Frontiers in Anti-Cancer Drug Discovery

Volume: 1

Targeting Ribonucleotide Reductase for Cancer Chemotherapy

Author(s): Nuno M.F.S.A. Cerqueira, Pedro A. Fernandes, Maria J. Ramos

Pp: 1-30 (30)

DOI: 10.2174/978160805161811001010001

Abstract

Ribonucleotide Reductase (RNR) plays a critical role in DNA synthesis, and is a well-recognized target for cancer chemotherapeutic and antiviral agents. RNR inhibition precludes DNA transcription and repair, from which results cell apoptosis. Many regulation checkpoints concerning RNR activity have been unravelled through the last two decades, with potential use to inhibit enzyme activity. This was accomplished by researchers from different but complementary areas from which several and different inhibitors have resulted. The volume of these studies has generated over 4000 articles since the discovery of RNR in 1960. Some of these compounds have already been approved by FDA and EMEA for the treatment of specific types of cancer, as it is the case of gemcitabine, fluoromethylene and hydroxyurea.

This review summarizes patents and papers during the period 1958 - 2009 dealing with the present understanding of ribonucleotide reductase biochemistry, mechanism of action and the most relevant data concerning RNR inhibition. Special attention is given to the inhibitors that have been patented and are currently in clinical use.


Keywords: Ribonucleotide reductase, inhibitors, antisense, dimerization, radicalscavengers, iron chelators, substrate analogues, allosteric, theoretical results, mechanisms, DNA, gemcitabine, hydroxyurea, GTI-2040, tezacitabine

