Investigating The Structure And Organization Of A Drug Target Network

Investigating the Structure and Organization of a Drug-target Network

Nowadays, drug discovery frequently relies on computer modeling techniques. Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. Due to the exponential growth of molecular data and fast advancement in technologies, the efforts of drug discovery have been tremendously amplified. The mode of action of a drug on its targets can often be classified as being positive (activator, potentiator, agonist, etc.) or negative (inhibitor, blocker, antagonist, etc.). The aim of this thesis is to contribute to the field of "network pharmacology" by introducing the idea of signed drug-target network and investigating its properties. The signed edges of a drug-target network can be used to explore in a systematic way the combined mechanisms of action of multiple drugs on the ensemble of common targets. In this thesis it is shown that for the signed human drugtarget network the majority of drug pairs tend to have synergistic effects on the common targets, i.e., drug pairs tend to have modes of action with the same sign on most of the shared targets, especially for the principal pharmacological targets of a drug. Methods are proposed to compute this synergism, as well as to estimate the influence of the drugs on the side effect of another drug.

ONDCP Reauthorization

Annual Report of the Organized Crime Drug Enforcement Task Force Program