Designing a safe and effective drug is an extremely difficult process because researchers are essentially trying to find one molecule that satisfies a large number of requirements or properties. For example, does it bind to the target of interest? Does it bind to other targets and create side effects? Is it effective? Will it be toxic? How is it metabolized? Does it interact with other drugs? Is it easy to take? How quickly will it be cleared from the body?
To make it even more challenging, when a chemist modifies one part of a molecule to satisfy a particular requirement (eg, selective binding), another property could be altered as well, including undesirable properties such as increased toxicity. Sometimes it is well understood how a specific modification will impact the properties of the drug candidate, other times it is unanticipated. Imagine being faced with a large panel of dials, such as a cockpit panel, where each dial needs to have its value within a unique range in order to land a plane safely. But when you turn a certain dial to be in its required range, other dials are inadvertently turned as well and are no longer in their optimal range. When designing a drug, the hidden connections between properties, of how these “dials” are interrelated, can greatly complicate the process of trying to get all the “dials” to be in their optimal range. Often, researchers will need to iterate through tens of thousands of molecules to find one with all its “dials” in the right spot. The end result of this process is to have a potent and safe drug candidate that can be brought into preclinical development.