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


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.

Potential Commercial Applications: Competitive Advantages:
  • 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 Stage:
  • Early-stage
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:

Nisha Narayan (NHLBI)  ➽ more inventions...

Toren Finkel (NHLBI)  ➽ more inventions...


Intellectual Property:
US Application No. 61/723,496

Publications:
Narayan N, et al. PMID 23201684

Collaboration 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 koelblep@mail.nih.gov or 301-594-4095.


Licensing Contact:
Admin. Licensing Specialist (ALS),
Email:
Phone:

OTT Reference No: E-003-2013-0
Updated: May 9, 2018