CP-225, 917 and CP-263, 114, Novel Ras Farnesylation Inhibitors from an Unidentified Fungus I. Taxonomy, Fermentation, Isolation, and Biochemical Properties

THOMAS T. DABRAH; H. JAMES HARWOOD; LIANG H. HUANG; NANCY D. JANKOVICH; TAKUSHI KANEKO; JIAN-CHENG LI; SARALYN LINDSEY; PETER M. MOSHIER; TIMOTHY A. SUBASHI; MICHELLE THERRIEN; PAUL C. WATTS

doi:10.7164/antibiotics.50.1

CP-225, 917 and CP-263, 114, Novel Ras Farnesylation Inhibitors from an Unidentified Fungus

I. Taxonomy, Fermentation, Isolation, and Biochemical Properties

THOMAS T. DABRAH, H. JAMES HARWOOD, LIANG H. HUANG, NANCY D. JANKOVICH, TAKUSHI KANEKO, JIAN-CHENG LI, SARALYN LINDSEY, PETER M. MOSHIER, TIMOTHY A. SUBASHI, MICHELLE THERRIEN, PAUL C. WATTS

Author information

THOMAS T. DABRAH
Natural Product Discovery, Pfizer Central Research
H. JAMES HARWOOD
Natural Product Discovery, Pfizer Central Research
LIANG H. HUANG
Natural Product Discovery, Pfizer Central Research
NANCY D. JANKOVICH
Natural Product Discovery, Pfizer Central Research
TAKUSHI KANEKO
Natural Product Discovery, Pfizer Central Research
JIAN-CHENG LI
Natural Product Discovery, Pfizer Central Research
SARALYN LINDSEY
Natural Product Discovery, Pfizer Central Research
PETER M. MOSHIER
Natural Product Discovery, Pfizer Central Research
TIMOTHY A. SUBASHI
Natural Product Discovery, Pfizer Central Research
MICHELLE THERRIEN
Natural Product Discovery, Pfizer Central Research
PAUL C. WATTS
Natural Product Discovery, Pfizer Central Research

JOURNAL FREE ACCESS

1997 Volume 50 Issue 1 Pages 1-7

DOI https://doi.org/10.7164/antibiotics.50.1

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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 6μM and 20 μM, respectively. CP-225, 917 inhibits squalene synthase with an IC₅₀ value of 43 μM and CP-263, 114 with an IC₅₀ of 160μM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.

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