Predicting enzyme targets for cancer drugs by profiling human Metabolic reactions in NCI-60 cell lines

Background: Drugs can influence the whole metabolic system by targeting enzymes which catalyze metabolic reactions. The existence of interactions between drugs and metabolic reactions suggests a potential way to discover drug targets. Results: In this paper, we present a computational method to predict new targets for approved anti-cancer drugs by exploring drug-reaction interactions. We construct a Drug-Reaction Network to provide a global view of drugreaction interactions and drug-pathway interactions. The recent reconstruction of the human metabolic network and development of flux analysis approaches make it possible to predict each metabolic reaction's cell line-specific flux state based on the cell line-specific gene expressions. We first profile each reaction by its flux states in NCI-60 cancer cell lines, and then propose a kernel k-nearest neighbor model to predict related metabolic reactions and enzyme targets for approved cancer drugs. We also integrate the target struc...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Limin Li, Xiaobo Zhou, Wai-Ki Ching, Ping Wang
• Keywords: BMCBI 2010, Drugs, Metabolic, Metabolic Reactions