A2a Adenosine Agonists for Diabetic Nephropathy

A2a 腺苷激动剂治疗糖尿病肾病

• 批准号: 6994248
• 负责人: ROBERT D THOMPSON
• 金额: $ 14.73万
• 依托单位: ADENOSINE THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6994248
• 关键词: chemoprevention; diabetes mellitus therapy; diabetic nephropathy; disease /disorder model; drug design /synthesis /production; drug screening /evaluation; injection /infusion; kidney disorder chemotherapy; laboratory rat; nonhuman therapy evaluation; pharmacokinetics; purinergic receptor; stimulant /agonist; chemoprevention; diabetes mellitus therapy; diabetic nephropathy; disease /disorder model; drug design /synthesis /production; drug screening /evaluation; injection /infusion; kidney disorder chemotherapy; laboratory rat; nonhuman therapy evaluation; pharmacokinetics; purinergic receptor; stimulant /agonist

DESCRIPTION (provided by applicant): Diabetic nephropathy (DN) accounts for approximately 40% of the cases of renal failure requiring dialysis or transplantation. Moreover, diabetic nephropathy is associated with markedly higher morbidity and mortality rates. It is important to develop novel interventions to prevent complications of diabetes. Inflammation in the genesis of diabetes, as well as its complications, is considered an important pathogenic mechanism. Adenosine 2A receptors (A2ARs) are expressed in kidney as well as bone marrow derived cells and we have previously shown that upon activation A2A Rs reduces inflammation when administered acutely. Our preliminary data demonstrate that A2A R agonists have profound effects to reduce renal injury when infused chronically in a rat model of streptozotocin (STZ)-induced diabetic nephropathy. Adenosine Therapeutics, LLC has recently developed ATL313, a novel, orally active A2A R agonist. The 1st Aim of this Phase 1 application is to examine the pharmacokinetics, oral bioavailability and initial toxicology of ATL313. The 2nd Aim is to demonstrate the proof of principle that ATL313 is effective in primary and secondary prevention of diabetic nephropathy. ATL313 will be administered via osmotic mini-pumps to establish its efficacy. This will prepare us for the Phase 2 goal of further testing of the compound through oral administration.

描述（由申请人提供）：糖尿病性肾病（DN）约占需要透析或移植的肾衰竭病例的40％。此外，糖尿病性肾病与发病率和死亡率明显更高有关。制定新的干预措施以防止糖尿病并发症。糖尿病起源及其并发症的炎症被认为是一种重要的致病机制。腺苷2A受体（A2AR）在肾脏和骨髓衍生的细胞中表达，我们先前已经表明，激活后A2A RS急性施用后会减少炎症。我们的初步数据表明，在慢性链蛋白酶（STZ）诱导的糖尿病性肾病大鼠模型中慢性注入时，A2A R激动剂对减少肾脏损伤具有深远的作用。 Adenosine Therapeutics，LLC最近开发了ATL313，这是一种新型的口服A2A R激动剂。该第1阶段应用的第一个目的是检查ATL313的药代动力学，口服生物利用度和初始毒理学。第二个目的是证明ATL313在糖尿病性肾病的原发和次要预防中有效的原理证明。 ATL313将通过渗透迷你泵进行管理以确立其功效。这将使我们为通过口服给药进一步测试该化合物的第二阶段目标做好准备。