Successful In Vitro Screening Strategies For Drug Discovery

In a previous eBook, we discussed approaches to successful hit finding. Here, we discuss some considerations in designing screening cascades to progress these hits and develop drug candidates. Whichever hit finding approach or methodology for designing and synthesizing new molecules you choose to develop your drug candidate, you will need a robust and flexible system to test your hypotheses in biological systems and ensure you remain on track. As you start to consider what an appropriate screening cascade should look like, it is important to define what key properties you are looking for in your candidate drug, as these will impact the choice of assays you may deploy in your screening cascade. For example:

• How important is selectivity for your chosen target?
• Are you targeting an orthosteric or allosteric binding site?
• Does the drug need to cross the blood-brain barrier?
• Is the target expressed in a single cell type?
• What are the potential on-target toxicity concerns?
  These aspects, and others, are worth early discussion to ensure that the right
  assays can be planned and introduced into the screening cascade at the
  appropriate time.