Frontiers in Anti-Cancer Drug Discovery

Volume: 1

Developments of New Compounds and New Strategies in the Field of Cytotoxic Nucleoside Analogues

Author(s): Lars P. Jordheim, Charles Dumontet

Pp: 525-540 (16)

DOI: 10.2174/978160805161811001010525

* (Excluding Mailing and Handling)

Abstract

Cytotoxic nucleoside analogues are clinically important anticancer drugs. The newer member of this family, gemcitabine, has shown great activity in solid tumours and thus enlarged the spectra of malignancies treated by this family of molecules. However, the clinical use of nucleoside analogues is limited by important side-effects and primary or acquired drug resistance, and there is an unmet medical need for the development of new molecules and technologies allowing a suitable treatment of cancer patients with these agents. In this article we will review literature data and patents concerning (i) the recent development of some novel nucleoside analogues, (ii) oral formulations for cytotoxic nucleoside analogues, (iii) strategies to circumvent acquired resistance to nucleoside analogues, and (iv) gene therapy strategies used to increase cytotoxicity of nucleoside analogues.


Keywords: Nucleoside analogues, Pronucleotides, Gene therapy, CP-4055, CP-4126, MB07133, CYC-682, Ethynylcytidine, OSI-7836, NEO-6002, CPF31, 5mAZC

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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
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
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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 <= 51368230 and j.to_ip >=51368230 )) and ((j.from_date <= 1739834819 and j.to_date >= 1739834819 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1784) 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 <= 51368230 and j.to_ip >=51368230 )) and ((j.from_date <= 1739834819 and j.to_date >= 1739834819 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1784) 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 <= 51368230 and j.to_ip >=51368230 )) and ((j.from_date <= 1739834819 and j.to_date >= 1739834819 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1784)
      500μsalphaeurekaselec_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` = 919 and `b`.`banner_from_date` <= 1739834819 and `b`.`banner_to_date` >= 1739834819 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 919
      • 3: 1739834819
      • 4: 1739834819
      • 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='4b3f29517d1ccd6a043553ceeb52fa18'
      180μsalphaeurekaselec_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\Keywords
    12Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        JQaY0wj7fU4VHikMXfOOuSE6EkUtUYWHWyOAUngn
        uc_cart_id
        4b3f29517d1ccd6a043553ceeb52fa18
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1784" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/1784
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IjFuZUs5U0VOZDVqVGZkN1BBdjF6OFE9PSIsInZhbHVlIjoiR0dodVZCR2JySDhDa2NwUWNBRGtBa2lJaWQ5dUVHMFJPdlRvVmtra1ZBL29IRUdGTHpZUDlYenloK2tXT0dPei9qV3lBNm0yZEdmajVrdmMvT3djRlE9PSIsIm1hYyI6ImFmMmEyYzM3OGYxNjIyNTYzNGExZDZhNDE3Njk3N2I0Y2IyYTJlYWRmZDgwMzRjYWNjOWU1YzgyODlmZTkwOWQiLCJ0YWciOiIifQ%3D%3D; XSRF-TOKEN=eyJpdiI6IlJjUnIveEUrL2pEeGlJM05VNnNxUHc9PSIsInZhbHVlIjoicklHRjM5Mk4xMldjckp3N3FCQ0VtbDc1YTNUODNyUWdDZXJCNmtIUEJhc2ZEdXpZQnhSRUxBSlN0ZEtBU2M1KzAzbkRRemk4eXBkRlFrM3QxZjRvT0NNa0ExQVJaL1UyTWRlUk9KK212bHZ3dC8vaVRzMUJEQWJBUFZncWVFZmQiLCJtYWMiOiIxOGE4NDQ5MGQzM2ExYTgyMjgyM2YxZjM0YTJjYmZiZjE4ZjhiNTgwOTgzM2EwY2QxMWVlYzU4MTYwYzU3MDQ5IiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6Iml2R2lQOEFlNzVneWR6WWdMOE9UUEE9PSIsInZhbHVlIjoib2ZXY3hQTjJldGVvNUhzNG9SNEZFTkM1dG1rSmdTT1lYT0Yrc2RhY1pvQlZzUmh1aTE5akljT1puWDczRWxzV0tTT3BxMU5ud0tJM3JlNlNKY1I3V3hBL0JEY29PUzhSZWpTM1BsakxDRmVMcHJRSDBZNDQzaXZvYWJOWFMxM0MiLCJtYWMiOiIyZjlmMzIzMmE4ZjcwNmE5Nzc3ZWUxNTk5N2VjNWUzMTA1MDZhMWZmMDg1NTQ4MjhjYWNhYTVjMDQ0ZjZmNDI5IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IjFuZUs5U0VOZDVqVGZkN1BBdjF6OFE9PSIsInZhbHVlIjoiR0dodVZCR2JySDhDa2NwUWNBRGtBa2lJaWQ5dUVHMFJPdlRvVmtra1ZBL29IRUdGTHpZUDlYenloK2tXT0dPei9q" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        session_attributes
        0 of 0
        array:5 [ "_token" => "JQaY0wj7fU4VHikMXfOOuSE6EkUtUYWHWyOAUngn" "uc_cart_id" => "4b3f29517d1ccd6a043553ceeb52fa18" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1784" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:26:59GET/chapter/17841121914