Related Journals
Related Books
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version163msRequest Duration26MBMemory UsageGET chapter/{id}/{param?}Route
  • warninglog[23:25:09] LOG.warning: Optional parameter $id declared before required parameter $request is implic...
  • Booting (90.52ms)time
  • Application (72.5ms)time
  • 1 x Booting (55.52%)
    90.52ms
    1 x Application (44.47%)
    72.50ms
    12 templates were rendered
    • ebook.chapter_detailschapter_details.blade.php#?blade
    • layouts.chapter_header_sectionchapter_header_section.blade.php#?blade
    • ebook.chapter_top_bannerchapter_top_banner.blade.php#?blade
    • ebook.chapter_bottom_bannerchapter_bottom_banner.blade.php#?blade
    • ebook.ebook_right_bannerebook_right_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET chapter/{id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ChapterController@GetChapterDetails
    namespace
    App\Http\Controllers
    where
    as
    chapter
    file
    app/Http/Controllers/ChapterController.php:1350-1704
    16 statements were executed20.19ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('58953283','',1,1739834709,1739834709) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739834709
      930μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('58953283','/chapter/1759',1,1739834709,1739834709)
      130μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) limit 1
      13.42msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 58953283
      • 1: 58953283
      • 2: 58953283
      • 3: 58953283
      • 4: 58953283
      • 5: 58953283
      • 6: 58953283
      • 7: 58953283
      • 8: 58953283
      • 9: 58953283
      • 10: 58953283
      • 11: 58953283
      • 12: 58953283
      • 13: 58953283
      • 14: 58953283
      • 15: 58953283
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • select * from `chapter` where `chapter_id` = '1759' limit 1
      240μsalphaeurekaselec_live_10_06_2022ChapterController.php#1406
      Bindings
      • 0: 1759
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1406
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`chapter_id` = '1759' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      530μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 1759
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ChapterController.php:1411
      • 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 * from `keywords` where `chapter_id` = '1759'
      250μsalphaeurekaselec_live_10_06_2022ChapterController.php#1415
      Bindings
      • 0: 1759
      Backtrace
      • 15. app/Http/Controllers/ChapterController.php:1415
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select * from `ebook` where `ebook_id` = 132 limit 1
      200μsalphaeurekaselec_live_10_06_2022ChapterController.php#1430
      Bindings
      • 0: 132
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1430
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select count(*) as aggregate from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132) and se.ebook_id!=132 and v.ebook_status='1'
      850μsalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 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
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132) and se.ebook_id!=132 and v.ebook_status='1' limit 10 offset 0
      680μsalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 14. app/Models/Subject.php:238
      • 15. app/Http/Controllers/ChapterController.php:1434
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as aggregate from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132)
      390μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 16. app/Models/Subject.php:255
      • 17. app/Http/Controllers/ChapterController.php:1435
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct j.nid as journal_nid,j.title,j.subtitle,j.issn,j.eissn,j.keyword,sj.journal_id,j.image_file_name,j.flyer_link from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132) limit 10 offset 0
      420μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 14. app/Models/Subject.php:255
      • 15. app/Http/Controllers/ChapterController.php:1435
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `e`.*, `a`.*, `y`.`year`, `e`.`ebook_volume_id` as `ebook_volume_id`, `a`.`ebook_volume_id` as `ebk_vol_id`, `e`.`ebook_id` as `ebk_ebook_id` from `ebook_volume` as `e` left join `author` as `a` on `e`.`ebook_volume_id` = `a`.`ebook_volume_id` left join `year` as `y` on `y`.`id` = `e`.`year_id` where `e`.`ebook_volume_id` = 919 and `e`.`is_uploaded` = 1
      430μsalphaeurekaselec_live_10_06_2022EbookVolume.php#271
      Bindings
      • 0: 919
      • 1: 1
      Backtrace
      • 13. app/Models/EbookVolume.php:271
      • 14. app/Http/Controllers/ChapterController.php:1438
      • 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 count(*) rcd from `ebook_volume` where `ebook_id` = 132 and ebook_volume_id <> 919 limit 1
      230μsalphaeurekaselec_live_10_06_2022EbookVolume.php#999
      Bindings
      • 0: 132
      Backtrace
      • 14. app/Models/EbookVolume.php:999
