Why hasn't Struture-based drug design produced any blockbuster molecules yet?
For my Pharmacology class I am required to write a review paper this semester and I had decided to cover the use of x-ray structure of beta 2-adrenergic receptor to screen and design ligands. Obviously, I would be basing most of the paper on the work that has been done in Dr. Kobilka's lab at Stanford University. Their recent paper - "Structure-based discovery of Beta 2-adrenergic receptor ligands" in PNAS is what got me interested into this relatively new field of virtual screening. This paper deals with the use of virtual screening techniques to determine a list of probable targets using standard docking software programs.
My Prof. wants me to cover the clinical implications of these compounds obtained through virtual screening, and rightly so, considering my course is quite clinical-based. But unfortunately, I haven't found a single compound which has been obtained from these screens that has reached the market or even the clinical trials stage. Which makes me wonder as what might be stopping the Big Pharma from turning these into pharmaceuticals? Is it because that they comprise of no new therapeutic advantages (certainly may have some advantage) over the ligands previously obtained from traditional chemical synthesis and HTS? But I wouldn't think so considering the fact that this has never stopped them from developing such vast heaps of me-too drugs over the past 50 years. I guess they are still trying to get a feel of these compounds and its just too early for such questions.