Development of novel agents for the treatment of renal fibrosis

开发治疗肾纤维化的新型药物

• 批准号: 8917935
• 负责人: Michael J. Caplan
• 金额: $ 83.53万
• 依托单位: EPIGEN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8917935
• 关键词: Achievement; Acute; Animal Model; Area; Back; Behavior; Biological Assay; CYP2D6 gene; CYP3A4 gene; Caco-2 Cells; Canis familiaris; Cell model; Characteristics; Chronic Kidney Failure; Clinical; Development; Diabetic Nephropathy; Disease model; Dose; Drug Kinetics; End stage renal failure; Evaluation; Feasibility Studies; Fibrosis; Goals; Grant; Health; Human; In Vitro; Inhibitory Concentration 50; Kidney; Lead; Letters; Liver Microsomes; Lysophosphatidic Acid Receptors; Medical; Metabolic; Modeling; Mus; Oral Administration; Permeability; Pharmaceutical Preparations; Pharmacotherapy; Phase; Positioning Attribute; Preparation; Property; Rattus; Renal Replacement Therapy; Research; Safety; Selection Criteria; Series; Signal Pathway; Small Business Innovation Research Grant; Streptozocin; Testing; Therapeutic Intervention; Toxic effect; Ureteral obstruction; analog; clinical efficacy; commercialization; improved; in vivo; lead series; lipophilicity; meetings; mortality; novel; novel therapeutics; pre-clinical; preclinical study; prevent; programs; safety study; scale up; small molecule; standard of care; therapy development

DESCRIPTION (provided by applicant): The ultimate goal of our project is to develop novel therapeutics effective in chronic kidney diseases that normally develop fibrosis, lead to end stage renal disease and require renal replacement therapy. This SBIR phase 2 application builds on the results obtained in phase 1 where novel and selective small molecule antagonists were discovered that prevent the progression of renal fibrosis in a unilateral ureteral obstruction (UUO) animal model. Leads identified in phase 1 will be optimized for drug-like and ADME properties. Candidate compounds meeting the selection criteria will be assessed for safety in vivo and the best compound will be examined in several different animal models of chronic kidney disease to delineate a development path in the clinical setting.

描述（由申请人提供）：我们项目的最终目标是开发对慢性肾脏疾病有效的新型疗法，这些疾病通常会发展为纤维化，导致终末期肾脏疾病并需要肾脏替代治疗。该 SBIR 2 期应用建立在 1 期获得的结果的基础上，其中发现了新型选择性小分子拮抗剂，可以预防单侧输尿管梗阻中肾纤维化的进展 （UUO）动物模型。第一阶段确定的先导化合物将针对类药和 ADME 特性进行优化。将评估符合选择标准的候选化合物的体内安全性，并将在几种不同的慢性肾病动物模型中检查最佳化合物，以描绘临床环境中的开发路径。