Novel Catalytic MetalloDrug Targeting IRES RNA for Treatment of HCV Infection

靶向 IRES RNA 的新型催化金属药物治疗 HCV 感染

基本信息

批准号：
8062756
负责人：
Ada S Cowan
金额：
$ 84.4万
依托单位：
METALLOPHARM, LLC
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8062756
关键词：
Advanced Development Adverse effects American Back Binding Biodistribution Biological Assay Biological Models Blood Cessation of life Chemistry Chronic Hepatitis Chronic Hepatitis C Cirrhosis Clinical Data Communicable Diseases Complement Data Development Dose Drug Delivery Systems Drug Design Funding Genotype Goals Half-Life Hepatitis C Hepatitis C virus In Vitro Infection Innovative Therapy Interferons Lead Life Life Cycle Stages Liver diseases Malignant neoplasm of liver Medical Metals Methods Mutation Oral Outcome Patients Peptide Hydrolases Pharmaceutical Preparations Phase Plasma Polymerase Population Preparation RNA Replicon Serum Site Staging System Technology Testing Therapeutic Time Toxic effect Toxicology Translations Vaccines Validation Viral Virus alternative treatment anti-hepatitis C base drug candidate drug development drug discovery effective therapy improved in vivo indexing inhibitor/antagonist interest interferon therapy novel novel strategies peptidomimetics phase 2 study pre-clinical prevent research clinical testing stem uptake viral RNA

项目摘要

DESCRIPTION (provided by applicant): HCV is responsible for 60% of the cases of chronic hepatitis and 50% of cases of cirrhosis, end- stage liver disease, and liver cancer. An effective vaccine has proved elusive and the preferred therapy with pegylated interferon is effective in less than 50% of patients with genotype 1 and 75% of patients with genotypes 2 or 3. Clearly, new treatment alternatives are needed. Interest in HCV IRES RNA as a drug target is reflected by the increasing number of small and large pharma companies pursuing that goal. MetalloPharm has created a novel platform technology (metallodrugs) that has the potential to irreversibly destroy the HCV IRES RNA. The specific aims are directed toward selection of a lead and back-up drug candidate for IND-enabling pre- clinical testing following validation of cellular mode of action against IRES RNA and uptake mechanisms; assessment of PK, toxicity and efficacy data; and exploration of methods to improve serum half life. PUBLIC HEALTH RELEVANCE: Millions of people worldwide are infected with HCV, including a significant portion of the US population. HCV is responsible for 60% of the cases of chronic hepatitis and 50% of cases of cirrhosis, end-stage liver disease, and liver cancer. An effective vaccine has proved elusive and current therapy is effective in less than 50% of patients. Clearly, new treatment alternatives are needed. MetalloPharm has created a novel class of therapeutics (metallodrugs) that function by destroying a key molecule in the viral life cycle with the potential to halt the progression of, or completely eliminate the virus.

描述（由申请人提供）：HCV造成60％的慢性肝炎病例和50％的肝硬化病例，末期肝病和肝癌。事实证明，一种有效的疫苗难以捉摸，使用叶甲状干扰素的首选治疗在不到50％的基因型1和75％的基因型2或3患者中有效。显然，需要新的治疗替代方法。对HCV IRES RNA作为药物目标的兴趣反映了越来越多的小型制药公司追求该目标的大型制药公司。金属载体创造了一种新颖的平台技术（冶金），该技术有可能不可逆地破坏HCV IRES RNA。具体目的是针对选择铅和备用药物候选药物，用于在验证针对IRES RNA和摄取机制的细胞作用模式后，进行临床测试。评估PK，毒性和功效数据；以及探索改善血清半衰期的方法。公共卫生相关性：全世界数百万的人感染了HCV，其中包括美国人口的很大一部分。 HCV负责60％的慢性肝炎病例和50％的肝硬化病例，末期肝病和肝癌。有效的疫苗已证明难以捉摸，目前的治疗在不到50％的患者中有效。显然，需要新的治疗方法。金属植物创造了一种新型的治疗剂（金属果），通过破坏病毒生命周期中的关键分子来起作用，并可能阻止或完全消除病毒的进展。