NASH 临床前模型中选择性激酶抑制剂的评估-猫眼课题宝

NASH 临床前模型中选择性激酶抑制剂的评估

批准号：

10080619

负责人：

Fabio Cohen Tucci

金额：

$37.5万

依托单位：

EPIGEN BIOSCIENCES, INC.

依托单位国家：

美国

项目类别：

财政年份：

2020

资助国家：

美国

项目状态：

已结题

起止时间：

2020-09-01 至 2021-08-31

来源：

https://reporter.nih.gov/project-details/10080619

关键词：

70-kDa Ribosomal Protein S6 Kinases Affect Animal Model Area C57BL/6 Mouse Carbohydrates Cell Differentiation process Cell Proliferation Cells Chemistry Cholesterol Chronic Chronic Disease Cicatrix Cirrhosis Clinical Trials Control Groups Diet Disease Dyslipidemias Fatty acid glycerol esters Female Fibrosis Fragile X Syndrome Fructose Goals Grant Hepatic Hepatic Insufficiency Histologic Human Individual Inflammation Insulin Resistance Investigational Drugs Investigational New Drug Application Lead Literature Liver Liver Fibrosis Liver diseases Malignant neoplasm of liver Metabolic syndrome Methods Modeling Mus Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Oral Outcome Pathology Pharmaceutical Preparations Pharmacology Pharmacology Study Pharmacotherapy Phase Population Pre-Clinical Model Prevalence Process Rattus Risk Rodent Small Business Innovation Research Grant Small Business Technology Transfer Research Supplementation Testing Therapeutic Toxicology Trans Fats Wild Type Mouse Work clinical candidate clinical development effective therapy epigen feeding human disease in vivo inhibitor/antagonist kinase inhibitor macrophage male mortality mouse model non-alcoholic fatty liver disease nonalcoholic steatohepatitis novel novel therapeutics preclinical evaluation programs scale up small molecule

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Summary The ultimate goal of this application is to develop one of Epigen’s proprietary, selective and drug-like kinase inhibitors for the effective treatment of liver fibrosis associated with chronic diseases such as non-alcoholic steatohepatitis (NASH), a severe type of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disease and is associated with obesity and type-2 diabetes. There are no effective treatments available for NASH. Our approach will involve the pre-clinical evaluation of one advanced lead compound, identified according to a disease-specific progressive cutoff criteria, in two animal models of NASH to establish the proof-of-concept in this indication. The successful outcome of this work will enable initiation of efforts to establish a more detailed understanding of the pharmacology of the most promising candidate in rodent NASH models and commencement of toxicology and chemistry, manufacturing and controls (CMC) work to support filing of an investigational new drug (IND) application and eventually initiation of clinical trials in humans.

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