The enzyme sterol O-acyltransferase (SOAT, also known as acyl-CoA:cholesterol acyltransferase (ACAT)), an endoplasmic reticulum membrane protein, has important roles in cholesterol regulation in humans.1 SOAT is expected to be a promising target for the development of new anti-atherosclerotic agents. Pharmaceutical laboratories have reported a number of synthetic SOAT inhibitors; however, none have been successfully developed to date because of their associated side effects or low/no efficacy in clinical trials.2, 3 Recent molecular biological studies revealed the existence of two SOAT isozymes, SOAT1 and SOAT2, with distinct functions. SOAT1 is ubiquitously expressed in all tissues and cells, while SOAT2 is expressed predominantly in the liver (hepatocytes) and small intestine.1, 4 Therefore, it is important to determine the selectivities of inhibitors to the two SOAT isozymes for their development as new anti-atherosclerotic reagents.2, 3 Our group has extensive experience of discovering SOAT inhibitors of microbial origins using an enzyme assay with rat liver microsomes.5 After the discovery of two SOAT isozymes, we established cell-based and enzyme assays utilizing Chinese hamster ovary (CHO) cells expressing African green monkey SOAT1 (SOAT1-CHO cells) and SOAT2 (SOAT2-CHO cells).6 In the two assays, the IC50 values of a compound were measured to calculate the selectivity index (SI, log [IC50 for SOAT1]/[IC50 for SOAT2]). We defined compounds into three types of SOAT inhibitors from the SI values; dual-type inhibitors with −1.00SI+1.00, SOAT1-selective inhibitors with SI<−1.00 and SOAT2-selective inhibitors with +1.00