Technology ID
TAB-3846

Selective A3 Adenosine Receptor Agonists for the Treatment of Chronic Neuropathic Pain and Other Conditions

E-Numbers
E-140-2008-0
Lead Inventor
Salvemini, Daniela (Saint Louis University School of Medicine)
Co-Inventors
Tosh, Dilip (NIDDK)
Jacobson, Kenneth (National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK))
Applications
Therapeutics
Therapeutic Areas
Oncology
Immunology
Dermatology
Cardiology
Development Stages
Pre-clinical (in vivo)
Lead IC
NIDDK
ICs
NIDDK

This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. A3AR agonists have been a promising strategy for the treatment of various diseases. A3AR agonists can reverse neuropathic pain by modulating the production of anti-inflammatory cytokines such as IL-10. A3AR agonists can also induce apoptosis of cancer and inflammatory cells by disrupting the Wnt and NF-KB signaling pathways. The current invention includes A3AR-selective agonists that are methanocarba derivatives. This class of compounds has been shown to be highly selective for A3AR (>3000-fold affinity versus A1AR and A2AAR). This selectively is retained in mice (400-fold affinity versus A1AR), facilitating preclinical development.

Commercial Applications
A3AR-selective agonists are currently in advanced clinical trials for the treatment of hepatocellular carcinoma, autoimmune inflammatory diseases (such as rheumatoid arthritis), psoriasis, dry eye disease, and other conditions. Other potential applications of such agonists could be osteoarthritis, Crohn's disease, ischemia, and other inflammatory disorders.

Competitive Advantages
This class of compounds produced full agonists of the human A3AR of nanomolar affinity that were consistently highly selective (>3000-fold vs. A1AR and A2AAR). The selectivity at mouse A3 receptors is retained but lower. The compounds are still effective in vivo in reducing or preventing the development of neuropathic pain. Phenotypic screening has identified in vivo activity of specific C2 substituents in a chronic neuropathic pain model. Opioid analgesics in combination with A3 agonists have reduced side effects.

Request More Info

Licensing Contact:
Tong, Betty
tongb@niddk.nih.gov

Related Inventions

  • E-140-2008-0
    E-140-2008-1
    E-742-2013-0

Publications

Collaborations

  • Licensing
  • Collaboration

Collaboration Description

  • We are seeking statements of capability or interest from parties interested in collaborative research to further developer, evaluate, or commercialize this technology.
Date Published