Species-Independent A3 Adenosine Receptor Agonists Which May Be Useful for Treating Ischemia, Controlling Inflammation, and Regulating Cell Proliferation

This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and pharmaceutical compositions comprising such nucleosides. The A3 adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A3 versus A1 in humans while retaining at least 400x selectivity for A3 versus A1 in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3 agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.

Potential Commercial Applications: Competitive Advantages:
  • cardiac arrhythmias or ischemia
  • inflammation
  • stroke
  • diabetes
  • asthma
  • cancer

Development Stage:
Research quantities of compounds have been synthesized and tested for receptor selectivity.

Related Invention(s):


Kenneth Jacobson (NIDDK)  ➽ more inventions...

Artem Melman (NIDDK)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 8,735,407 issued 2014-05-27
US Application No. 61/040,985
US Application No. 12/935,461

Melman A, et al. PMID 18424135

Collaboration 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 A3 Adenosine Receptor Agonists. Please contact Marguerite J. Miller at 301-496-9003 or millermarg@niddk.nih.gov for more information.

Licensing Contact:
Betty Tong, Ph.D.
Email: tongb@niddk.nih.gov
Phone: 301-451-7836

OTT Reference No: E-140-2008-0
Updated: Sep 24, 2013