Novel Catalytic MetalloDrug Targeting IRES RNA for Treatment of HCV Infection

描述(申请人提供)：丙型肝炎病毒对60%的慢性肝炎病例和50%的肝硬变、终末期肝病和肝癌病例负责。事实证明，有效的疫苗难以找到，聚乙二醇化干扰素的首选疗法对不到50%的1型患者和75%的2型或3型患者有效。显然，需要新的治疗方案。对作为药物靶标的丙型肝炎病毒IRES RNA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上。金属制药公司创造了一种新的平台技术(金属药物)，该技术有可能不可逆转地破坏丙型肝炎病毒IRES RNA。具体目标是在确认针对IRES RNA的细胞作用模式和摄取机制之后，为IND启用临床前测试选择主导和后备候选药物；评估PK、毒性和疗效数据；以及探索改善血清半衰期的方法。 与公共卫生相关：全世界有数百万人感染了丙型肝炎病毒，其中包括很大一部分美国人口。60%的慢性肝炎和50%的肝硬变、终末期肝病和肝癌是由丙型肝炎病毒引起的。事实证明，有效的疫苗难以找到，目前的治疗方法对不到50%的患者有效。显然，需要新的治疗替代方案。金属制药公司创造了一种新型的治疗药物(金属药物)，这种药物通过破坏病毒生命周期中的一个关键分子来发挥作用，有可能阻止病毒的发展或完全消除病毒。

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.