A2A Adenosine Receptor Agonist for the Treatment of IBD

A2A 腺苷受体激动剂治疗 IBD

• 批准号: 6741790
• 负责人: ROBERT D THOMPSON
• 金额: $ 33.74万
• 依托单位: ADENOSINE THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741790
• 关键词: SCID mouse; dosage; drug design /synthesis /production; drug screening /evaluation; enzyme linked immunosorbent assay; flow cytometry; gastrointestinal disorder chemotherapy; histology; inflammatory bowel diseases; laboratory mouse; liquid chromatography mass spectrometry; neurotransmitter agonist; nonhuman therapy evaluation; oral administration; pharmacokinetics; purinergic receptor; statistics /biometry; therapy design /development; tissue /cell culture

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.

简介（由申请人提供）：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拥有一系列强效和高选择性A2A腺苷受体激动剂的配方和使用专利。其中一种化合物ATL146e是冠状动脉血管扩张剂，已被开发（在SBIR资助的帮助下）作为冠状动脉显像剂，已被Bristol Meyers Squibb授权专门用于冠状动脉疾病的药物显像，目前正处于I期临床试验。ATL146e和其他A2A腺苷受体激动剂在远低于血管活性剂量的情况下对骨髓源性细胞发挥强大的抗炎作用。弗吉尼亚大学（UVa）的Fabio Cominelli博士和他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，ATL146e对溃疡性结肠炎引起的炎症和损伤具有深远的保护作用。这是ATL和UVa提出的一项sbur - at I期申请，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小鼠模型中进行测试，该模型已由Cominelli实验室进行了很好的表征。目的是：(1)优化给药时机；(2)确定ATL146e是否能延缓疾病症状的发作；(3)描述第二代口服活性化合物的特征；(4)合成新的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。目前迫切需要改进IBD的治疗方法。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，并在四年内开发第二代化合物。