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ANTAGONISTS OF A2B RECEPTORS IMPROVE INSULIN SENSITIVITY

Award Number: R44DK059677
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2004
PERIOD OF PERFORMANCE END DATE: 03/31/2006

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ANTAGONISTS OF A2B RECEPTORS IMPROVE INSULIN SENSITIVITY - DESCRIPTION (provided by applicant): This is a phase II SBIR grant to develop a new therapy for the treatment of type II diabetes. Adenosine Therapeutics, LLC (ATL) is a biotechnology company started in Charlottesville, Virginia in 1999. ATL owns patents on the formulation of selective antagonists of A2B adenosine receptors (A2BAR). Dr. Kathryn LaNoue of Penn State University discovered that A2BAR blockers lower blood glucose in insulin resistant animals. A use patent to this discovery has been licensed to ATL. In the phase I portion of this grant we found that novel highly selective A2BAR blockers lower blood glucose in mice or rats, but the efficacy of the early compounds was limited, probably due to very low aqueous solubility and low bio availability. A new family of antagonist that has much higher solubility has recently been formulated at ATL and found to be very effective in lowering blood glucose. In a continuing collaboration between ATL and the LaNoue laboratory, we now propose to identify a therapeutic candidate for the treatment of diabetes. More compounds will be screened for potency and selectivity in radio ligand binding assays. Promising compounds will be screened to determine their potency and efficacy in bioassays to lower blood glucose in insulin resistant animals. The most active compounds will be evaluated for oral activity and for pharmacokinetic and pharmacodynamic properties. A few compounds will be evaluated in euglycemic clamp studies with Zucker rats. Our goal is to identify a lead compound that has good characteristics as a potential new drug. If we identify such a compound our plan is to partner with a large pharmaceutical company for clinical trials.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2005 ( Subtotal = $697,156 )
2005	2005	ADENOSINE THERAPEUTICS, LLC	PO BOX 4632	CHARLOTTESVILLE	VA	22905	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/25/2005	NON-COMPETING CONTINUATION	$697,156
														Subtotal = $697,156

Issue Date FY: 2004 ( Subtotal = $727,289 )
2004	2004	ADENOSINE THERAPEUTICS, LLC	PO BOX 4632	CHARLOTTESVILLE	VA	22905	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/9/2004	COMPETING CONTINUATION	$727,289
														Subtotal = $727,289

Grand Total All Awards = $1,424,445

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ANTAGONISTS OF A2B RECEPTORS IMPROVE INSULIN SENSITIVITY

Award Number: R44DK059677

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2004

PERIOD OF PERFORMANCE END DATE: 03/31/2006

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