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Method of Treating Hepatitis C Virus Infection With a Small Molecule CHK2 Inhibitor

Posted Mar 22 2012 8:00pm

Description of Invention:
DNA damage sensors such as Checkpoint Kinase 2 (Chk2) are key regulators of the cellular DNA damage response that limits cell-cycle progression in response to DNA damage. It has been reported that these DNA damage sensors also play a key role in Hepatitis C virus (HCV) replication. The subject technology are small molecule CHK2 kinase inhibitors that have been shown to have promising activity against HCV replication. The compounds were discovered by high throughput screening of chemical libraries with more than 150,000 compounds. These novel compounds can potentially be used in combination with other anti-HCV drugs or interferon and represent a novel target for treating HCV. In vitro antiviral assay data, as well as preliminary in vitro and in vivo pharmokinetic data are available upon request.

Applications:
The subject technology can potentially be developed into anti-HCV therapeutics, particularly in combination with other anti-HCV therapeutics.

Advantages:
The subject technology represents a novel and promising target for treating HCV infection and thus, has the potential to increase the efficacy of other HCV antivirals that directly target HCV in a multi-drug formulation. Furthermore, since the subject technology targets a cellular protein necessary for HCV replication and not the virus itself, the emergence of viral resistance against the subject technology could be low or more delayed.

Development Status:
  • Early-stage
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Yves G Pommier (NCI)
Robert H Shoemaker (NCI)
Dominic A Scudiero (NCI)
Andrew G Jobson (NCI)
David S Waugh (NCI)
George T Lountos (NCI)


Patent Status:
HHS, Reference No. E-224-2011/0
US, Application No. 61/551,742 filed 26 Oct 2011


Related Technologies:
US, Application No. 11/989,737 filed 29 Jan 2008, Reference No. E-211-2005/0 , with corresponding applications in Europe, Canada, and Australia
US, Application No. 60/703,556 filed 29 Jul 2005, Reference No. E-211-2005/0


Relevant Publication:
  1. Jobson AG, et al. [ PMID 17616632 ]
  2. Jobson AG, et al. [ PMID 19741151 ]
  3. Lountos GT, et al. [ PMID 19177354 ]
  4. Lountos GT, et al. [ PMID 21907711 ]
  5. Lountos GT, et al. [ PMID 21963792 ]



For Licensing Information Please Contact:
Kevin Chang Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: changke@mail.nih.gov
Phone: 301-435-5018
Fax: 301-402-0220


Ref No: 2388

Updated: 03/2012

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