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

• 批准号: 8270019
• 负责人: Ada S Cowan
• 金额: $ 81.3万
• 依托单位: METALLOPHARM, LLC
• 依托单位国家: 美国
• 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/8270019
• 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

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.

描述（由申请人提供）：HCV是60%的慢性肝炎病例和50%的肝硬化、终末期肝病和肝癌病例的原因。一种有效的疫苗已被证明是难以找到的，聚乙二醇化干扰素的首选治疗方法对不到50%的基因型1患者和75%的基因型2或3患者有效。显然，我们需要新的治疗方案。越来越多的小型和大型制药公司追求这一目标，反映了对HCV IRES RNA作为药物靶点的兴趣。MetalloPharm创造了一种新的平台技术（金属药物），具有不可逆地破坏HCV IRES RNA的潜力。具体目标是在对IRES RNA的细胞作用方式和摄取机制进行验证后，选择一种先导和后备候选药物进行ind临床前测试；PK、毒性和药效数据评估；探讨提高血清半衰期的方法。