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class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Sam Peacock</h3></div><div class="js-work-strip profile--work_container" data-work-id="63167853"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167853/Development_and_evaluation_of_selective_reversible_LSD1_inhibitors_derived_from_fragments"><img alt="Research paper thumbnail of Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments" class="work-thumbnail" src="https://attachments.academia-assets.com/75680946/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167853/Development_and_evaluation_of_selective_reversible_LSD1_inhibitors_derived_from_fragments">Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments</a></div><div class="wp-workCard_item"><span>Medicinal Chemistry Communication</span><span>, Sep 28, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific deme...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochemical fragment based screen of 2466 compounds. The potency of the initial fragment hit was increased 32-fold through synthesis, with one series of compounds showing clear structure–activity relationships and inhibitory activities in the range of 7 to 187 μM in a biochemical assay. This series also showed selectivity against the related FAD-dependent enzyme mono-amine oxidase A (MAO-A). Although a wide range of irreversible inhibitors of LSD1 have been reported with activities in the low nanomolar range, this work represents one of the first reported examples of a reversible small molecule inhibitor of LSD1 with clear SAR and selectivity against MAO-A, and could provide a platform for the development of more potent reversible inhibitors. Herein, we also report the use of a recently developed cell-based...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a4ca30d1e2059984cf248071e7daa1a1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680946,"asset_id":63167853,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680946/download_file?st=MTczMjQzMDMzNiw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167853"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167853"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167853; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63167853]").text(description); $(".js-view-count[data-work-id=63167853]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63167853; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63167853']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 63167853, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a4ca30d1e2059984cf248071e7daa1a1" } } $('.js-work-strip[data-work-id=63167853]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167853,"title":"Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments","translated_title":"","metadata":{"abstract":"Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochemical fragment based screen of 2466 compounds. 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Although a wide range of irreversible inhibitors of LSD1 have been reported with activities in the low nanomolar range, this work represents one of the first reported examples of a reversible small molecule inhibitor of LSD1 with clear SAR and selectivity against MAO-A, and could provide a platform for the development of more potent reversible inhibitors. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="63167852"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167852/Identification_by_High_Throughput_Screening_of_Pseudomonas_Acyl_Coenzyme_A_Synthetase_Inhibitors"><img alt="Research paper thumbnail of Identification by High-Throughput Screening of Pseudomonas Acyl–Coenzyme A Synthetase Inhibitors" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167852/Identification_by_High_Throughput_Screening_of_Pseudomonas_Acyl_Coenzyme_A_Synthetase_Inhibitors">Identification by High-Throughput Screening of Pseudomonas Acyl–Coenzyme A Synthetase Inhibitors</a></div><div class="wp-workCard_item"><span>SLAS DISCOVERY: Advancing Life Sciences R&D</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl–coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl–coenzyme A, while the third one was competitive with fatty acid binding. A...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167852"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167852"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167852; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63167852]").text(description); $(".js-view-count[data-work-id=63167852]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63167852; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63167852']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 63167852, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=63167852]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167852,"title":"Identification by High-Throughput Screening of Pseudomonas Acyl–Coenzyme A Synthetase Inhibitors","translated_title":"","metadata":{"abstract":"Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl–coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl–coenzyme A, while the third one was competitive with fatty acid binding. A...","publisher":"SAGE Publications","publication_name":"SLAS DISCOVERY: Advancing Life Sciences R\u0026D"},"translated_abstract":"Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl–coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl–coenzyme A, while the third one was competitive with fatty acid binding. