CJ-13,981 and CJ-13,982, New Squalene Synthase Inhibitors

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 CL15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 μM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 μM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3, 4-dicarboxy15-hexadecenoic acid and 3-hydroxy-3, 4-dicarboxyhexadecanoic acid, respectively.