Kampanols: novel Ras farnesyl-protein transferase inhibitors from Stachybotrys kampalensis.
Farnesyl-protein transferase (FPTase) is a critical enzyme that participates in the post-translational modification of the Ras protein. Inhibitors of this enzyme have the potential of being novel anticancer agents for tumors in which the ras oncogene is found mutated and contributes to cell transformation. Continued screening of natural product extracts led to the isolation of kampanols, which are novel and specific inhibitors of FPTase. The most active kampanols exhibited IC50 values between 7 to 13 microM against human recombinant FPTase. The isolation, structure determination, and biological activity of these compounds are described.
Singh
S B
SB
Merck Research Laboratories, Rahway, NJ 07065, USA.
Zink
D L
DL
Williams
M
M
Polishook
J D
JD
Sanchez
M
M
Silverman
K C
KC
Lingham
R B
RB
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011905:Genes, ras; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013729:Terpenes; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase