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ResidenceTimer™ - Oncolines B.V.

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100%;max-width: 1100px;"><li class="menu-item menu-item-type-custom menu-item-object-custom menu-item-has-children menu-item-9824 fusion-megamenu-submenu fusion-megamenu-columns-3 col-lg-4 col-md-4 col-sm-4" ><div class='fusion-megamenu-title'><span class="awb-justify-title">Oncolines<sup>®</sup> Profiling</span></div><ul class="sub-menu"><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9814" ><a title="Oncolines® Profiling Explained" href="https://www.oncolines.com/oncolines/oncolines-explained-facts/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon fa-angle-right fas" aria-hidden="true"></i></span>Oncolines® Profiling Explained</span></a></li><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-has-children menu-item-9815" ><a href="https://www.oncolines.com/oncolines/proliferation-assays/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon 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menu-item-object-page menu-item-has-children menu-item-9820" ><a title="Oncolines® Bioinformatics" href="https://www.oncolines.com/oncolines/bioinformatics/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon fa-angle-right fas" aria-hidden="true"></i></span>Oncolines® Bioinformatics</span> <span class="fusion-caret"><i class="fusion-dropdown-indicator" aria-hidden="true"></i></span></a><ul class="sub-menu deep-level"><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9821" ><a href="https://www.oncolines.com/oncolines/bioinformatics/gene-mutation-analysis/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon fa-angle-right fas" aria-hidden="true"></i></span>Gene Mutation Analysis</span></a></li><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9822" ><a href="https://www.oncolines.com/oncolines/bioinformatics/bioinformatics-tissue-sensitivity/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon fa-angle-right fas" aria-hidden="true"></i></span>Tissue Sensitivity Analysis</span></a></li><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9823" ><a href="https://www.oncolines.com/oncolines/bioinformatics/comparative-analysis-via-oncolines-profiler/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon fa-angle-right fas" aria-hidden="true"></i></span>Comparative Analysis</span></a></li></ul></li><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9819" ><a href="https://www.oncolines.com/oncolines/gene-expression-via-genenominator/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-icon"><i class="glyphicon fa-angle-right fas" aria-hidden="true"></i></span>GeneNominator™</span></a></li><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9818" ><a 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class="fusion-arrow-highlight"><span><span class="fusion-megamenu-bullet"></span>Overview of Assays for SPR</span></a></li></ul></li><li class="menu-item menu-item-type-custom menu-item-object-custom menu-item-has-children menu-item-9859 fusion-megamenu-submenu fusion-megamenu-columns-3 col-lg-4 col-md-4 col-sm-4" ><div class='fusion-megamenu-title'><span class="awb-justify-title">Biochemistry</span></div><ul class="sub-menu"><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9855" ><a href="https://www.oncolines.com/biochemistry/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-bullet"></span>Molecular Interactions</span></a></li><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-9854" ><a href="https://www.oncolines.com/biochemistry/kinome-profiling/" class="fusion-arrow-highlight"><span><span class="fusion-megamenu-bullet"></span>Kinome Profiling</span></a></li><li class="menu-item menu-item-type-post_type 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href="https://www.oncolines.com/blog/author/manon-sv/" title="Posts by Oncolines®" rel="author">Oncolines®</a></span></span><span class="updated rich-snippet-hidden">2024-10-19T23:17:46+02:00</span> <div class="post-content"> <style type="text/css">body #gform_wrapper_2 {border-width: 0; border-style: solid;}body #gform_wrapper_2 .gform_heading {border-style: solid;border-width: 0px;}body #gform_wrapper_2 .gform_footer .gform_button,body #gform_wrapper_2 .gform_page_footer .gform_button,body #gform_wrapper_2 .gform_page_footer .gform_previous_button,body #gform_wrapper_2 .gform_page_footer .gform_next_button,body #gform_wrapper_2 .gfield#field_submit .gform-button{border-style: solid;border-radius:50px;-web-border-radius:50px;-moz-border-radius:50px;border-width: 0px;}body #gform_wrapper_2 .gform_footer .gform_button:hover,body #gform_wrapper_2 .gform_page_footer .gform_button:hover,body #gform_wrapper_2 .gform_page_footer .gform_previous_button:hover,body #gform_wrapper_2 .gform_page_footer .gform_next_button:hover,body #gform_wrapper_2 .gfield#field_submit .gform-button:hover {border-style: solid;border-style: solid;}body #gform_wrapper_2 .gform_footer button.mdc-button:hover {}/* Styling for Tablets */@media only screen and ( max-width: 800px ) and ( min-width:481px ) {}/* Styling for phones */@media only screen and ( max-width: 480px ) {}/*Option to add custom CSS */</style><div class="fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:calc( 1100px + 0px );margin-left: calc(-0px / 2 );margin-right: calc(-0px / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-bg-blend:overlay;--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:0px;--awb-margin-bottom-large:20px;--awb-spacing-left-large:0px;--awb-width-medium:100%;--awb-spacing-right-medium:0px;--awb-spacing-left-medium:0px;--awb-width-small:100%;--awb-spacing-right-small:0px;--awb-spacing-left-small:0px;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-title title fusion-title-1 sep-underline sep-solid fusion-title-text fusion-title-size-one"><h1 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:27;line-height:1.2;"><h1>ResidenceTimer™ Surface Plasmon Resonance (SPR) Using Biacore</h1></h1></div><div class="fusion-title title fusion-title-2 sep-underline sep-solid fusion-title-text fusion-title-size-two"><h2 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:17.25;--minFontSize:17.25;line-height:2;">Determination of Drug-Target Interaction</h2></div></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-2 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:1144px;margin-left: calc(-4% / 2 );margin-right: calc(-4% / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-1 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-bg-blend:overlay;--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-title title fusion-title-3 sep-underline sep-solid fusion-title-text fusion-title-size-one"><h1 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:27;line-height:1.2;">Differentiation of Drug Candidates by Binding Characteristics</h1></div><div class="fusion-text fusion-text-1"><p>Determination of target residence time may help you to differentiate your drug candidate from competitor compounds. Drugs that reside on their target for several hours will have the advantage that their pharmacodynamic effect will last even after the drug has been eliminated from systemic circulation. Our profiling service via ResidenceTimer™ gives a mechanistic rationale for the distinct pharmacological features of a drug candidate compared to another.</p> </div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-2 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-bg-blend:overlay;--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><ul style="--awb-iconcolor:var(--awb-color5);--awb-line-height:27.2px;--awb-icon-width:27.2px;--awb-icon-height:27.2px;--awb-icon-margin:11.2px;--awb-content-margin:38.4px;" class="fusion-checklist fusion-checklist-1 fusion-checklist-default fusion-checklist-divider type-icons"><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Surface plasmon resonance (SPR) via Biacore</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Single-cycle kinetics for accurate determination of on- and off-rate</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Direct measurement of binding to target without a probe</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content">Off-the-shelf assays for more than 180 kinases<div class="fusion-alignright"><a class="fusion-button button-flat fusion-button-default-size button-default fusion-button-default button-1 fusion-button-default-span fusion-button-default-type" target="_self" href="https://www.oncolines.com/residencetimer/tabel-residencetimer-off-the-shelf-assays/"><span class="fusion-button-text">View list</span></a></div></div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Protein-protein interaction, antibody-antigen interaction</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Custom assay development capabilities</p> </div></li></ul></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-3 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-bg-blend:overlay;--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-builder-row fusion-builder-row-inner fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="width:104% !important;max-width:104% !important;margin-left: calc(-4% / 2 );margin-right: calc(-4% / 2 );"><div class="fusion-layout-column