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.
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.
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|Yu, Zhen; Han, Menglu; Cowan, James A (2015) Toward the design of a catalytic metallodrug: selective cleavage of G-quadruplex telomeric DNA by an anticancer copper-acridine-ATCUN complex. Angew Chem Int Ed Engl 54:1901-5|
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|Hocharoen, Lalintip; Joyner, Jeff C; Cowan, J A (2013) N- versus C-domain selectivity of catalytic inactivation of human angiotensin converting enzyme by lisinopril-coupled transition metal chelates. J Med Chem 56:9826-36|
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|Joyner, Jeff C; Keuper, Kevin D; Cowan, J A (2013) Kinetics and Mechanisms of Oxidative Cleavage of HIV RRE RNA by Rev-Coupled Transition Metal Chelates. Chem Sci 4:1707-1718|
|Joyner, Jeff C; Keuper, Kevin D; Cowan, J A (2012) DNA nuclease activity of Rev-coupled transition metal chelates. Dalton Trans 41:6567-78|
|Bradford, Seth; Cowan, J A (2012) Catalytic metallodrugs targeting HCV IRES RNA. Chem Commun (Camb) 48:3118-20|
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