'Picking out proteins and sending them into the vicious shredder that is the proteasome is a completely new mode of action for drugs, and there are many examples of it leading to effects that you just don't see (can't see!) with traditional small-molecule inhibitors. But as these things get further and further into development, and as more and more effort has been poured into them in both industry and academia, details inevitably emerge that make the whole picture more complicated.'

https://www.science.org/content/blog-post/unexpected-effects-protein-degradation