fusion_builder_column_inner fusion-builder-nested-column-0 fusion_builder_column_inner_1_1 1_1 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-image-element " style="--awb-max-width:600px;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);"><span class=" fusion-imageframe imageframe-none imageframe-1 hover-type-none"><a href="https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK-.png" class="fusion-lightbox" data-rel="iLightbox[ff3fb490d897afdaa22]" data-title="Interaction Of TTK Inhibitors With TTK" title="Interaction Of TTK Inhibitors With TTK"><img fetchpriority="high" decoding="async" width="827" height="453" alt="Kinase tree folder " src="https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK-.png" data-orig-src="https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK-.png" class="lazyload img-responsive wp-image-4415" srcset="data:image/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27827%27%20height%3D%27453%27%20viewBox%3D%270%200%20827%20453%27%3E%3Crect%20width%3D%27827%27%20height%3D%27453%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E" data-srcset="https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK--200x110.png 200w, https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK--400x219.png 400w, https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK--600x329.png 600w, https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK--800x438.png 800w, https://www.oncolines.com/wp-content/uploads/2020/06/Interaction-of-TTK-inhibitors-with-TTK-.png 827w" data-sizes="auto" data-orig-sizes="(max-width: 1024px) 100vw, (max-width: 640px) 100vw, 827px" /></a></span></div></div></div></div></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-3 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-margin-top:1.5em;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:1144px;margin-left: calc(-4% / 2 );margin-right: calc(-4% / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-4 fusion_builder_column_1_3 1_3 fusion-flex-column fusion-flex-align-self-stretch" style="--awb-padding-top:0.5em;--awb-padding-right:4%;--awb-padding-bottom:0.5em;--awb-padding-left:4%;--awb-bg-color:var(--awb-color3);--awb-bg-color-hover:var(--awb-color3);--awb-bg-size:cover;--awb-width-large:33.333333333333%;--awb-margin-top-large:0px;--awb-spacing-right-large:5.76%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:5.76%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-text fusion-text-2"><h6><strong>Above, right</strong>: Overlay of binding curves for TTK inhibitors. In this chart, NTRC 0066-0 binds to TTK with the longest target residence time. Staurosporine and Mps-Bay-2B have a short residence time on TTK (adapted from Maia <em>et al.</em>, 2015).<br /> <strong>Below,</strong> <strong>right</strong>: Binding parameters for TTK inhibitors on TTK.</h6> </div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-5 fusion_builder_column_2_3 2_3 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:66.666666666667%;--awb-margin-top-large:0px;--awb-spacing-right-large:2.88%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:2.88%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"> <div class="table-1"> <table> <tbody> <tr> <td width="120"><strong>Compound</strong></td> <td width="160"><strong><em>k</em><sub>a </sub>(M<sup>-1 </sup>s<sup>-1</sup>)</strong></td> <td width="120"><strong><em>k</em><sub>d </sub>(s<sup>-1</sup>)</strong></td> <td width="120"><strong><em>K</em><sub>D </sub>(M)</strong></td> <td width="120"><strong><em>t</em><sub>1/2 </sub>(s)</strong></td> </tr> <tr> <td width="113">NTRC 0066-0</td> <td width="88">5.1E+05</td> <td width="101">2.2E-04</td> <td width="101">4.3E-10</td> <td width="101">3185</td> </tr> <tr> <td width="113">AZD 3146</td> <td width="88">3.5E+07</td> <td width="101">1.8E-01</td> <td width="101">5.0E-09</td> <td width="101">4</td> </tr> <tr> <td width="113">MPI-0479605</td> <td width="88">1.6E+06</td> <td width="101">9.7E-04</td> <td width="101">5.9E-10</td> <td width="101">718</td> </tr> <tr> <td width="113">Mps-Bay-2B</td> <td width="88">2.2E+06</td> <td width="101">2.2E-02</td> <td width="101">1.0E-08</td> <td width="101">31</td> </tr> <tr> <td width="113">Staurosporine</td> <td width="88">6.7E+05</td> <td width="101">1.6E-02</td> <td width="101">2.5E-08</td> <td width="101">42</td> </tr> </tbody> </table> </div> </div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-4 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-margin-top:1em;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:1144px;margin-left: calc(-4% / 2 );margin-right: