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Abstract

Grant Number: 5R43DK066880-02
Project Title: A2A Adenosine Receptor Agonist for the Treatment of IBD
PI Information:NameEmailTitle
THOMPSON, ROBERT D. rdt@adenrx.com INTERIM DIRECTOR OF CHEMISTRY

Abstract: DESCRIPTION (provided by applicant): Adenosine Therapeutics, LLC (ATL) is a biotechnology company started in Charlottesville, Virginia in 1999. ATL owns patents on the formulation and use of a family of potent and highly selective agonists of A2A adenosine receptors. One of these compounds, ATL146e, is a coronary vasodilator and has been developed (with the aid of SBIR funding) as a coronary artery imaging agent that has been licensed to Bristol Meyers Squibb exclusively for pharmacological imaging of coronary disease and is currently in phase I clinical trials. ATL146e and other agonists of A2A adenosine receptors exert powerful anti-inflammatory effects by actions on bone-marrow derived cells at doses far below those that are vasoactive. Dr. Fabio Cominelli and his colleagues in the University of Virginia (UVa) are experts in the study of inflammatory bowel diseases (IBD). They have found in rabbit models that ATL146e is profoundly protective against inflammation and injury that occurs as a result of ulcerative colitis. This is an SBIR-AT phase I proposal by ATL and UVa for the purpose of developing ATL146e and a second generation orally active compound as new therapies for the treatment of IBD. This concept will be tested in a relevant mouse model of IBD that has been well characterized by the Cominelli laboratory. The aims are: (1) to optimize drug dosing and timing; (2) determine if ATL146e can delay the onset of disease symptoms; (3) characterize a second generation orally active compound; (4) synthesize new compounds and radioactive analogs; and (5) determine the chemical properties, pharmacokinetics and biodistribution of drug candidates. There is a great need for improved therapies for IBD. Our goal is to begin clinical trials with a new drug for the treatment of IBD within two years and to develop a second generation compound within four years.

Thesaurus Terms:
drug design /synthesis /production, drug screening /evaluation, gastrointestinal disorder chemotherapy, inflammatory bowel disease, neurotransmitter agonist, nonhuman therapy evaluation, purinergic receptor
dosage, oral administration, pharmacokinetics, therapy design /development
SCID mouse, enzyme linked immunosorbent assay, flow cytometry, histology, laboratory mouse, liquid chromatography mass spectrometry, statistics /biometry, tissue /cell culture

Institution: ADENOSINE THERAPEUTICS, LLC
SUITE 201
CHARLOTTESVILLE, VA 22902
Fiscal Year: 2005
Department:
Project Start: 01-JUN-2004
Project End: 31-MAR-2008
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
IRG: ZRG1


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