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SIRT2 Inhibitors as Novel Therapeutics for Myocardial Infarction and Ischemic Stroke and to Prevent Necrosis

Posted Jan 22 2013 7:00pm

Description of Invention:
Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. These investigators also found that genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha and RIP1 is a critical target of SIRT2-dependent deacetylation. Further studies also showed that the hearts of Sirt2–/– mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischemic injury. These results implicate SIRT2 as an important regulator of programmed necrosis and indicate that SIRT2 inhibitors may constitute a novel approach to protect against necrotic injuries, including ischemic stroke and myocardial infarction.

  • Novel therapeutics to protect against necrotic injuries.
  • Novel therapeutics to treat ischemic stroke and myocardial infarction.
  • Novel therapeutics to treat diseases in which necrosis is involved.

  • None of the currently available drugs address the necrotic damage caused due to ischemia and reperfusion.
  • Using a Sirt2 inhibitor could limit the damage caused by necrosis and contribute to accelerated recovery in patients suffering from these conditions.

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

Nisha Narayan (NHLBI)
Toren Finkel (NHLBI)

Patent Status:
HHS, Reference No. E-003-2013/0
US, Application No. 61/723,496 filed 07 Nov 2012

Relevant Publication:
  1. Narayan N, et al. [ PMID 23201684 ]

Collaborative Research Opportunity:
The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize retinoid-related orphan receptors (RORs) function in chronic diseases. For collaboration opportunities, please contact Ms. Peg Koelble at or 301-594-4095.

For Licensing Information Please Contact:
Suryanarayana Vepa Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-5020
Fax: 301-402-0220

Ref No: 2515

Updated: 01/2013

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