calc(-4% / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-6 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-bg-blend:overlay;--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-title title fusion-title-4 sep-underline sep-solid fusion-title-text fusion-title-size-one"><h1 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:27;line-height:1.2;">Selectivity Within a Family of Targets</h1></div><div class="fusion-text fusion-text-3"><p>Kinetic selectivity for an isoform within a family of kinases can guide the selection of drug candidates for further studies. Using SPR binding analysis, it was shown that the PI3K-γ/δ inhibitor duvelisib binds to PI3K-δ and PI3K-γ with relatively long target residence time. The PI3K-δ inhibitor idelalisib is selective for PI3K-δ with a longer residence time and higher on-rate than for the other isoforms of PI3K. The pan-PI3K inhibitor buparlisib is not selective for a specific isoform.</p> </div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-7 fusion_builder_column_1_3 1_3 fusion-flex-column" style="--awb-bg-size:cover;--awb-border-color:#dddddd;--awb-border-top:1px;--awb-border-right:1px;--awb-border-bottom:1px;--awb-border-left:1px;--awb-border-style:solid;--awb-width-large:33.333333333333%;--awb-margin-top-large:0px;--awb-spacing-right-large:5.76%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:5.76%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-image-element " style="--awb-max-width:400px;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);"><span class=" fusion-imageframe imageframe-none imageframe-2 hover-type-none"><a href="https://www.oncolines.com/wp-content/uploads/2020/06/ResidenceTimer_PI3K-overlays.png" class="fusion-lightbox" data-rel="iLightbox[3a60b9fe99ccf3062c2]" data-title="ResidenceTimer PI3K Overlays" title="Overlay Of Binding Curves For The PI3K Inhibitor Idelalisib"><img decoding="async" width="588" height="490" alt="ResidenceTimer_PI3K overlays" src="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-idelalisib-.png" data-orig-src="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-idelalisib-.png" class="lazyload img-responsive wp-image-4414" srcset="data:image/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27588%27%20height%3D%27490%27%20viewBox%3D%270%200%20588%20490%27%3E%3Crect%20width%3D%27588%27%20height%3D%27490%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E" data-srcset="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-idelalisib--200x167.png 200w, https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-idelalisib--400x333.png 400w, https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-idelalisib-.png 588w" data-sizes="auto" data-orig-sizes="(max-width: 1024px) 100vw, (max-width: 640px) 100vw, 400px" /></a></span></div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-8 fusion_builder_column_1_3 1_3 fusion-flex-column" style="--awb-bg-size:cover;--awb-border-color:#dddddd;--awb-border-top:1px;--awb-border-right:1px;--awb-border-bottom:1px;--awb-border-left:1px;--awb-border-style:solid;--awb-width-large:33.333333333333%;--awb-margin-top-large:0px;--awb-spacing-right-large:5.76%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:5.76%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-image-element " style="--awb-max-width:400px;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);"><span class=" fusion-imageframe imageframe-none imageframe-3 hover-type-none"><a href="https://www.oncolines.com/wp-content/uploads/2020/06/ResidenceTimer_PI3K-overlays.png" class="fusion-lightbox" data-rel="iLightbox[3a60b9fe99ccf3062c2]" data-title="ResidenceTimer PI3K Overlays" title="Overlay Of Binding Curves For The PI3K Inhibitor Duvelisib"><img decoding="async" width="588" height="490" alt="ResidenceTimer_PI3K overlays" src="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-duvelisib.png" data-orig-src="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-duvelisib.png" class="lazyload img-responsive wp-image-4411" srcset="data:image/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27588%27%20height%3D%27490%27%20viewBox%3D%270%200%20588%20490%27%3E%3Crect%20width%3D%27588%27%20height%3D%27490%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E" data-srcset="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-duvelisib-200x167.png 200w, https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-duvelisib-400x333.png 400w, https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-duvelisib.png 588w" data-sizes="auto" data-orig-sizes="(max-width: 1024px) 100vw, (max-width: 640px) 100vw, 400px" /></a></span></div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-9 