Prediction of Clinically Relevant Herb-Drug Clearance Interactions Using Sandwich-Cultured Human Hepatocytes: Case Study.

The Schisandraceae family is reported to have a range of pharmacological activities, including anti-inflammatory effects. As with all herbal preparations, extracts of species are mixtures composed of >50 lignans, especially schizandrins, deoxyschizandrins, and gomisins. In China, extract (SSE) is often coadministered with immunosuppressant treatment of transplant recipients.

Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development.