Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology.

ABSTRACT: Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin's molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin

SUBMITTER: Hart T 

PROVIDER: S-EPMC4740793 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature