Novel PPAR alpha/gamma Agonist for Type 2 Diabetes

治疗 2 型糖尿病的新型 PPAR α/γ 激动剂

• 批准号: 6880330
• 负责人: EDWARD P AMENTO
• 金额: $ 10万
• 依托单位: THERACOS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6880330
• 关键词: antihypertensive agents; drug screening /evaluation; hyperglycinemia; hyperlipidemia; hypertension; hypertriglyceridemia; hypoglycemic agents; insulin sensitivity /resistance; laboratory mouse; noninsulin dependent diabetes mellitus; peroxisome proliferator activated receptor; pharmacokinetics; rosiglitazone; spontaneous hypertensive rat; triglycerides

DESCRIPTION (provided by applicant): An orally active antidiabetic agent, THR-0940 is a non-thiazolidinedione, combined PPARalpha/gamma agonist. In preliminary experiments, THR-0940 demonstrated both glucose and triglyceride lowering activity in rodent models of diabetes and insulin resistance. The Phase I research plan is designed to further characterize the antidiabetic, triglyceride lowering, and antihypertensive activities of THR-0940. Three animal models that are relevant to the metabolic disturbances in type 2 diabetes (hyperglycemia, hypertriglyceridemia, and hypertension) will be used to evaluate the pharmacodynamic profile of THR-0940. Obese, insulin-resistant db/db mice will be used to evaluate the antidiabetic effect of THR-0940. Important dose response data will be generated in these studies. Insulin-resistant, hyperlipidemic, non-diabetic fat-fed rats will be used to investigate the triglyceride lowering effect of THR-0940. Insulin-resistant SHR rats will be used to evaluate the antihypertensive activity of THR-0940. Comparisons with other active antidiabetic and triglyceride lowering drugs will be made as a measure to gauge a potential advantage of THR-0940 over currently available drugs. Data from these studies will further characterize the potential of THR-0940 for treatment of type 2 diabetes and will provide valuable information to qualify this molecule for entry into clinical development.

描述（由申请人提供）：THR-0940 是一种口服活性抗糖尿病药，是一种非噻唑烷二酮类 PPARα/γ 组合激动剂。在初步实验中，THR-0940 在糖尿病和胰岛素抵抗的啮齿动物模型中表现出降低葡萄糖和甘油三酯的活性。 I 期研究计划旨在进一步表征 THR-0940 的抗糖尿病、降低甘油三酯和抗高血压活性。与 2 型糖尿病代谢紊乱（高血糖、高甘油三酯血症和高血压）相关的三种动物模型将用于评估 THR-0940 的药效学特征。肥胖、胰岛素抵抗的 db/db 小鼠将用于评估 THR-0940 的抗糖尿病作用。这些研究将产生重要的剂量反应数据。将使用胰岛素抵抗、高脂血症、非糖尿病脂肪喂养的大鼠来研究 THR-0940 的甘油三酯降低作用。胰岛素抵抗 SHR 大鼠将用于评估 THR-0940 的抗高血压活性。将与其他活性抗糖尿病和降低甘油三酯药物进行比较，作为衡量 THR-0940 相对于现有药物的潜在优势的措施。这些研究的数据将进一步表征 THR-0940 治疗 2 型糖尿病的潜力，并将提供有价值的信息，使该分子有资格进入临床开发。