fusion_builder_column_1_3 1_3 fusion-flex-column" style="--awb-bg-size:cover;--awb-border-color:#dddddd;--awb-border-top:1px;--awb-border-right:1px;--awb-border-bottom:1px;--awb-border-left:1px;--awb-border-style:solid;--awb-width-large:33.333333333333%;--awb-margin-top-large:0px;--awb-spacing-right-large:5.76%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:5.76%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-image-element " style="--awb-max-width:400px;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);"><span class=" fusion-imageframe imageframe-none imageframe-4 hover-type-none"><a href="https://www.oncolines.com/wp-content/uploads/2020/06/ResidenceTimer_PI3K-overlays.png" class="fusion-lightbox" data-rel="iLightbox[3a60b9fe99ccf3062c2]" data-title="ResidenceTimer PI3K Overlays" title="Overlay Of Binding Curves For The PI3K Inhibitor Buparlisib"><img decoding="async" width="588" height="490" alt="ResidenceTimer_PI3K overlays" src="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-buparlisib.png" data-orig-src="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-buparlisib.png" class="lazyload img-responsive wp-image-4410" srcset="data:image/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27588%27%20height%3D%27490%27%20viewBox%3D%270%200%20588%20490%27%3E%3Crect%20width%3D%27588%27%20height%3D%27490%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E" data-srcset="https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-buparlisib-200x167.png 200w, https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-buparlisib-400x333.png 400w, https://www.oncolines.com/wp-content/uploads/2020/06/Overlay-of-binding-curves-for-the-PI3K-inhibitors-buparlisib.png 588w" data-sizes="auto" data-orig-sizes="(max-width: 1024px) 100vw, (max-width: 640px) 100vw, 400px" /></a></span></div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-10 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-padding-top:1em;--awb-padding-right:4%;--awb-padding-bottom:1em;--awb-padding-left:4%;--awb-bg-color:var(--awb-color3);--awb-bg-color-hover:var(--awb-color3);--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:4%;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-text fusion-text-4"><h6>Binding curve overlays for the inhibitors idelalisib (PI3K-δ inhibitor), duvelisib (PI3K-γ/δ inhibitor) and buparlisib (pan-PI3K inhibitor) (<a title="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587" href="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587" target="_blank" rel="noopener noreferrer">Willemsen-Seegers <em>et al.</em>, 2017</a>)</h6> </div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-11 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-title title fusion-title-5 sep-underline sep-solid fusion-title-text fusion-title-size-two"><h2 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:17.25;--minFontSize:17.25;line-height:2;">SPR and Cell-Based Data Together Provide a Hypothesis on the Mechanism of Action <em>In Vivo</em></h2></div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-12 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-padding-right:14px;--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-text fusion-text-5"><p>The pharmacological behaviour of selective PI3K inhibitors was confirmed in cell-based assays. Selective and pan-PI3K inhibitors were profiled in the cancer cell line panel <a title="link to website Oncolines™" href="https://www.oncolines.com/" target="_blank" rel="noopener noreferrer">Oncolines®</a> via proliferation assays. The IC<sub>50</sub> fingerprints of the PI3K inhibitors (over the full panel) were compared to the IC<sub>50 </sub>fingerprints of 120 anticancer agents. As part of the comparative analysis, compounds with similar IC<sub>50</sub> fingerprints were clustered. The clustering showed that selective PI3K inhibitors cluster separately from pan-PI3K inhibitors (<a title="https://mct.aacrjournals.org/content/early/2016/09/01/1535-7163.MCT-16-0403" href="https://mct.aacrjournals.org/content/early/2016/09/01/1535-7163.MCT-16-0403" target="_blank" rel="noopener noreferrer">Uitdehaag <em>et al.</em>, 2016</a>).