CJ-13,981 and CJ-13,982, new squalene synthase inhibitors.

作者信息

Watanabe S, Hirai H, Kambara T, Kojima Y, Nishida H, Sugiura A, Yamauchi Y, Yoshikawa N, Harwood H J, Huang L H, Kojima N

机构信息

Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc., Aichi, Japan.

出版信息

J Antibiot (Tokyo). 2001 Dec;54(12):1025-30. doi: 10.7164/antibiotics.54.1025.

Two new squalene synthase (SSase) inhibitors, CJ-13,981 (I) and CJ-13,982 (II), were isolated from the fermentation broth of an unidentified fungus CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.