Patent Number: 8,715,927

Title: Inhibition of DNA polymerases to augment chemotherapeutic and antimicrobial agents

Abstract: Disclosed herein is the identification of human DNA polymerase .kappa. (pol .kappa.) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL -inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol .kappa.. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol .kappa. sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.

Inventors: Lloyd; R. Stephen (Portland, OR), Minko; Irina G. (Portland, OR), McCullough; Amanda K. (Portland, OR)

Assignee: Oregon Health & Science University

International Classification: C12Q 1/68 (20060101); C12Q 1/48 (20060101); C12N 9/10 (20060101); C07H 21/00 (20060101); C07H 21/04 (20060101)

Expiration Date: 5/06/12018