Compositions and methods of use of A2 adenosine receptor (AR) agonists for treating conditions modulated by A2A and A2B ARs including myocardial ischemia, reperfusion injury, cystic fibrosis, erectile dysfunction, inflammation, restenosis and septic shock

Four adenosine receptor subtypes exist, namely A1, A2A, A2B and A3, each with different functions, tissue distributions and ligand coupling abilities.  While activation of A2B AR can induce angiogenesis, reduce vascular permeabilization, increase production of the anti-inflammatory cytokine IL-10, increase chloride secretion in epithelial cells or increase release of inflammatory mediators from human and canine mast cells, there still remains a need for A2B receptor agonists for clinical use.

 

Recognizing that an unmet medical need exists, the inventors synthesized an assortment of adenosine derivatives with the goal of preparing highly potent and selective A2B receptor agonists.  They identified a compound as a full agonist at the A2A and A2B adenosine receptors, capable of reducing infarct size in rabbit hearts induced by 30 minutes of ischemia.  As activation of A2A and A2B receptors induces a cardioprotective effect and this compound activates both A2A and A2B receptors, this compound may be beneficial for protecting against myocardial ischemia/reperfusion injury.

 

Available for licensing and commercial development are compositions and methods of use of A2 adenosine receptor (AR) agonists for treating conditions modulated by A2A and A2B ARs including myocardial ischemia, reperfusion injury, cystic fibrosis, erectile dysfunction, inflammation, restenosis and septic shock.

 

Applications:

• Potential treatment for heart attacks
• Potential treatment of septic shock, cystic fibrosis and erectile dysfunction
• Potential treatment for medical conditions that would benefit from changes in vascular tone

Early Stage

• U.S. Provisional Application No. 60/947,066 filed 29 Jun 2007 (HHS Reference No. E-218-2007/0-US-01)
• U.S. Provisional Application No. 60/950,250 filed 17 Jul 2007 (HHS Reference No. E-218-2007/1-US-01)

 

Inventors:

Kenneth A. Jacobson et al. (NIDDK)

 

 

Licensees Sought:

Available for licensing.

 

Collaborative Research Opportunity:

The NIDDK Laboratory of Bioorganic Chemistry is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize A2A and A2B adenosine receptor agonists.  Please contact Rochelle S. Blaustein at (301) 451-3636 or Rochelle.Blaustein@nih.gov for more information.