title: Antiparasitic activities of novel, orally available fumagillin analogs.
abstract: Fumagillin, an irreversible inhibitor of MetAP2, has been shown to potently inhibit growth of malaria parasites in vitro. Here, we demonstrate activity of fumagillin analogs with an improved pharmacokinetic profile against malaria parasites, trypanosomes, and amoebas. A subset of the compounds showed efficacy in a murine malaria model. The observed SAR forms a basis for further optimization of fumagillin based inhibitors against parasitic targets by inhibition of MetAP2.
authors: Praecis Pharmaceuticals, 830 Winter Street, Waltham, MA 02451, USA. christopher.c.arico-muendel@gsk.com
authors: Christopher
authors: C
authors: Arico-Muendel
authors: Paolo A
authors: PA
authors: Centrella
authors: Brooke D
authors: BD
authors: Contonio
authors: Barry A
authors: BA
authors: Morgan
authors: Gary
authors: G
authors: O'Donovan
authors: Christopher L
authors: CL
authors: Paradise
authors: Steven R
authors: SR
authors: Skinner
authors: Barbara
authors: B
authors: Sluboski
authors: Jennifer L
authors: JL
authors: Svendsen
authors: Kerry F
authors: KF
authors: White
authors: Anjan
authors: A
authors: Debnath
authors: Jiri
authors: J
authors: Gut
authors: Nathan
authors: N
authors: Wilson
authors: James H
authors: JH
authors: McKerrow
authors: Joseph L
authors: JL
authors: DeRisi
authors: Philip J
authors: PJ
authors: Rosenthal
authors: Peter K
authors: PK
authors: Chiang
mesh_terms: D000284:Administration, Oral; D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D021261:Parasitic Sensitivity Tests; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases