I hope that in decades to come that our current drugs look as crude as I think they will. For all of our knowledge and all our equipment, we still don't have much of an idea of what we're doing around this industry, not compared to the sum of what there is to know.
Most of our drugs (by "most", I mean way over 95%) bind to proteins. And that's fine, as far as it goes, because proteins sure are important things. We love them because many of them have pockets and cavities that fit small molecules, of course, giving us a tremendous leg up. But it's not that we've figured out how to attack them reliably, though, when you consider that there are many entire classes that have never been successfully targeted (phosphatases, to pick an outstanding example).
Once you get out of the small-molecule-binding zone, you're out in the wild, wide open prairie of protein-protein interactions. So far, we can't really affect those with small molecules, not worth squat. It's a shame, because the number of potential targets goes up by orders of magnitude when you take these interactions into account - well, assuming that we figure out what these zillions of interactions are actually doing, which is quite another problem in itself. But they're doing something, that's for sure, and we'd love to be able to step in for our own purposes.
But protein-protein interactions are only the beginning. If you want to go upstream and alter protein production at the source, then you're going to be targeting protein-DNA and protein-RNA) interactions. The list of known drug-like molecules which can do that is pretty short, and the success rate has been pretty small (more on the reasons for that in another post). And this is another area where only small regions of interaction space have been mapped out and understood, so there's room to work in - if you can find a way to make things work.
Don't stop there, though. We really don't pay enough attention to carbohydrates in all their forms, but they've got some crucial roles, too. Contacts involving complex polysaccharides are key to immune function, and small molecules that can affect them are rare indeed. A whole landscape of inflammation targets is waiting for someone who can get a handle on this stuff. And I haven't even talked about lipids, because frankly, we don't understand a lot of what they're doing. Protein-lipid interactions have been targeted, but can be a hard row to hoe, since the small molecules that work tend to look awfully greasy themselves. But there may also be lipid-lipid interactions that no one has ever noticed, and how you'd target those therapeutically is a real stumper.
There are even more exotic combinations, but you get the idea. When you look at the whole medicinally active universe, it's clear that we've only done successful work in a few small parts of it. An interesting and rewarding time awaits those who can extend those holdings. . .