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

SHUZO WATANABE; HIDEO HIRAI; TAKAHITO KAMBARA; YASUHIRO KOJIMA; HIROYUKI NLSHIDA; AYUMU SUGIURA; YUJI YAMAUCHI; NOBUJI YOSHIKAWA; H. JAMES HARWOOD; LIANG HSIUNG HUANG; NAKAO KOJIMA

doi:10.7164/antibiotics.54.1025

SHUZO WATANABE, HIDEO HIRAI, TAKAHITO KAMBARA, YASUHIRO KOJIMA, HIROYUKI NLSHIDA, AYUMU SUGIURA, YUJI YAMAUCHI, NOBUJI YOSHIKAWA, H. JAMES HARWOOD, LIANG HSIUNG HUANG, NAKAO KOJIMA

Author information

SHUZO WATANABE
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
HIDEO HIRAI
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
TAKAHITO KAMBARA
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
YASUHIRO KOJIMA
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
HIROYUKI NLSHIDA
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
AYUMU SUGIURA
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
YUJI YAMAUCHI
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
NOBUJI YOSHIKAWA
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc.
H. JAMES HARWOOD
PGRD, Groton Laboratories, Pfizer Inc.
LIANG HSIUNG HUANG
PGRD, Groton Laboratories, Pfizer Inc.
NAKAO KOJIMA
Faculty of Pharmacy, Meijo University

JOURNAL FREE ACCESS

2001 Volume 54 Issue 12 Pages 1025-1030

DOI https://doi.org/10.7164/antibiotics.54.1025

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Abstract

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.

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