Multiple strategies for the preparation of a sulfur-35 labeled NPC1L1 radioligand

During our effort to design a receptor binding assay to aid in the elucidation of the molecular mechanism of ezetimibe, we prepared a sulfur-35 containing radioligand which exhibits improved potency over the glucuronide conjugate of ezetimibe in both native enterocyte brush border membranes and membranes from cells expressing recombinant NPC1L1. Herein, we describe the different synthetic strategies which were used to obtain this compound as well as its effectiveness in the aforementioned assay.

The discovery of a sulfur-35 labeled radioligand with high affinity for the NPC1L1 receptor across species is reported.Figure optionsDownload as PowerPoint slide