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="63167846"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167846/Fragment_based_screening_maps_inhibitor_interactions_in_the_ATP_binding_site_of_checkpoint_kinase_2"><img alt="Research paper thumbnail of Fragment-based screening maps inhibitor interactions in the ATP-binding site of checkpoint kinase 2" class="work-thumbnail" src="https://attachments.academia-assets.com/75680945/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167846/Fragment_based_screening_maps_inhibitor_interactions_in_the_ATP_binding_site_of_checkpoint_kinase_2">Fragment-based screening maps inhibitor interactions in the ATP-binding site of checkpoint kinase 2</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a0a5621dbccb6a30328d8734169cd8bf" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680945,"asset_id":63167846,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680945/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167846"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167846"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167846; 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Furthermore, the CHK2 crystal structures with a quinoxaline-based fragment and its follow-up compound highlight a hydrophobic area above the hinge region not previously explored in rational CHK2 inhibitor design, but which might be exploited to enhance both potency and selectivity of CHK2 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"profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="63167845"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167845/Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization"><img alt="Research paper thumbnail of Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization" class="work-thumbnail" src="https://attachments.academia-assets.com/75680939/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167845/Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization">Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization</a></div><div class="wp-workCard_item"><span>Journal of Medicinal Chemistry</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="acd490fcf900f078c080656963da05f8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680939,"asset_id":63167845,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680939/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action 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Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Journal of Medicinal Chemistry","grobid_abstract_attachment_id":75680939},"translated_abstract":null,"internal_url":"https://www.academia.edu/63167845/Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization","translated_internal_url":"","created_at":"2021-12-03T23:27:48.372-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":128181599,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":75680939,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75680939/thumbnails/1.jpg","file_name":"Aminopyrazine_Inhibitors.pdf","download_url":"https://www.academia.edu/attachments/75680939/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Aminopyrazine_Inhibitors_Binding_to_an_U.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75680939/Aminopyrazine_Inhibitors-libre.pdf?1638605169=\u0026response-content-disposition=attachment%3B+filename%3DAminopyrazine_Inhibitors_Binding_to_an_U.pdf\u0026Expires=1732433937\u0026Signature=WLMhPwK8vpIuZBKeHdimaqVkgTiOJEZ0KzHgevB9rpOOICY5cysn~FPNhzxdY7UgpEtbvW9XmmRejmF1-7XHbNFMA0MQheuu3GlYAT9lUmqpDKs3o~XQfxxS~94-9rVHPSFz8lpBE30I8~iSdQ6J40mKQqyXmDo6gatsuQF-lSDjv8IUUR8faUUqneEktlRaxUz273fwIhjGWInNzd63rL~aW1r70Rb6z96ca2VOrfAYBe4G0xuS-DafOIwGZqIVIatuOBWUAPF553S~MDXyfxsIvrpjWsPFJ5wyXbg3Sus47odBYEzhcAVt2GktpvDSX2bJwbEbrOWWljUIh5HAHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization","translated_slug":"","page_count":17,"language":"en","content_type":"Work","owner":{"id":128181599,"first_name":"Sam","middle_initials":null,"last_name":"Peacock","page_name":"SamPeacock2","domain_name":"independent","created_at":"2019-09-25T23:26:39.764-07:00","display_name":"Sam Peacock","url":"https://independent.academia.edu/SamPeacock2"},"attachments":[{"id":75680939,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75680939/thumbnails/1.jpg","file_name":"Aminopyrazine_Inhibitors.pdf","download_url":"https://www.academia.edu/attachments/75680939/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Aminopyrazine_Inhibitors_Binding_to_an_U.