Drug repurposing viewed through an information theory and traditional thermodynamics lens

Drug repurposing is a potentially cheap, rapid and authentic aspect of drug development at a time when the need for new therapeutic solutions is high. Issues such as scale, diversity, and complexity associated with drug repurposing are areas well covered elsewhere. The interwoven issues of drug pleiotropy, including the serendipitous discovery of drug pleiotropy are less well described and we believe it is fundamental to our understanding of drug repurposing.

Pleiotropy has been a cornerstone in genetics research for decades and has described the importance of the phenomena of single loci affecting multiple traits. It is apparent that pleiotropy, as a phenomenon representing the existence of forms of connectivity involving one entity to several or many entities, is widespread. In mammalian physiology and cell biology, examples of pleiotropy are abundant and often characterised by the exploitation of the extension and reach from a single gene-based entity to embrace multiple functions, without compromising specificity. Pleiotropy is thus seen as an efficient way of propagating information and maintaining the specificity and unambiguous nature of the instructional message, and serendipity contributes significantly to understanding pleiotropy and therefore drug repurposing.

In this presentation, we discuss in thermodynamic terms, serendipity as a representation of more information than was thought available with the rational design of the drug (Shannon entropy). Repurposing drugs facilitates information and instructional transfer in accordance with information theory and the requirements of Gibbs free energy of binding. Therefore, therapeutics are fundamental facilitators of information and instructional transfer and further pleiotropic information transfer could underpin drug repurposing. Thus, the distinguishing features of pharmacology and information theory may be intimately linked. With advances in machine learning with its strong links to information theory it may be an appropriate time to employ these approaches in drug repurposing.