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Abstract

Abstract: DESCRIPTION (provided by applicant): This project develops A2A adenosine receptor (A2AAR) agonists as adjuncts to antibiotics for the treatment of anthrax septicemia. It responds to the urgent need for better treatment of highly lethal infections by this bioterrorism/biowarfare agent. Phase I has two aims, pharmaceutical development and documentation of efficacy in clinically relevant settings. The goal of Aim I is to identify one lead and two to three backup compounds for development. It applies USP criteria to the screening of the company library of 50 proprietary A2AAR agonists for pharmaceutically relevant factors such as in vitro efficacy, solubility, stability to heat, light and pH, followed by secondary screens to document physical characteristics such as pKa, hydrophobicity and affinity for plasma proteins. The goal of Aim 2 is to demonstrate preliminary efficacy. It develops a mouse model of anthrax toxin sepsis by: (1) dose-ranging studies on anthrax lethal toxin (LT); (2) dose-ranging studies of A2AAR agonist protection against LT sepsis; (3) studies of the effect of delay in administration of A2AAR agonist on protection against LT sepsis, and (4) documentation that the A2AAR specifically mediates the protective effect of these agonists. Attaining both aims will argue for continuing on to Phase II for additional assessments of efficacy as well as of pharmacokinetics and metabolism.

Thesaurus Terms:
anthrax, antibacterial agent, blood toxicology, drug design /synthesis /production, drug screening /evaluation, purinergic receptor
bacterial toxin, dosage, pharmacokinetics
laboratory mouse

Institution:	ADENOSINE THERAPEUTICS, LLC
	300 PRESTON AVE, 5TH FL
	CHARLOTTESVILLE, VA 22902
Fiscal Year:	2002
Department:
Project Start:	20-SEP-2002
Project End:	19-SEP-2003
ICD:	NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG:	ZRG1