Why so Few Drug Targets: A Mathematical Explanation?

Kyaw      Tun; Marta      Menghini; Lina      D'Andrea; Pawan      Dhar; Hiroshi      Tanaka; Alessandro      Giuliani

Abstract

The apparently paradoxical lack of correlation between the huge increase in the discovery of new potential drug targets made possible by the post-genomic sciences and new drugs development has stimulated many different interpretations. Here we illustrate the general principle of redundancy of biological pathways on hand of simplified mathematical approaches applied to different models of biological regulation. The simulation was based on the analysis of the ‘ degree of autonomy’ of network architectures in which the possibility for an external stimulus (e.g. a drug) impinging into a specific node to be sensed by the entire network, and eventually amplified up to a macroscopic consequence, was demonstrated to be limited to strictly linear pathways. The implications of such a result for poly-pharmacology and computational approaches to drug development are described as well.

Keywords: Systems biology, multiple targets, drug development, pharmacology, networks, linear topology, Mitogen Activated Protein Kinase (MAPK) cascade, simulation, computational approaches, Michaelis-Menten paradigm