OXIDOSQUALENE CYCLASE AS A PROTEIN TARGET FOR ANTICANCER THERAPEUTICS

摘要

The present invention identifies the cholesterol biosynthetic pathway, including the enzyme oxidosqualene cyclase, as new protein targets for anti-tumor therapeutics. The present invention further provides a class of oxidosqualene cyclase inhibitors containing a tertiary amine linked with aromatic ring structures, as a new class of anticancer agents. Compounds disclosed herein have been tested in 19 cell lines including breast cancer, prostate cancer, lung cancer (including drug-resistant lung cancer H69AR), colon cancer, ovarian cancer (including drug-resistant OVCAR-3), and pancreatic cancer cells, as wells as in human breast and prostate xenograft tumor growth in nude mice, and have been shown to be active.