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75680939/Aminopyrazine_Inhibitors-libre.pdf?1638605169=\u0026response-content-disposition=attachment%3B+filename%3DAminopyrazine_Inhibitors_Binding_to_an_U.pdf\u0026Expires=1732433937\u0026Signature=WLMhPwK8vpIuZBKeHdimaqVkgTiOJEZ0KzHgevB9rpOOICY5cysn~FPNhzxdY7UgpEtbvW9XmmRejmF1-7XHbNFMA0MQheuu3GlYAT9lUmqpDKs3o~XQfxxS~94-9rVHPSFz8lpBE30I8~iSdQ6J40mKQqyXmDo6gatsuQF-lSDjv8IUUR8faUUqneEktlRaxUz273fwIhjGWInNzd63rL~aW1r70Rb6z96ca2VOrfAYBe4G0xuS-DafOIwGZqIVIatuOBWUAPF553S~MDXyfxsIvrpjWsPFJ5wyXbg3Sus47odBYEzhcAVt2GktpvDSX2bJwbEbrOWWljUIh5HAHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":531,"name":"Organic Chemistry","url":"https://www.academia.edu/Documents/in/Organic_Chemistry"},{"id":2375,"name":"Medicinal Chemistry","url":"https://www.academia.edu/Documents/in/Medicinal_Chemistry"},{"id":33441,"name":"Macromolecular X-Ray Crystallography","url":"https://www.academia.edu/Documents/in/Macromolecular_X-Ray_Crystallography"},{"id":64568,"name":"Humans","url":"https://www.academia.edu/Documents/in/Humans"},{"id":172083,"name":"Phosphorylation","url":"https://www.academia.edu/Documents/in/Phosphorylation"},{"id":446162,"name":"Medicinal","url":"https://www.academia.edu/Documents/in/Medicinal"},{"id":653665,"name":"Protein Conformation","url":"https://www.academia.edu/Documents/in/Protein_Conformation"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":3889175,"name":"stereoisomerism","url":"https://www.academia.edu/Documents/in/stereoisomerism"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="63167844"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167844/Structure_Guided_Evolution_of_Potent_and_Selective_CHK1_Inhibitors_through_Scaffold_Morphing"><img alt="Research paper thumbnail of Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing" class="work-thumbnail" src="https://attachments.academia-assets.com/75680900/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167844/Structure_Guided_Evolution_of_Potent_and_Selective_CHK1_Inhibitors_through_Scaffold_Morphing">Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing</a></div><div class="wp-workCard_item"><span>Journal of medicinal …</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e3632ca3d2e0a844476decbb7e3c0b05" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680900,"asset_id":63167844,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680900/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167844"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167844"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167844; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63167844]").text(description); $(".js-view-count[data-work-id=63167844]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63167844; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63167844']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 63167844, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "e3632ca3d2e0a844476decbb7e3c0b05" } } $('.js-work-strip[data-work-id=63167844]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167844,"title":"Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing","translated_title":"","metadata":{"abstract":"Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.","publisher":"ACS Publications","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Journal of medicinal …"},"translated_abstract":"Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude 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sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":3889175,"name":"stereoisomerism","url":"https://www.academia.edu/Documents/in/stereoisomerism"}],"urls":[{"id":14765652,"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241339/"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="63167838"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167838/Identification_of_Inhibitors_of_Checkpoint_Kinase_1_through_Template_Screening"><img alt="Research paper thumbnail of Identification of Inhibitors of Checkpoint Kinase 1 through Template Screening" class="work-thumbnail" src="https://attachments.academia-assets.com/75680932/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167838/Identification_of_Inhibitors_of_Checkpoint_Kinase_1_through_Template_Screening">Identification of Inhibitors of Checkpoint Kinase 1 through Template Screening</a></div><div class="wp-workCard_item"><span>Journal of Medicinal Chemistry</span><span>, 2009</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1b072165b726b95d00af7d819f04d044" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680932,"asset_id":63167838,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680932/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa 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Inhibition of CHK1 abrogates DNA damage-induced cell cycle checkpoints and sensitizes p53 deficient cancer cells to genotoxic therapies. Using template screening, a