Pharmacological space

The concept of "pharmacological space" provides a theoretical framework for navigating the apparently infinite number of choices in drug discovery. Pharmacological space attempts to chart the limits of chemical space, targets space, and disease space in order to reduce and systematize the search for new drugs in these spaces. Thus charting pharmacological space is an attempt to outline the areas where opportunities for new drugs may lie based on an extrapolation of the knowledge gained from experiments to date. This chapter outlines some of the recent theoretical arguments and empirical evidence for navigating target space and chemical space for drug discovery. Recent studies have also highlighted the relationship between high lipophilicity and the increased chance of toxicity via the increased target promiscuity of lipophilic molecules. The relationship between target class and the physicochemical properties of ligands is explored by calculating a set of physicochemical descriptors of hundreds of thousands of biologically active compounds across over a thousand proteins where the protein sequences assigned to each of the pharmacological targets were classified into gene families. The successful strategy of exploring pharmacological space in its widest sense is in contrast to drug discovery, which focuses on the narrow spectrum of a single disease or molecular target, but screens a wide sample of chemical space.