title: 4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.
abstract: Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. lara.s.kallander@gsk.com
authors.forename: Lara S
authors.initials: LS
authors.lastname: Kallander
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Wenfang
authors.initials: W
authors.lastname: Chen
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Tomaszek
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: Tew
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Meek
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Hofmann
authors.forename: Christina K
authors.initials: CK
authors.lastname: Schulz-Pritchard
authors.forename: Ward W
authors.initials: WW
authors.lastname: Smith
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Janson
authors.forename: M Dominic
authors.initials: MD
authors.lastname: Ryan
authors.forename: Gui-Feng
authors.initials: GF
authors.lastname: Zhang
authors.forename: Kyung O
authors.initials: KO
authors.lastname: Johanson
authors.forename: Robert B
authors.initials: RB
authors.lastname: Kirkpatrick
authors.forename: Thau F
authors.initials: TF
authors.lastname: Ho
authors.forename: Paul W
authors.initials: PW
authors.lastname: Fisher
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mattern
authors.forename: Randall K
authors.initials: RK
authors.lastname: Johnson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hansbury
authors.forename: James D
authors.initials: JD
authors.lastname: Winkler
authors.forename: Keith W
authors.initials: KW
authors.lastname: Ward
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Veber
authors.forename: Scott K
authors.initials: SK
authors.lastname: Thompson
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000378:metabolism; D003094:Collagen; D018360:Crystallography, X-Ray; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation; D006801:Humans; D007797:Laminin; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011509:Proteoglycans; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D014230:Triazoles; C059485:matrigel; D003035:Cobalt; D003094:Collagen; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases