Small Molecule MRS5474 with Anticonvulsant Activity for Treatment of Epilepsy

Adenosine modulates many physiological processes by activating specific adenosine receptors. These adenosine receptors play a critical role in the regulation of cellular signaling and are broadly distributed throughout the body. Thus, the ability to modulate adenosine receptor-mediated signaling is an attractive therapeutic strategy for a broad range of diseases. This technology relates to a group of compounds that display high affinity and specificity for the A1 adenosine receptor subtype.

One of the compounds, MRS5474, displays anticonvulsant activity in the 6 Hz animal model of clonic seizures. In the minimal behavioral toxicity test using the rotarod, no toxicity (zero out of eight mice) was observed at all doses tested up to 30 mg/kg, the highest dose tested, which was nearly completely protective (seven out of eight animals) in the 6 Hz model. MRS 5474 also tested well in the corneal kindled mouse model to examine its effect on focal seizures.

Potential Commercial Applications:		Competitive Advantages:
Oral anticonvulsant drug. Provides a means to mimic A1AR mediated signaling in vitro and in vivo.		These small molecules display increased specificity for the A1 type of adenosine receptors, which may reduce unwanted side effects previously seen in A1AR agonist therapies. The physical properties of these molecules are drug-like, which makes them attractive for pre-clinical development.

Development Stage:

• Early-stage
• In vitro data available
• In vivo data available (animal)

Related Invention(s):
E-285-2008-0


Inventors:

Kenneth Jacobson (NIDDK)  ➽ more inventions...

Dilip Tosh (NIDDK)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 9,181,253 issued 2015-11-10

Publications:
Tosh DK, et al. PMID 22921089

Collaboration Opportunity:
The NIDDK is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MRS5474, A1 adenosine receptor agonist for treatment of seizures. For collaboration opportunities, please contact Marguerite Miller at Marguerite.Miller@nih.gov.


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

OTT Reference No: E-285-2008-1
Updated: Aug 31, 2016