</p> </div><div class="fusion-separator fusion-full-width-sep" style="align-self: center;margin-left: auto;margin-right: auto;margin-top:2px;width:100%;"></div><ul style="--awb-iconcolor:var(--awb-color5);--awb-line-height:27.2px;--awb-icon-width:27.2px;--awb-icon-height:27.2px;--awb-icon-margin:11.2px;--awb-content-margin:38.4px;--awb-circlecolor:var(--awb-custom_color_4);--awb-circle-yes-font-size:14.08px;" class="fusion-checklist fusion-checklist-2 fusion-checklist-default type-icons"><li class="fusion-li-item" style=""><span class="icon-wrapper circle-yes"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>SPR and cell-based data together provide a hypothesis on the mechanism of action <i>in vivo</i></p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-yes"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>More information on Oncolines® and the comparative analysis of IC<sub>50</sub> data:</p> <div class="fusion-button-wrapper"><a class="fusion-button button-flat fusion-button-default-size button-custom fusion-button-default button-2 fusion-button-default-span fusion-button-default-type" style="--button_accent_color:#ffffff;--button_accent_hover_color:#ffffff;--button_border_hover_color:#ffffff;--button_gradient_top_color:var(--awb-custom_color_2);--button_gradient_bottom_color:var(--awb-custom_color_2);--button_gradient_top_color_hover:var(--awb-color5);--button_gradient_bottom_color_hover:var(--awb-color5);" target="_blank" rel="noopener noreferrer" title="Link to Oncolines" aria-label="Link to Oncolines" href="https://www.oncolines.com/oncolines/oncolines-explained-facts/"><i class="fa-sign-out-alt fas button-icon-left" aria-hidden="true"></i><span class="fusion-button-text">oncolines</span></a></div> </div></li></ul></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-13 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-padding-top:4%;--awb-padding-right:4%;--awb-padding-bottom:4%;--awb-padding-left:4%;--awb-bg-color:var(--awb-color3);--awb-bg-color-hover:var(--awb-color3);--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-image-element " style="--awb-max-width:600px;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);"><span class=" fusion-imageframe imageframe-none imageframe-5 hover-type-none" style="border:1px solid #dddddd;"><img decoding="async" width="1008" height="878" alt=" Oncolines™ network tree of PI3K inhibitors" title="Oncolines™ Network Tree Of PI3K Inhibitors" src="https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2.png" data-orig-src="https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2.png" class="lazyload img-responsive wp-image-5092" srcset="data:image/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%271008%27%20height%3D%27878%27%20viewBox%3D%270%200%201008%20878%27%3E%3Crect%20width%3D%271008%27%20height%3D%27878%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E" data-srcset="https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2-200x174.png 200w, https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2-400x348.png 400w, https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2-600x523.png 600w, https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2-800x697.png 800w, https://www.oncolines.com/wp-content/uploads/2020/07/Oncolines™-network-tree-of-PI3K-inhibitors_v2.png 1008w" data-sizes="auto" data-orig-sizes="(max-width: 1024px) 100vw, (max-width: 640px) 100vw, 600px" /></span></div><div class="fusion-text fusion-text-6"><h6>Oncolines® network tree of PI3K inhibitors. Connections are drawn between compounds with a defined correlation. Only compounds within two connections of the investigated compounds (red) are shown (<a title="https://mct.aacrjournals.org/content/early/2016/09/01/1535-7163.MCT-16-0403" href="https://mct.aacrjournals.org/content/early/2016/09/01/1535-7163.MCT-16-0403" target="_blank" rel="noopener noreferrer">Uitdehaag <em>et al</em>., 2016</a>). The network tree shows that the PI3K inhibitors are separated into two clusters, the first containing alpelisib, buparlisib, pictilisib, and apitolisib, the second containing duvelisib, idelalisib, and TGX-221. Interestingly, buparlisib, the most advanced pan-PI3K inhibitor in the clinic (<a title="https://mct.aacrjournals.org/content/13/5/1021" href="https://mct.aacrjournals.org/content/13/5/1021" target="_blank" rel="noopener noreferrer">Dienstmann <em>et al.</em>, 2014</a>) shows correlation with a substantial number of profiles of non-PI3K inhibitors.