Novel Catalytic MetalloDrug Targeting IRES RNA for Treatment of HCV Infection

描述（由申请人提供）：HCV是造成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。一种有效的疫苗已经被证明是难以捉摸的，首选的聚乙二醇干扰素治疗在不到50%的基因型1患者和75%的基因型2或3患者中有效。显然，需要新的治疗替代方案。HCV IRES RNA作为药物靶点的兴趣反映在越来越多的小型和大型制药公司追求这一目标。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。具体目标是在验证针对IRES RNA的细胞作用模式和摄取机制后，选择用于IND使能临床前试验的先导和备用候选药物;评估PK、毒性和疗效数据;探索改善血清半衰期的方法。 公共卫生相关性：全世界有数百万人感染HCV，包括美国人口的很大一部分。HCV是造成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。一种有效的疫苗已经被证明是难以捉摸的，目前的治疗对不到50%的患者有效。显然，需要新的治疗替代方案。MetalloPharm创造了一类新型的治疗药物（金属药物），通过破坏病毒生命周期中的关键分子来发挥作用，有可能阻止病毒的进展或完全消除病毒。

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.