CP - 225,917和CP - 263,114，来自一种未鉴定真菌的新型Ras法尼基化抑制剂。I. 分类学、发酵、分离及生化特性

CP-225,917 and CP-263,114, novel Ras farnesylation inhibitors from an unidentified fungus. I. Taxonomy, fermentation, isolation, and biochemical properties.

作者信息

Dabrah T T, Harwood H J, Huang L H, Jankovich N D, Kaneko T, Li J C, Lindsey S, Moshier P M, Subashi T A, Therrien M, Watts P C

机构信息

Pfizer Central Research, Groton, CT 06340, USA.

出版信息

J Antibiot (Tokyo). 1997 Jan;50(1):1-7. doi: 10.7164/antibiotics.50.1.

DOI:10.7164/antibiotics.50.1

PMID:9066758

Abstract

During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 microM and 20 microM, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 microM and CP-263,114 with an IC50 of 160 microM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.

摘要

在我们筛选角鲨烯合酶抑制剂和Ras法尼基化抑制剂的过程中，发现一种新型真菌培养物能产生两种结构独特的化合物CP - 225,917和CP - 263,114，以及扎戈司酸A（角鲨素I）。这两种化合物均以双环[4.3.1]癸-1, 6 - 二烯核心加两条延长的烷基链为特征。CP - 225,917和CP - 263,114对大鼠脑Ras法尼基转移酶的抑制IC50值分别为6微摩尔和20微摩尔。CP - 225,917对角鲨烯合酶的抑制IC50值为43微摩尔，CP - 263,114的IC50为160微摩尔。该产生菌虽未完全分类，但具有不育茎点霉属物种的特征。