Frontiers in Drug Design and Discovery

Volume: 4

Glutathione Transferases in Drug Discovery and Development: Towards Safer and Efficacious Drugs

Author(s): Katholiki Skopelitou, Dimitris Platis, Irene Axarli and Nikolaos E. Labrou

Pp: 23-42 (20)

DOI: 10.2174/978160805202810904010023

* (Excluding Mailing and Handling)

Abstract

Glutathione transferases (GSTs) are enzymes involved in cellular detoxification by catalysing the nucleophilic attack of glutathione (GSH) on the electrophilic centre of a number of electrophilic compounds of both endogenous and exogenous origins. This conjugation reaction usually makes the electrophilic substrates more water soluble and, thereby, facilitates their excretion from the body. Determination of metabolic properties of a new chemical entity (NCE) is one of the most important steps during the drug discovery and development process. Nowadays, in vitro methods are used for early estimation and prediction of in vivo metabolism of NCEs. In this review detailed descriptions are given of several biotransformation reactions catalyzed by GSTs that can be used at very early phases of drug development, thereby enabling unsuitable candidates to be eliminated from consideration much earlier in the drug discovery process. Knowledge of the structure-function relationships in classes of compounds that are substrates for GSTs enables the design of molecules that can be stable, or labile which has potential applications in drug and prodrug design.

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      • 14. app/Models/UserAccess/UserAccess.php:784
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      • 16. app/Models/Subject.php:238
      • 17. app/Http/Controllers/ChapterController.php:1434
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 14. app/Models/Subject.php:238
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      • 16. app/Models/Subject.php:255
      • 17. app/Http/Controllers/ChapterController.php:1435
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      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      290μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59584110 and j.to_ip >=59584110 )) and ((j.from_date <= 1740514563 and j.to_date >= 1740514563 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2199) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59584110 and j.to_ip >=59584110 )) and ((j.from_date <= 1740514563 and j.to_date >= 1740514563 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2199) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59584110 and j.to_ip >=59584110 )) and ((j.from_date <= 1740514563 and j.to_date >= 1740514563 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2199)
      650μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 945 and `b`.`banner_from_date` <= 1740514563 and `b`.`banner_to_date` >= 1740514563 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.26msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 945
      • 3: 1740514563
      • 4: 1740514563
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='fb17b0ebf3aab627931ea9451c387416'
      240μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        XZ6m9ESV5J2gWK8Q0lDb3SA6MgVfLdP2wak32i6P
        uc_cart_id
        fb17b0ebf3aab627931ea9451c387416
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2199" ]
        _flash
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        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:16:03GET/chapter/2199112192