Comparative study of the inhibition of rat and tobacco squalene synthase by squalestatins.
Squalestatins 1-3 and a series of S1 analogues modified at the C-1, C-3, C-4 or C-6 position were able to inhibit squalene synthase, a key enzyme in both cholesterol and phytosterol biosynthesis, in microsomal rich preparations from both rat liver and N. tabacum. IC50 values varied between 4 and 2000 nM, and similar inhibition values were observed in both systems. The structural requirements for maximal activity at each position are discussed.
Fulton
D C
DC
Department of Applied Biology, University of Hull, U.K.
Tait
M
M
Threlfall
D R
DR
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D010947:Plants, Toxic; D051381:Rats; D014026:Nicotiana / Q000201:enzymology*; D014233:Tricarboxylic Acids / Q000737:chemistry / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids; C075117:squalestatin 1; C093905:squalestatin 2; C093906:squalestatin 3; D013186:Farnesyl-Diphosphate Farnesyltransferase