Inverse pharmacology: Approaches and tools for introducing druggability into engineered proteins

This is a review of the field of Inverse Pharmacology, a field which my former boss at Edinburgh - Professor Jamie Davies - has been instrumental in developing.

Briefly, traditional pharmacology involves finding some 'target' in the body (a protein typically) that we want to activate/inhibit, and then searching for small molecules which can be shown to have some interaction with that target. The molecule is then developed into a drug.

In inverse pharmacology, you instead start with the small molecule that you wish to use, and then try and construct a protein which will respond to it, allowing for therapeutic proteins to be developed which can be activated by administering this small molecule. The advantage being, you can start with a small molecule that you know has no adverse medical effects, rather than having to create a new one and then exhaustively (and expensively) testing it for such effects.

The review covers the SynPharm tool that I created during my time working for Jamie, a web app which assists in identifying these drug responsive modules. This is the reason for my name being on the paper, but as I have written about this previously, I will not repeat myself here.

The review also gives details of a parallel piece of work done by my colleague Dr. Alazne Dominguez, in which the concept of Inverse Pharmacology was actually put into practice. This is a very exciting paper, detailed here, which provides important real world evidence that the concept can work in practice.