fragment-based approach to small molecule hit generation, we have identified multiple CHK1 inhibitor scaffolds suitable for further optimization. The sequential combination of in silico low molecular weight template selection, a high concentration biochemical assay and hit validation through protein-ligand X-ray crystallography provided 13 template hits from an initial in silico screening library of ca. 15000 compounds. The use of appropriate counter-screening to rule out nonspecific aggregation by test compounds was essential for optimum performance of the high concentration bioassay. One low molecular weight, weakly active purine template hit was progressed by iterative structure-based design to give submicromolar pyrazolopyridines with good ligand efficiency and appropriate CHK1-mediated cellular activity in HT29 colon cancer cells.","publication_date":{"day":null,"month":null,"year":2009,"errors":{}},"publication_name":"Journal of Medicinal Chemistry","grobid_abstract_attachment_id":75680932},"translated_abstract":null,"internal_url":"https://www.academia.edu/63167838/Identification_of_Inhibitors_of_Checkpoint_Kinase_1_through_Template_Screening","translated_internal_url":"","created_at":"2021-12-03T23:27:33.441-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":128181599,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":75680932,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75680932/thumbnails/1.jpg","file_name":"jm900314j.pdf","download_url":"https://www.academia.edu/attachments/75680932/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Identification_of_Inhibitors_of_Checkpoi.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75680932/jm900314j-libre.pdf?1638605169=\u0026response-content-disposition=attachment%3B+filename%3DIdentification_of_Inhibitors_of_Checkpoi.pdf\u0026Expires=1732433937\u0026Signature=QUqpvz2PzsvInlsLDU5ueQrhU-dAdKifpxbjr8Zam6~AjrUVtMB5ZA1iBy0NRgpKw1fw43YEcGN~NZK1Ntc9I6aVviFo~6ZaeT4~0btdgCNDbA7nKPk4Ba1SBDahYwicFsp33l~BOGNwLQ2mJbvw7jLUnRrOOHw064SRi5GYxwPs9X1h5aCvzj2vTRgv98ZrWjtwtzo3ir2q54GSd3KkPXF3SzcrJ6A9zQslvgmREJi-1-5JQemuUftXG5kLAg8cWnj4sAq~fu2~-4EGF6zI6fBgWRcrv5cuirI4b47WniPx1ibEc4btiHHmW-wRyWzjjKH-10xVkY39iyw7oJzTpw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Identification_of_Inhibitors_of_Checkpoint_Kinase_1_through_Template_Screening","translated_slug":"","page_count":10,"language":"en","content_type":"Work","owner":{"id":128181599,"first_name":"Sam","middle_initials":null,"last_name":"Peacock","page_name":"SamPeacock2","domain_name":"independent","created_at":"2019-09-25T23:26:39.764-07:00","display_name":"Sam Peacock","url":"https://independent.academia.edu/SamPeacock2"},"attachments":[{"id":75680932,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75680932/thumbnails/1.jpg","file_name":"jm900314j.pdf","download_url":"https://www.academia.edu/attachments/75680932/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Identification_of_Inhibitors_of_Checkpoi.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75680932/jm900314j-libre.pdf?1638605169=\u0026response-content-disposition=attachment%3B+filename%3DIdentification_of_Inhibitors_of_Checkpoi.pdf\u0026Expires=1732433937\u0026Signature=QUqpvz2PzsvInlsLDU5ueQrhU-dAdKifpxbjr8Zam6~AjrUVtMB5ZA1iBy0NRgpKw1fw43YEcGN~NZK1Ntc9I6aVviFo~6ZaeT4~0btdgCNDbA7nKPk4Ba1SBDahYwicFsp33l~BOGNwLQ2mJbvw7jLUnRrOOHw064SRi5GYxwPs9X1h5aCvzj2vTRgv98ZrWjtwtzo3ir2q54GSd3KkPXF3SzcrJ6A9zQslvgmREJi-1-5JQemuUftXG5kLAg8cWnj4sAq~fu2~-4EGF6zI6fBgWRcrv5cuirI4b47WniPx1ibEc4btiHHmW-wRyWzjjKH-10xVkY39iyw7oJzTpw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":531,"name":"Organic Chemistry","url":"https://www.academia.edu/Documents/in/Organic_Chemistry"},{"id":1177,"name":"Crystallography","url":"https://www.academia.edu/Documents/in/Crystallography"},{"id":2375,"name":"Medicinal Chemistry","url":"https://www.academia.edu/Documents/in/Medicinal_Chemistry"},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction"},{"id":43363,"name":"Screening","url":"https://www.academia.edu/Documents/in/Screening"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":59370,"name":"In Vitro","url":"https://www.academia.edu/Documents/in/In_Vitro"},{"id":64568,"name":"Humans","url":"https://www.academia.edu/Documents/in/Humans"},{"id":69424,"name":"Protein Kinases","url":"https://www.academia.edu/Documents/in/Protein_Kinases"},{"id":296798,"name":"Hydrogen Bonding","url":"https://www.academia.edu/Documents/in/Hydrogen_Bonding"},{"id":446162,"name":"Medicinal","url":"https://www.academia.edu/Documents/in/Medicinal"},{"id":783432,"name":"Biological activity","url":"https://www.academia.edu/Documents/in/Biological_activity"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1152821,"name":"Chemical Synthesis","url":"https://www.academia.edu/Documents/in/Chemical_Synthesis"},{"id":1343089,"name":"Protein Kinase Inhibitors","url":"https://www.academia.edu/Documents/in/Protein_Kinase_Inhibitors"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="13095258" id="papers"><div