Defining a property profile is subjective and often leads to lengthy, interdisciplinary discussions about the criteria and their relevance. For example, is it worth sacrificing some potency to gain additional metabolic stability or solubility? However, a question that is rarely asked is, “What impact would that trade-off have on the final outcome?”, particularly given the underlying uncertainty.
This poster was displayed at the ISSX North American meeting in Baltimore, USA, 2009.
Success in drug discovery projects is dependent on making key decisions about the design and selection of compounds with an appropriate balance of many properties and hence a high chance of achieving the therapeutic goals. In early drug discovery, data on a large number of compounds and properties from a wide variety of sources, in silico and in vitro, must be integrated and assessed against a project’s requirements.
We have previously described an approach for scoring compounds, based on their likelihood of success against a profile defining the property requirements and their relative importance to a project’s objectives (see poster for references). Within this assessment, uncertainty in the data is explicitly considered; most sources of drug discovery data have significant statistical or experimental uncertainties and this information enables us to determine the degree of confidence with which we can distinguish between compounds.
In this poster, we will discuss how a rigorous scoring approach allows this question to be addressed directly. By assessing the sensitivity of the final compound selection to the property profile, criteria that have a significant effect on the ultimate decision can be identified. This, in turn, can focus attention on critical experiments, e.g. in vivo studies, that will help to identify the most appropriate profile to select high quality compounds with greater accuracy.
This poster is available as a PDF file.