Novel Catalytic MetalloDrug Targeting IRES RNA for Treatment of HCV Infection

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。

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.