Author(s): E. G. Solon, S. K. Balani and F. W. Lee
Page: [451 - 462] Pages: 12
* (Excluding Mailing and Handling)
In the drug discovery process the pharmacokinetic screening, drug stability studies, evaluation of metabolites, CYP involvement, enzyme induction and inhibition, and excretion studies play a major role. The use of more sensitive and novel detection systems have made the discovery process less cumbersome than in previous years. In particular, the use of whole-body autoradiography (WBA) for tissue distribution, which was once considered an impractical tool, owing to the long turn around time (4-10 weeks), is coming to the forefront for rapidly resolving issues encountered in discovery. In todays research environment early lead compounds can be radio-labeled and whole-body sections imaged quickly (3-5 days) using new techniques, which has made 14C- and 3H-WBA a viable tool. The technique has been used in vivo in species from mice to monkeys, and ex vivo and/or in vitro in larger animals and humans. WBA has considerable merit in identifying “pharmacodefficient” compounds and providing insight on mechanistic questions. WBA data can provide information related to tissue pharmacokinetics, routes of elimination, CYP or Pgp mediated drug-drug interactions, tissue distribution, site specific drug localization and retention, metabolism, clearance, compound solubility issues, routes of administration, penetration into specific targets (e.g., tumors), tissue binding (e.g., melanin), and interspecies kinetics. Thus, WBA is quickly becoming part of the battery of studies conducted during the lead optimization process to select optimal drug candidates. Examples of the use of the WBA tool in early discovery are reviewed.
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CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58835642 and j.to_ip >=58835642 )) and ((j.from_date <= 1734980866 and j.to_date >= 1734980866 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 9688)
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select * from `article` where `first_page` < '451' and is_uploaded = 1 and issue_id = 1842 order by cast(first_page as SIGNED) desc limit 1
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select * from `article` where `last_page` > '462' and is_uploaded = 1 and issue_id = 1842 order by cast(first_page as SIGNED) asc limit 1
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select `language_id` from `multilanguage` where `short_code` = 'en'
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select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
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select `id` from `multilanguage_article` where `article_id` = 9688 limit 1
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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` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 15 and `b`.`banner_from_date` <= 1734980866 and `b`.`banner_to_date` >= 1734980866 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
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select count(*) as aggregate from `uc_cart_products` where cart_id='99cf5198dcb9f74dc7c8c44bbc479bff'
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|
200
[]
[]
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