class="js-work-strip profile--work_container" data-work-id="63167853"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167853/Development_and_evaluation_of_selective_reversible_LSD1_inhibitors_derived_from_fragments"><img alt="Research paper thumbnail of Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments" class="work-thumbnail" src="https://attachments.academia-assets.com/75680946/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167853/Development_and_evaluation_of_selective_reversible_LSD1_inhibitors_derived_from_fragments">Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments</a></div><div class="wp-workCard_item"><span>Medicinal Chemistry Communication</span><span>, Sep 28, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific deme...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochemical fragment based screen of 2466 compounds. The potency of the initial fragment hit was increased 32-fold through synthesis, with one series of compounds showing clear structure–activity relationships and inhibitory activities in the range of 7 to 187 μM in a biochemical assay. This series also showed selectivity against the related FAD-dependent enzyme mono-amine oxidase A (MAO-A). Although a wide range of irreversible inhibitors of LSD1 have been reported with activities in the low nanomolar range, this work represents one of the first reported examples of a reversible small molecule inhibitor of LSD1 with clear SAR and selectivity against MAO-A, and could provide a platform for the development of more potent reversible inhibitors. Herein, we also report the use of a recently developed cell-based...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a4ca30d1e2059984cf248071e7daa1a1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680946,"asset_id":63167853,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680946/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&st=MTczMjQzMDMzNiw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167853"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167853"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167853; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63167853]").text(description); $(".js-view-count[data-work-id=63167853]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63167853; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63167853']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 63167853, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a4ca30d1e2059984cf248071e7daa1a1" } } $('.js-work-strip[data-work-id=63167853]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167853,"title":"Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments","translated_title":"","metadata":{"abstract":"Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochemical fragment based screen of 2466 compounds. 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These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl–coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl–coenzyme A, while the third one was competitive with fatty acid binding. A...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167852"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167852"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167852; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63167852]").text(description); $(".js-view-count[data-work-id=63167852]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63167852; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63167852']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 63167852, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=63167852]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167852,"title":"Identification by High-Throughput Screening of Pseudomonas Acyl–Coenzyme A Synthetase Inhibitors","translated_title":"","metadata":{"abstract":"Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. 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A...","publisher":"SAGE Publications","publication_name":"SLAS DISCOVERY: Advancing Life Sciences R\u0026D"},"translated_abstract":"Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl–coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. 