There was recent article in Nature Reviews Drug Discovery entitled “Small molecules against RNA targets attract big backers.” The article described several molecules that came out phenotypic screeening programs at Novartis, Merck, and Pfizer. These molecules target RNA instead of protein. “This was a huge surprise to us,” says RAjeev Sivasankaranm head of neurosciences group at Novartis. The group had been trying for years to figure out how a small molecule LMI070 works.
It should have been no surprise. RNA is turning out to be far more important than protein in cellular biology. I suspect that many of the molecules we currently think work through proteins will turn out to actually work through RNA. And many of the molecules where we have been unable to explain the mechanism of action (and there are many, including gold), will turn out to work via RNA.
Since we used to think protein was the most important class of target for drugs, we forced most of the molecules into that paradigm. Now that it’s becoming clear that this is not the case, our understanding of the drugs’ mechanism of action are being transformed.