A2A Adenosine Receptor Agonist for the Treatment of IBD

Adenosine Therapeutics，LLC（ATL）是一家生物技术公司，于1999年在弗吉尼亚州夏洛茨维尔成立。ATL拥有A2 A腺苷受体强效和高选择性激动剂家族的配方和使用专利。其中一种化合物ATL 146 e是一种冠状血管扩张剂，并已被开发（在SBIR资助的帮助下）为冠状动脉成像剂，已被授权给布里斯托迈耶斯施贵宝公司专门用于冠状动脉疾病的药理学成像，目前正处于I期临床试验中。ATL 146 e和其他A2 A腺苷受体激动剂通过在远低于血管活性剂量的剂量下作用于骨髓源性细胞而发挥强大的抗炎作用。Fabio Cominelli博士和他在弗吉尼亚大学（UVa）的同事是研究炎症性肠病（IBD）的专家。他们在兔子模型中发现，ATL 146 e对溃疡性结肠炎引起的炎症和损伤具有深刻的保护作用。这是ATL和UVa的SBIR-AT I期提案，目的是开发ATL 146 e和第二代口服活性化合物作为治疗IBD的新疗法。这一概念将在Cominelli实验室已充分表征的IBD相关小鼠模型中进行测试。其目标是：（1）优化药物剂量和时间;（2）确定ATL 146 e是否可以延迟疾病症状的发作;（3）表征第二代口服活性化合物;（4）合成新化合物和放射性类似物;以及（5）确定候选药物的化学性质、药代动力学和生物分布。非常需要改善IBD的疗法。我们的目标是在两年内开始治疗IBD的新药临床试验，并在四年内开发出第二代化合物。

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.