TREATMENT OF ARTHRITIS WITH AN ADENOSINE-3 AGONIST

描述（改编自申请人摘要）：本提案描述了 腺苷3激动剂的新原理的开发 受体具有广泛的抗炎潜力。该提案提供了证据， 腺苷3（A3）受体的激动剂，即 N6-（3-碘苄基）-腺苷-5 '-N-甲基脲酰胺（IB-MECA）;（1）减少 多种促炎细胞因子和趋化因子的产生;（2）增强 抗炎细胞因子IL-10的产生;（3）抑制 诱导型一氧化氮合酶亚型的表达，以及（4）保护 在啮齿动物关节炎模型中。本提案的具体目标是 探讨口服IB-MECA对啮齿类动物关节炎的疗效 模型，并获得该A3受体激动剂的初步毒性数据。 II期研究将集中在额外的临床前药物测试 以支持人体临床试验的监管备案。 拟议商业应用：不可用

DESCRIPTION (Adapted from the applicant's abstract): This proposal describes the development of the novel principle that agonists of the adenosine 3 receptor have broad anti-inflammatory potential. The proposal presents evidence that an agonist of the adenosine 3 (A3) receptor, namely N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA); (1) reduces the production of multiple pro-inflammatory cytokines and chemokines; (2) enhances the production of the anti-inflammatory cytokine IL-10; (3) inhibits the expression of the inducible isoform of nitric oxide synthase and (4) protects in rodent models of arthritis. The specific aims of the current proposal are to explore the efficacy of orally administered IB-MECA in the rodent arthritis model and to obtain preliminary toxicity data of this A3 receptor agonist. Phase II studies will focus on additional pre-clinical pharmaceutical testing to support a regulatory filing for human clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE