Pre-con Workshop | Day 1 | Day 2 | Download Brochure
TUESDAY, APRIL 29
8:00 am Breakout Group Discussions: Meet the Experts
Brainstorming discussion groups moderated by experts in the area. Attendees are invited to choose the topic according to their main interest; however, they may switch between groups. We emphasize that this discussion is for an interactive informal exchange among scientists and is not meant to be, in any way, a corporate or product discussion.
OTHER MECHANISMS
9:00 Chairperson’s Remarks
A. Donny Strosberg, Ph.D., Professor, Department of Infectology, The Scripps Research Institute-Florida
9:05 Protein-Protein Interactions in HCV as New Targets for Drug Discovery
A. Donny Strosberg, Ph.D., Professor, Department of Infectology, The Scripps Research Institute-Florida
Homo-dimerization of HCV core protein is essential for assembly of the viral nucleocapsid. We have designed assays to monitor this protein-protein interaction. Using both HTRF and Alpha formats we have identified a 15-residue core-derived peptide which inhibits dimerization of a 106 residue fragment of core, (IC50=22 micromolar) and blocks infectious HCV release from host hepatoma cells. Modified versions of this peptide may serve as high-affinity inhibitors of HCV. Additionally, non-peptidic inhibitors identified in large libraries of chemical compounds using our assays will also be evaluated for their effect on the propagation of infectious HCV.
9:35 Taribavirin: Discovery and Development of 2nd Generation of Ribavirin for Treatment of HCV Infection
Jim Z. Wu, Ph.D., Director, Preclinical and Translational Research, Global Drug Development, Valeant Pharmaceuticals International
Ribavirin is the only approved small-molecule antiviral drug that is active against both DNA and RNA viruses. However, it can cause dose-limiting anemia in about 20% of treated patients. Taribavirin (previously known as viramidine) is a pyrimidine nucleoside analog and a pro-drug of ribavirin. It has shown a lower incidence of anemia in clinical trials. This presentation will cover the history of discovery and development of taribavirin focusing on its mechanism of action studies. The current development activities and future prospective of taribavirin will be discussed.
10:05 Technology Watch (Sponsorship Available)
10:20 Networking Coffee Break, Poster and Exhibit Viewing
11:00 Targeting HCV NS4b Function: A New Approach to Anti-HCV Activity
Christopher Roberts, Ph.D., Senior Director, Medicinal Chemistry, Genelabs Technologies, Inc.
Considerable effort in the industry has resulted in multiple compounds directed against the HCV viral protease and polymerase enzymes. However, agents with novel mechanisms of action are needed to combat the threat of emerging viral resistance. We have identified a series of potent compounds from an HCV replicon cell-based high-throughput screen which showed no activity against the isolated protease or polymerase enzymes. Resistance screening with selected compounds identified mutated amino acid changes in a well-defined region of NS4b that were subsequently confirmed to decrease compound potency in a transient HCV replicon assay. Initial optimization has led to multiple series of compounds. The most promising display replicon potency under 50 nM, equivalent activity against both genotypes 1a and 1b, a promising pharmacokinetic profile, and antiviral activity in combination with agents currently approved or under clinical development. We will describe the biological characterization of these compounds.
11:30 Developing First-in-Class HCV Drugs Targeting Viral Entry
Flossie Wong-Staal, Ph.D., CSO, Executive Vice President Research, ItherX Pharmaceuticals, Inc.
At ItherX, we are developing entry inhibitors for HCV infection. We utilized HIV env-deleted vectors pseudotyped with HCV E1-E2 envelope proteins from different genotypes (HCVpp) as a surrogate system for drug screening, and infectious HCV (genotype 2a) for hit confirmation. We have identified three series of chemical compounds that inhibit HCV at nanomolar IC50 and > 1000-fold therapeutic window. One of these series was found to specifically bind to HCV E1-E2. The lead compounds of Series 1 are in preclinical development, with a target IND date in Q4/2008.
12:00 pm Close of HCV Drug Discovery Conference
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