title: Zaragozic acids D and D2: potent inhibitors of squalene synthase and of Ras farnesyl-protein transferase.
abstract: Two new zaragozic acids, D and D2, have been isolated from the keratinophilic fungus Amauroascus niger. Zaragozic acids D [4] and D2 [5] are related to the previously described zaragozic acids A [1], B [2], and C [3] and are potent inhibitors of squalene synthase. Furthermore, all the zaragozic acids (A, B, C, D, and D2) are also active against farnesyl transferase. Zaragozic acids D and D2 inhibit farnesyl transferase with IC50 values of 100 nM, while zaragozic acids A and B are less potent.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey.
authors.forename: C
authors.initials: C
authors.lastname: Dufresne
authors.forename: K E
authors.initials: KE
authors.lastname: Wilson
authors.forename: S B
authors.initials: SB
authors.lastname: Singh
authors.forename: D L
authors.initials: DL
authors.lastname: Zink
authors.forename: J D
authors.initials: JD
authors.lastname: Bergstrom
authors.forename: D
authors.initials: D
authors.lastname: Rew
authors.forename: J D
authors.initials: JD
authors.lastname: Polishook
authors.forename: M
authors.initials: M
authors.lastname: Meinz
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: K C
authors.initials: KC
authors.lastname: Silverman
mesh_terms: D019883:Alkyl and Aryl Transferases; D001203:Ascomycota / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D014166:Transferases / Q000037:antagonists & inhibitors*; D014233:Tricarboxylic Acids / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids; C085395:zaragozic acid D; C085396:zaragozic acid D(2); D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D013186:Farnesyl-Diphosphate Farnesyltransferase