A3 Adenosine Receptor Agonists to Treat Chemotherapy-induced Peripheral Neuropathy

This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and related pharmaceutical compositions. 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
  • pain
 Oral dosing as these A3AR agonists are selective and not associated with cardiac or hemodynamic effects that may result from stimulation of A1 or A2A receptors.

Development Stage:
  • Early-stage
  • In vivo data available (animal)

Related Invention(s):


Kenneth Jacobson (NIDDK)  ➽ more inventions...

Dilip Tosh (NIDDK)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 8,916,570 issued 2014-12-23

Tosh DK, et al. PMID 22559880
Chen Z, et al. PMID 22345405

Collaboration Opportunity:

The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Marguerite J. Miller at 301-496-9003 or millermarg@niddk.nih.gov.

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

OTT Reference No: E-140-2008-1
Updated: Jun 13, 2012