Absent safe and effective therapeutics, many diseases remain untreatable or are treated with limited success. Why has the discovery and development of new drugs been so difficult? Setting aside our poor understanding of the human biological system, one significant problem with many small molecule drugs is that they lack sufficient selectivity for the intended target leading to unwanted and at times, unexpected side effects. Traditional discovery technologies rarely identify selective drug candidates because the technologies used typically focus on the catalytic or active site of the target protein – structures that are frequently conserved within a protein family or across a whole target class. Biotherapeutics begin to address this problem since they exhibit good selectivity. However, they pose a different series of challenges including complex manufacturing, poor absorption into cells, low tolerance and compliance and sometimes, adverse effects from unexpected individual immune responses.
At CompleGen, we use a simple genetic based discovery system that does not depend on a deep understanding of biologic networks. Nonetheless the system can efficiently identify target selective small molecule inhibitors that differentiate targets even within highly conserved protein families. In most cases, these small molecule compounds target non-conserved regions of the protein and inhibit allosteric regulation rather than catalytic activity, hence the exquisite specificity. Consequently, our drug candidates have all the advantages of small molecules coupled with the target selectivity of biopharmaceuticals.