DISCOVERY AND DEVELOPMENT OF ISOZYME‐SELECTIVE INHIBITORS INVOLVED IN LIPID METABOLISM

• Published in: Enzyme Technologies pp. 55 - 80
• Main Authors: Ohshiro, Taichi, Tomoda, Hiroshi
• Format: Book Chapter
• Language: English
• Published: Hoboken, NJ John Wiley & Sons, Inc 30.12.2013
• Subjects: acyl‐coa: cholesterol acyltransferase (ACAT); diacylglycerol acyltransferase (DGAT); isozyme‐selective inhibitors; lipid metabolism
• ISBN: 0470286261; 9780470286265
• DOI: 10.1002/9781118739907.ch2

This chapter summarizes the methods of discovery of isozyme‐selective inhibitors of diacylglycerol acyltransferase (DGAT) and acyl‐coa: cholesterol acyltransferase (ACAT) and also describe their future prospects. Recently, two DGAT isozymes involved in lipid metabolism were identified in mammals: DGAT1 and DGAT2. DGAT inhibitors had been studied before there was understanding of the distinct functions of DGAT1 and DGAT2 isozymes. However, it is important to measure the selectivity of such inhibitors toward the isozymes. The enzyme ACAT (EC 2.3.1.26), which catalyzes the synthesis of cholesteryl ester (CE) from free cholesterol and long‐chain fatty acyl‐CoA, is considered to be a promising therapeutic target. ACAT plays important roles in mammals. Recent advances in gene technology and molecular biology have provided researchers with new strategies and methodologies for drug discovery. To date, many isozymes have been identified.