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small molecule inhibitors of PKB/AKT in a high throughput screen</a></div><div class="wp-workCard_item"><span>European Journal of Cancer Supplements</span><span>, 2004</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167851"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167851"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167851; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var 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Conjugate Vaccine in Hib-Diphtheria-Tetanus Toxoids-Acellular Pertussis Combination Vaccines: A Study in a Rat Model" class="work-thumbnail" src="https://attachments.academia-assets.com/75680940/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167849/Suppression_and_Modulation_of_Cellular_and_Humoral_Immune_Responses_to_Haemophilus_influenzae_Type_B_Hib_Conjugate_Vaccine_in_Hib_Diphtheria_Tetanus_Toxoids_Acellular_Pertussis_Combination_Vaccines_A_Study_in_a_Rat_Model">Suppression and Modulation of Cellular and Humoral Immune Responses to Haemophilus influenzae Type B (Hib) Conjugate Vaccine in Hib-Diphtheria-Tetanus Toxoids-Acellular Pertussis Combination Vaccines: A Study in a Rat Model</a></div><div class="wp-workCard_item"><span>The Journal of Infectious Diseases</span><span>, 2005</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="30e3d49f805d425125a4e20703775ff7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680940,"asset_id":63167849,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680940/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&st=MTczMjQzMDMzNiw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167849"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span 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class="work-thumbnail" src="https://attachments.academia-assets.com/75680941/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167848/Identification_of_inhibitors_of_the_kinase_activity_of_oncogenic_V600E_BRAF_in_an_enzyme_cascade_high_throughput_screen">Identification of inhibitors of the kinase activity of oncogenic V600E BRAF in an enzyme cascade high-throughput screen</a></div><div class="wp-workCard_item"><span>Journal of Biomolecular Screening</span><span>, Mar 1, 2006</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="18ed0150443f2d4eaf50b96896d4648d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "18ed0150443f2d4eaf50b96896d4648d" } } $('.js-work-strip[data-work-id=63167848]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167848,"title":"Identification of inhibitors of the kinase activity of oncogenic V600E BRAF in an enzyme cascade high-throughput screen","translated_title":"","metadata":{"grobid_abstract":"The Cancer Genome Project has identified several oncogenic mutations in BRAF that represent important opportunities for cancer drug discovery. The V600E BRAF mutation accounts for approximately 90% of the mutations identified. A strong case has emerged from molecular, cellular, and structural studies for the identification and development of inhibitors of this mutated BRAF protein. The authors have developed and run a high-throughput screen to find inhibitors of V600E BRAF using an enzyme cascade assay in which oncogenic BRAF activates MEK1, which in turn activates ERK2, which then phosphorylates the transcription factor ELK1. A phosphospecific antibody, Europium-labeled secondary antibody, and a time-resolved fluorescent readout were used to measure phosphorylation of ELK1. Overall assay variation was 12.4%. The assay was used to screen 64,000 compounds with an overall Z′ factor of 0.58 ± 0.12. A series of 3,5,di-substituted pyridines were identified as inhibitors of the cascade assay. 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href="https://www.academia.edu/63167845/Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization">Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization</a></div><div class="wp-workCard_item"><span>Journal of Medicinal Chemistry</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="acd490fcf900f078c080656963da05f8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680939,"asset_id":63167845,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680939/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span 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Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Journal of Medicinal Chemistry","grobid_abstract_attachment_id":75680939},"translated_abstract":null,"internal_url":"https://www.academia.edu/63167845/Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization","translated_internal_url":"","created_at":"2021-12-03T23:27:48.372-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":128181599,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":75680939,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75680939/thumbnails/1.jpg","file_name":"Aminopyrazine_Inhibitors.pdf","download_url":"https://www.academia.edu/attachments/75680939/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Aminopyrazine_Inhibitors_Binding_to_an_U.