oc-144-093 and Epilepsy

oc-144-093 has been researched along with Epilepsy* in 1 studies

Reviews

1 review(s) available for oc-144-093 and Epilepsy

ArticleYear
OC144-093, a novel P glycoprotein inhibitor for the enhancement of anti-epileptic therapy.
    Novartis Foundation symposium, 2002, Volume: 243

    Inhibitors of P gLycoprotein (Pgp) may be useful for the enhancement of blood-brain barrier penetration of anti-epileptic drugs (AEDs). Due to polypharmacy and the need for chronic treatment, Pgp inhibitors used in epilepsy should be highly specific and non-toxic. In particular, it may be essential to use compounds that produce minimal inhibition of enzymes involved in metabolism of AEDs and other drugs used by epilepsy patients. OC144-093 is a novel substituted diarylimidazole generated using the OntoBLOCK system, a solid-phase combinatorial chemistry technology, in combination with high-throughput cell-based screening. The compound is an extremely potent inhibitor of Pgp-mediated multidrug resistance (MDR) in cancer with an average FC50 of 32 nM, but does not inhibit multidrug resistance-associated protein (MRP1). OC144-093 is the least non-specifically toxic Pgp inhibitor described to date, with an average cytostatic IC50 of >60 microM in 15 cell types. It is not metabolized by cytochrome P450s CYP3A4, 2C8 or 2C9 enzymes involved in AED metabolism. OC144-093 does not produce a pharmacokinetic (PK) interaction with paclitaxel and has exhibited an excellent PK and safety profile in phase I clinical trials. Our results suggest that OC144-093 may represent an ideal candidate for use in enhancement of AED blood-brain barrier penetration.

    Topics: Animals; Anticonvulsants; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood-Brain Barrier; Clinical Trials, Phase I as Topic; Combinatorial Chemistry Techniques; Dogs; Drug Design; Drug Evaluation, Preclinical; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Enzyme Inhibitors; Epilepsy; Female; Humans; Imidazoles; Male; Molecular Structure; Neoplasm Proteins; Nerve Tissue Proteins; Rats; Tumor Cells, Cultured

2002
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