics of hit compounds would enhance the drug-like quality, and ultimately the probability of success, of selected lead candidates. To incorporate permeability information into the hit-to-lead phase of the drug discovery process it is necessary that permeability measurements be made quickly and with small amounts of material. Thus, efforts have been made to automate and miniaturize the Caco-2 permeability assay. 

Rigorous evaluations of the commercial potential of new compmmds are a vital part of the drug discovery and development process. 

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