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75680939/Aminopyrazine_Inhibitors-libre.pdf?1638605169=\u0026response-content-disposition=attachment%3B+filename%3DAminopyrazine_Inhibitors_Binding_to_an_U.pdf\u0026Expires=1732433937\u0026Signature=WLMhPwK8vpIuZBKeHdimaqVkgTiOJEZ0KzHgevB9rpOOICY5cysn~FPNhzxdY7UgpEtbvW9XmmRejmF1-7XHbNFMA0MQheuu3GlYAT9lUmqpDKs3o~XQfxxS~94-9rVHPSFz8lpBE30I8~iSdQ6J40mKQqyXmDo6gatsuQF-lSDjv8IUUR8faUUqneEktlRaxUz273fwIhjGWInNzd63rL~aW1r70Rb6z96ca2VOrfAYBe4G0xuS-DafOIwGZqIVIatuOBWUAPF553S~MDXyfxsIvrpjWsPFJ5wyXbg3Sus47odBYEzhcAVt2GktpvDSX2bJwbEbrOWWljUIh5HAHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Aminopyrazine_Inhibitors_Binding_to_an_Unusual_Inactive_Conformation_of_the_Mitotic_Kinase_Nek2_SAR_and_Structural_Characterization","translated_slug":"","page_count":17,"language":"en","content_type":"Work","owner":{"id":128181599,"first_name":"Sam","middle_initials":null,"last_name":"Peacock","page_name":"SamPeacock2","domain_name":"independent","created_at":"2019-09-25T23:26:39.764-07:00","display_name":"Sam Peacock","url":"https://independent.academia.edu/SamPeacock2"},"attachments":[{"id":75680939,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75680939/thumbnails/1.jpg","file_name":"Aminopyrazine_Inhibitors.pdf","download_url":"https://www.academia.edu/attachments/75680939/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Aminopyrazine_Inhibitors_Binding_to_an_U.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75680939/Aminopyrazine_Inhibitors-libre.pdf?1638605169=\u0026response-content-disposition=attachment%3B+filename%3DAminopyrazine_Inhibitors_Binding_to_an_U.pdf\u0026Expires=1732433937\u0026Signature=WLMhPwK8vpIuZBKeHdimaqVkgTiOJEZ0KzHgevB9rpOOICY5cysn~FPNhzxdY7UgpEtbvW9XmmRejmF1-7XHbNFMA0MQheuu3GlYAT9lUmqpDKs3o~XQfxxS~94-9rVHPSFz8lpBE30I8~iSdQ6J40mKQqyXmDo6gatsuQF-lSDjv8IUUR8faUUqneEktlRaxUz273fwIhjGWInNzd63rL~aW1r70Rb6z96ca2VOrfAYBe4G0xuS-DafOIwGZqIVIatuOBWUAPF553S~MDXyfxsIvrpjWsPFJ5wyXbg3Sus47odBYEzhcAVt2GktpvDSX2bJwbEbrOWWljUIh5HAHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":531,"name":"Organic Chemistry","url":"https://www.academia.edu/Documents/in/Organic_Chemistry"},{"id":2375,"name":"Medicinal Chemistry","url":"https://www.academia.edu/Documents/in/Medicinal_Chemistry"},{"id":33441,"name":"Macromolecular X-Ray Crystallography","url":"https://www.academia.edu/Documents/in/Macromolecular_X-Ray_Crystallography"},{"id":64568,"name":"Humans","url":"https://www.academia.edu/Documents/in/Humans"},{"id":172083,"name":"Phosphorylation","url":"https://www.academia.edu/Documents/in/Phosphorylation"},{"id":446162,"name":"Medicinal","url":"https://www.academia.edu/Documents/in/Medicinal"},{"id":653665,"name":"Protein Conformation","url":"https://www.academia.edu/Documents/in/Protein_Conformation"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":3889175,"name":"stereoisomerism","url":"https://www.academia.edu/Documents/in/stereoisomerism"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="63167844"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63167844/Structure_Guided_Evolution_of_Potent_and_Selective_CHK1_Inhibitors_through_Scaffold_Morphing"><img alt="Research paper thumbnail of Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing" class="work-thumbnail" src="https://attachments.academia-assets.com/75680900/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167844/Structure_Guided_Evolution_of_Potent_and_Selective_CHK1_Inhibitors_through_Scaffold_Morphing">Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing</a></div><div class="wp-workCard_item"><span>Journal of medicinal …</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e3632ca3d2e0a844476decbb7e3c0b05" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680900,"asset_id":63167844,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75680900/download_file?st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&st=MTczMjQzMDMzNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63167844"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63167844"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63167844; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63167844]").text(description); $(".js-view-count[data-work-id=63167844]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63167844; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63167844']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 63167844, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "e3632ca3d2e0a844476decbb7e3c0b05" } } $('.js-work-strip[data-work-id=63167844]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63167844,"title":"Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing","translated_title":"","metadata":{"abstract":"Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.","publisher":"ACS Publications","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Journal of medicinal …"},"translated_abstract":"Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude 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/></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63167838/Identification_of_Inhibitors_of_Checkpoint_Kinase_1_through_Template_Screening">Identification of Inhibitors of Checkpoint Kinase 1 through Template Screening</a></div><div class="wp-workCard_item"><span>Journal of Medicinal Chemistry</span><span>, 2009</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1b072165b726b95d00af7d819f04d044" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75680932,"asset_id":63167838,"asset_type":"Work","button_location":"profile"}" 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