title: Oreganic acid, a potent inhibitor of ras farnesyl-protein transferase.
abstract: A sulfated tricarboxylic acid fungal metabolite is an inhibitor of human farnesyl-protein transferase (FPTase). The compound, designated as oreganic acid, has a molecular weight of 494, an empirical formula of C22H38O10S and inhibits FPTase with an IC50 value of 14 nM. Oreganic acid is a selective inhibitor of FPTase because it does not inhibit human geranylgeranyl-protein transferase type I (GGPTase-I). It is not a time-dependent inhibitor, reversibly inhibits FPTase, is competitive with respect to farnesyl diphosphate and non-competitive with respect to the Ras acceptor peptide. The structure of oreganic acid resembles that of farnesyl diphosphate and most likely inhibits FPTase by mimicking farnesyl diphosphate at the active site of the enzyme.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Silverman
authors.forename: H
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: C
authors.initials: C
authors.lastname: Cascales
authors.forename: D
authors.initials: D
authors.lastname: Vilella
authors.forename: G F
authors.initials: GF
authors.lastname: Bills
authors.forename: R G
authors.initials: RG
authors.lastname: Jenkins
authors.forename: S B
authors.initials: SB
authors.lastname: Singh
authors.forename: R B
authors.initials: RB
authors.lastname: Lingham
mesh_terms: D019883:Alkyl and Aryl Transferases; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D014166:Transferases / Q000037:antagonists & inhibitors*; D014233:Tricarboxylic Acids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C105186:Oreganic acid; D014233:Tricarboxylic Acids; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D015689:Oncogene Protein p21(ras)