Well, I think it's true that traditionally folks trying to do rational drug discovery are better at targeting certain proteins (cell surface receptors; some enz

Well, I think it's true that traditionally folks trying to do rational drug discovery are better at targeting certain proteins (cell surface receptors; some enzymes) with small molecules than others. Also true that first generation of most drugs were discovered serendipitously and only later was mechanism understood. BUT - notion that we're at the sharp downward slope would be a surprise to most pharmas and biotechs. While there's more of an emphasis on understanding entire pathways rather than single proteins, it's still generally the goal to find a single place in the pathway where a small molecule (or antibody, or whatever) will act. It's also /really/ hard to disrupt protein-protein interactions, though it's possible.