Lead optimization in the nondrug-like space

Drug-like space might be more densely populated with orally available compounds than the remaining chemical space, but lead optimization can still occur outside this space. Oral drug space is more dynamic than the relatively static drug-like space. As new targets emerge and optimization tools advance the oral drug space might expand. Lead optimization protocols are becoming more complex with greater optimization needs to be satisfied, which consequently could change the role of drug-likeness in the process. Whereas drug-like space should usually be explored preferentially, it can be easier to find oral drugs for certain targets in the nondrug-like space.