A Carboxylic Acid Isostere Screen of the DHODH Inhibitor Brequinar
Bioorganic & medicinal chemistry letters(2020)
摘要
Dihydroorotate dehydrogenase (DHODH) enzymatic activity impacts many aspects critical to cell proliferation and survival. Recently, DHODH has been identified as a target for acute myeloid differentiation therapy. In preclinical models of AML, the DHODH inhibitor Brequinar (BRQ) demonstrated potent anti-leukemic activity. Herein we describe a carboxylic acid isostere study of Brequinar which revealed a more potent non-carboxylic acid derivative with improved cellular potency and good pharmacokinetic properties.
更多查看译文
关键词
Dihydroorotate dehydrogenase,Acute myeloid leukemia,Brequinar,Inhibitor
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要