title: Towards a modern definition of vitamin E-evidence for a quinone hypothesis.
abstract: We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.
authors.affiliation: Edison Pharmaceuticals, Inc., 350 North Bernardo Avenue, Mountain View, CA 94043, USA. bshrader@edisonpharma.com
authors.forename: William D
authors.initials: WD
authors.lastname: Shrader
authors.forename: Akiko
authors.initials: A
authors.lastname: Amagata
authors.forename: Adam
authors.initials: A
authors.lastname: Barnes
authors.forename: Andrew
authors.initials: A
authors.lastname: Hinman
authors.forename: Orion
authors.initials: O
authors.lastname: Jankowski
authors.forename: Edgar
authors.initials: E
authors.lastname: Lee
authors.forename: Viktoria
authors.initials: V
authors.lastname: Kheifets
authors.forename: Ryo
authors.initials: R
authors.lastname: Komatsuzaki
authors.forename: Paul
authors.initials: P
authors.lastname: Mollard
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Murase
authors.forename: Patrice
authors.initials: P
authors.lastname: Rioux
authors.forename: Kieron
authors.initials: K
authors.lastname: Wesson
authors.forename: Guy
authors.initials: G
authors.lastname: Miller
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005347:Fibroblasts / Q000378:metabolism; D005621:Friedreich Ataxia / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000737:chemistry; D051379:Mice; D015162:Micronucleus Tests; D008956:Models, Chemical; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D052756:Nutritional Sciences; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011809:Quinones / Q000737:chemistry*; D051381:Rats; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D011809:Quinones; D014810:Vitamin E; C002421:tocopherylquinone; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D006867:Hydrolases; D024502:alpha-Tocopherol