Mechanism and structure-based drug designs
You can start from nothing, and still be successful!
A wonderful and demonstrably successful way to develop new drugs or new tool compounds can be based purely from biochemical mechanism.
For example, you may have identified a protease that acts to exacerbate a disease state. You want to find the protease inhibitor for it?
We can simply take Nature’s own substrates and engineer non-scissile mimetics. A whole field of clinically approved HIV treatments was spawned from this approach.