Hepatic

In vitro and mouse studies identified a peripherally restricted purine-based CNR1 antagonist that could help treat alcoholic liver steatosis. Chemical synthesis of analogs of the CNR1 antagonist otenabant and in vitro binding assays yielded a peripherally restricted purine-based compound that bound human CNR1 with a K_i of 8 nM. In a mouse model of alcoholic liver steatosis, the compound decreased lipid levels in the liver compared with vehicle. In healthy mice, the compound had a brain-to-plasma ratio of 0.03 when administered orally. Next steps by RTI International could include testing the compound in additional models of alcoholic liver steatosis.

In 2008, Pfizer Inc. discontinued Phase III testing of otenabant for obesity...