Novel PPAR alpha/gamma Agonist for Type 2 Diabetes

说明(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，结合PPARα/伽马激动剂。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显示了降低葡萄糖和甘油三酯的活性。第一阶段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。三种与2型糖尿病代谢紊乱相关的动物模型(高血糖、高甘油三酯血症和高血压)将被用来评估Thr-0940的药效学特征。肥胖、胰岛素抵抗的db/db小鼠将被用来评估Thr-0940的抗糖尿病效果。在这些研究中将产生重要的剂量反应数据。胰岛素抵抗、高脂血症、非糖尿病脂肪喂养的大鼠将被用来研究Thr-0940的降甘油三酯作用。胰岛素抵抗的SHR大鼠将被用来评价Thr-0940的降压活性。将与其他活性降糖和降甘油三酯药物进行比较，以衡量Thr-0940相对于现有药物的潜在优势。来自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。

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.