A2A Adenosine Receptor Agonist for the Treatment of IBD

描述(由申请人提供)：腺苷治疗有限责任公司(ATL)是一家生物技术公司，成立于1999年，弗吉尼亚州夏洛茨维尔。ATL拥有一系列有效和高选择性的A2A腺苷受体激动剂的配方和使用专利。其中一种化合物ATL146e是一种冠状动脉血管扩张剂，(在SBIR资金的帮助下)已被开发为冠状动脉显像剂，已被批准给Bristol Meyers Squibb专门用于冠状动脉疾病的药理成像，目前正处于I期临床试验。ATL146e和其他A2A腺苷受体激动剂通过对骨髓来源细胞的作用发挥强大的抗炎作用，剂量远远低于血管活性。法比奥·科米内利博士和他在弗吉尼亚大学(UVA)的同事是炎症性肠病(IBD)研究方面的专家。他们在兔模型中发现，ATL146e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提出的SBIR-AT第一阶段提案，目的是开发ATL146e和第二代口服活性化合物作为治疗IBD的新疗法。这一概念将在相关的IBD小鼠模型上进行测试，该模型已经由Cominelli实验室很好地描述了特征。其目的是：(1)优化药物剂量和时机；(2)确定ATL146e是否可以延缓疾病症状的出现；(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；(5)确定候选药物的化学性质、药代动力学和生物分布。IBD的治疗方法亟需改进。我们的目标是在两年内开始一种治疗IBD的新药的临床试验，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.