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ImQuest Life Sciences lead product for development as a new and novel drug for the treatment of patients infected with HIV is the pyrimidinedione IQP-0410 (formerly known as SJ-3366). This small molecule inhibitor of HIV uniquely targets two steps in HIV replication including reverse transcription and virus entry. SAR evaluations have demonstrated that the molecular features of the pyrimidinediones responsible for the two distinct mechanisms of action are integrated in the structure of the molecule and substituents required for RT inhibition versus entry inhibition are not distinct but overlapping. Inhibition of RT is specific for HIV-1 with efficacy at sub-nanomolar concentration levels. Inhibition of entry occurs by a mechanism involving recognition of a conformational epitope formed upon interaction of the virus with the target cell and the drug target forms following interaction of the viral receptors with CD4 and the chemokine receptors but prior to fusion of the viral and cellular membranes. Entry inhibition against clinical strains of virus occurs at nanomolar concentration levels and the range of action includes both HIV-1 and HIV-2.
At present, preclinical virology on IQP-0410 has been completed and initial preclinical pharmacology and toxicology studies are in progress. Initial acute toxicology studies in rats have demonstrated no dose limiting toxicity up to 2000 mg/kg/day. It is expected that all pharmacology/toxicology studies will be completed in 2007 and an IND will be submitted to the FDA to initiate human clinical trials. |
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