      • 15. app/Http/Controllers/ChapterController.php:1462
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '1759' and content_type = 'c' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      260μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 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
      • 15. 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` <= 1739834709 and `b`.`banner_to_date` >= 1739834709 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: 1739834709
      • 4: 1739834709
      • 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='bf4f8487f3df37d0cdb9c184e15159c6'
      190μsalphaeurekaselec_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
    15Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        bYxwOffiw8XYqUMmCm2NmFur2CFFuFWYvrMaRiTn
        uc_cart_id
        bf4f8487f3df37d0cdb9c184e15159c6
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1759" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/1759
        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=eyJpdiI6Ik4zUVdwbFJYQmFaSmNMb1dyR1dIWkE9PSIsInZhbHVlIjoiRlBKUVFqWGVJY3QyQXc1ZW5aanNPNE9IOWJZOWprMkU3bnpxdENjOUdOUCttakt2RngwTU9VaUEvWWxKbllJNSIsIm1hYyI6IjdjOTc0MTI5MzMyNDU3MmQxYjU0YzUwM2Y0Zjc0ZDhhZDg2OTc5ZWU5YzFmNjhjNWRjMjVmZDNjMzgwOGIyMzMiLCJ0YWciOiIifQ%3D%3D; XSRF-TOKEN=eyJpdiI6IkxpODk4VThNbEszZHpPL2QweUR1Qnc9PSIsInZhbHVlIjoicXVzUktqSUxOMGg0VGZFYlRGcTd2TTV3QjZ5WnZlZ29zVFpaWTI2UnhXd3ZONWZqdmc4U1RXSXdweERzRE9LZlVJQ2tnclVmSXBzMTZadTl4VEhMVVAvM084Q2VPNzlPemVmRXNhOER4UmpTdVhwVzJNQWpDTWRIb0pOVTU2NEciLCJtYWMiOiJmZDIyY2NhNjliYmY5MjgyOGJhNmQ0YWUyNjZkZGY4YmEyNTFkMDM1ZjFkNjM2MDk0MGIxYTNjMmEyMDk2N2M3IiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6IjVWSU03RVZwUm5RU1htTEhuV1kyQUE9PSIsInZhbHVlIjoiOGpCMFRQQm5MajViSkgrVFNnUi9XVVh6VEhqYXErTno0a0JGbUgxSkNxUGk3MXhYci91ZmhuSGlKZmVHMXBBSjlwMjZiRkJUR3hjMDBUT2ZlSzJMZ1VXVmc5WDllVkhGQjVyTWMxUVZhMFZtUHhCa3NFR1JSTHhMUzF4aGttdTgiLCJtYWMiOiIyOTk1Mjc5ZDZlNmIxYjk2ZDdhMmIyYzUzY2Y0NGQzYWQxNWMzMDgzNzA4NGJkZmY2YjY1MWEyMDlkODI0ZDBmIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ik4zUVdwbFJYQmFaSmNMb1dyR1dIWkE9PSIsInZhbHVlIjoiRlBKUVFqWGVJY3QyQXc1ZW5aanNPNE9IOWJZOWprMkU3bnpxdENjOUdOUCttakt2RngwTU9VaUEvWWxKbllJNSIs" ] "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
        array:3 [ "wayfindertarget" => null "XSRF-TOKEN" => "bYxwOffiw8XYqUMmCm2NmFur2CFFuFWYvrMaRiTn" "alphaeurekaselectnet_session" => "lS1dcdzcFH3EK4YsQrwVrAYqcBcb3bu6TPvft2CV" ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 17 Feb 2025 23:25:09 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IndTOVIrTVpPdWsvcURjL24vWVVVckE9PSIsInZhbHVlIjoiZW9OYnArYUw3YlRZYWh1RGtvb2hyelpMdWdMR0JLUm96MVdYa2gweU56MldOaG1qa2l5cGRJSURQUEdDSU43bGxHWUxva216d09rbkNwcnRwMDFiUjJsa0hHSUlkY25yQlVMbFpZY0RCTCsrbEc0b21uK1kyNjZtSTQ4cUs5eDEiLCJtYWMiOiI2Y2U4OTRjMGY1MjhlOTRjYjQ2ZjM4NTFjOGQwZTJlYWUzZjdmM2E0ODNhYmUwZmY4MjBlOWFlODFiYWViZDg3IiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:25:09 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IndTOVIrTVpPdWsvcURjL24vWVVVckE9PSIsInZhbHVlIjoiZW9OYnArYUw3YlRZYWh1RGtvb2hyelpMdWdMR0JLUm96MVdYa2gweU56MldOaG1qa2l5cGRJSURQUEdDSU43bGxHWUxva" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImdEZ2NuRkRYRTJPN1FRdS9RVVBUS3c9PSIsInZhbHVlIjoiUU00YmY2bTNUekprcjNYR1pJQ0p1R2ZmaS9sUWF4a212YUg4RThxMEZ1emtodksxOHkxQ1d4UFBtWjN6WnF4RWRUYXNBZDcweks0ZGswZXQrYTNRdmswVlk5eU1TV3JwYm15R2xoVTFCSlA2UUpJMG1aTDE4RDc1TmxtZ0xRZmciLCJtYWMiOiI4M2JhOGMzZjFjZWNlZDY0MWFjN2VkY2UwZjQ4MGY2MDdjYThkYzAyZjVjMDMwZDdjNDFhNjE4ZTUzZDFhZDMzIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImdEZ2NuRkRYRTJPN1FRdS9RVVBUS3c9PSIsInZhbHVlIjoiUU00YmY2bTNUekprcjNYR1pJQ0p1R2ZmaS9sUWF4a212YUg4RThxMEZ1emtodksxOHkxQ1d4UFB" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IndTOVIrTVpPdWsvcURjL24vWVVVckE9PSIsInZhbHVlIjoiZW9OYnArYUw3YlRZYWh1RGtvb2hyelpMdWdMR0JLUm96MVdYa2gweU56MldOaG1qa2l5cGRJSURQUEdDSU43bGxHWUxva216d09rbkNwcnRwMDFiUjJsa0hHSUlkY25yQlVMbFpZY0RCTCsrbEc0b21uK1kyNjZtSTQ4cUs5eDEiLCJtYWMiOiI2Y2U4OTRjMGY1MjhlOTRjYjQ2ZjM4NTFjOGQwZTJlYWUzZjdmM2E0ODNhYmUwZmY4MjBlOWFlODFiYWViZDg3IiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:25:09 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IndTOVIrTVpPdWsvcURjL24vWVVVckE9PSIsInZhbHVlIjoiZW9OYnArYUw3YlRZYWh1RGtvb2hyelpMdWdMR0JLUm96MVdYa2gweU56MldOaG1qa2l5cGRJSURQUEdDSU43bGxHWUxva" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImdEZ2NuRkRYRTJPN1FRdS9RVVBUS3c9PSIsInZhbHVlIjoiUU00YmY2bTNUekprcjNYR1pJQ0p1R2ZmaS9sUWF4a212YUg4RThxMEZ1emtodksxOHkxQ1d4UFBtWjN6WnF4RWRUYXNBZDcweks0ZGswZXQrYTNRdmswVlk5eU1TV3JwYm15R2xoVTFCSlA2UUpJMG1aTDE4RDc1TmxtZ0xRZmciLCJtYWMiOiI4M2JhOGMzZjFjZWNlZDY0MWFjN2VkY2UwZjQ4MGY2MDdjYThkYzAyZjVjMDMwZDdjNDFhNjE4ZTUzZDFhZDMzIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImdEZ2NuRkRYRTJPN1FRdS9RVVBUS3c9PSIsInZhbHVlIjoiUU00YmY2bTNUekprcjNYR1pJQ0p1R2ZmaS9sUWF4a212YUg4RThxMEZ1emtodksxOHkxQ1d4UFB" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "bYxwOffiw8XYqUMmCm2NmFur2CFFuFWYvrMaRiTn" "uc_cart_id" => "bf4f8487f3df37d0cdb9c184e15159c6" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1759" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:25:09GET/chapter/17591121617