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Several members of the pyrimidinedione series of anti-HIV agents are being evaluated for potential microbicidal use to prevent the sexual transmission of HIV and other infectious organisms. The pyrimidinediones inhibit HIV at two steps of replication, including virus entry and reverse transcription. Since both of these steps occur before the integration of the viral provirus into the target cells, both antiviral mechanisms are highly appropriate for a microbicide. The significant potency of the pyrimidinediones (efficacy in the sub-nanomolar concentration range) as well as the fact that they could easily be used in combination with a second microbicide to yield a two-drug therapy targeting three steps in HIV replication is highly exciting from the development perspective. ImQuest has completed all of the preclinical virology for twelve members of the pyrimidinedione series as potential microbicides and we have identified three highly potent molecules with superior microbicidal properties. Our development of these three molecules now involves evaluation of the agents in combination with other potential microbicides.
ImQuest is currently developing our topical microbicide portfolio as single and combination agents with funding from the NIH. ImQuest is also working in collaborative ways with various organizations involved in microbicide research to facilitate the development of our microbicidal compounds. ImQuest anticipates that our most potent microbicide as well as a rationale combination of microbicides will be submitted for IND and clinical trial in 2007. |
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