Project Considerations

Rydzewski, Robert M.

This chapter presents a brief overview of how new drug discovery projects begin, some of the science and business decisions that go into them, what types of projects researchers can expect to see, and how targets are identified and validated. Projects tend to have some commonalities that allow most of them to be divided up into several bins, if the bins are made large enough.. The term target validation can mean different things to different people. To a chemist proposing a new project it might refer to affirmative evidence from a mouse knockout or even just an RNA interference experiment in cells. To a clinician it probably means no less than proven statistically significant efficacy by a drug in large-scale, controlled human trials. Target validation, that is, systematically building up evidence that the interaction of a proposed target with an agent like a small molecule or a monoclonal antibody (mAB) can have a therapeutic effect in a human disease state, is often far from trivial. It represents an ongoing, labor-intensive process that can be rate-limiting, but is necessary to avoid disastrous losses in time, money, and manpower that occur when a clinical drug fails to work because its target is not at all crucial to disease progression or symptoms. Target identification, in this case the process whereby a new target is first proposed based on some minimal evidence, is less cumbersome but still requires devoted resources. The beauty of working on a project based upon an already established target is that both of these steps can be skipped.