</h6> </div></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-5 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:calc( 1100px + 0px );margin-left: calc(-0px / 2 );margin-right: calc(-0px / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-14 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:0px;--awb-margin-bottom-large:20px;--awb-spacing-left-large:0px;--awb-width-medium:100%;--awb-spacing-right-medium:0px;--awb-spacing-left-medium:0px;--awb-width-small:100%;--awb-spacing-right-small:0px;--awb-spacing-left-small:0px;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-title title fusion-title-6 sep-underline sep-solid fusion-title-text fusion-title-size-one"><h1 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:27;line-height:1.2;">Distinction by On- and Off-Rates</h1></div><div class="fusion-text fusion-text-7"><p>Compounds may have similar affinity for a target while the association and dissociation rates of the drugs can differ. The figure below shows Aurora inhibitors with similar affinities for Aurora A and Aurora B (<a title="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587" href="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587" target="_blank" rel="noopener noreferrer">Willemsen-Seegers <em>et al.,</em> 2017</a>). Practically all inhibitors have affinities between 1 and 10 nM. Despite the comparable affinities, the figure shows that the association and dissociation kinetics of the compounds on Aurora A and B are clearly distinctive. The pan-Aurora inhibitor danusertib has similar affinity for Aurora A and B as shown in the table, while it has a 14-fold lower dissociation rate for Aurora B. This means that danusertib has much longer target residence time on Aurora B than Aurora A. In this context, it should also be noted that danusertib behaves as an Aurora B inhibitor in cell-based assays (<a title="https://mct.aacrjournals.org/content/6/12/3158" href="https://mct.aacrjournals.org/content/6/12/3158" target="_blank" rel="noopener noreferrer">Carpinelli <em>et al</em>., 2007</a>). Especially for compounds of which the target residence time measurement exceeds the half-life in circulation, kinetic selectivity is more predictive for <i>in vivo</i> effect than determining selectivity on the basis of IC<sub>50</sub> or <em>K</em><sub>D</sub>.</p> </div></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-6 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-padding-top:4%;--awb-padding-right:4%;--awb-padding-bottom:1em;--awb-padding-left:4%;--awb-background-color:var(--awb-color3);--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:1144px;margin-left: calc(-4% / 2 );margin-right: calc(-4% / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-15 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-image-element " style="--awb-max-width:500px;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);"><span class=" fusion-imageframe imageframe-none imageframe-6 hover-type-none"><a href="https://www.oncolines.com/wp-content/uploads/2020/07/ResidenceTimer_AurAB-plot_v2-1.png" class="fusion-lightbox" data-rel="iLightbox[95544b90f66b178774d]" data-title="Plot Of Association Rates (x Axis) And Dissociation Rates (y Axis) For Aurora Inhibitors" title="Plot Of Association Rates (x Axis) And Dissociation Rates (y Axis) For Aurora Inhibitors"><img decoding="async" width="1100" height="767" alt="Plot Of Association Rate (x Axis) And Dissociation Rate (y Axis) Of Aurora Kinase Inhibitors" src="data:image/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%271100%27%20height%3D%27767%27%20viewBox%3D%270%200%201100%20767%27%3E%3Crect%20width%3D%271100%27%20height%3D%27767%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E" data-orig-src="https://www.oncolines.com/wp-content/uploads/2020/07/ResidenceTimer_AurAB-plot_v2-1.png" class="lazyload img-responsive wp-image-4884"/></a></span></div></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-16 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"> <div class="table-1"> <table width="100%"> <tbody> <tr> <td align="left"><strong>danusertib</strong></td> <td align="left"><strong><em>K</em><sub>D </sub>(M)</strong></td> <td align="left"><strong><em>k</em><sub>d</sub> (s<sup>-1</sup>)</strong></td> </tr> <tr> <td align="left">Aurora A</td> <td align="left">1.69E-09</td> <td align="left">8.68E-04</td> </tr> <tr> <td align="left">Aurora B</td> <td align="left">1.44E-09</td> <td align="left">6.26E-05</td> </tr> </tbody> </table> </div> <div class="fusion-separator fusion-full-width-sep" style="align-self: center;margin-left: auto;margin-right: auto;margin-top:2em;width:100%;"></div><div class="fusion-text fusion-text-8"><h6><strong>Left</strong>: Plot of association rate (x-axis) and dissociation rate (y-axis) of Aurora kinase inhibitors. Dotted lines refer to equilibrium affinity constants (<em>K</em><sub>D</sub>) calculated from the on- and off rates (<a title="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587" href="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587" target="_blank" rel="noopener noreferrer">Willemsen-Seegers et al., 2017</a>).<br /> <strong>Above</strong>: Affinity and dissociation rate of danusertib on Aurora A and B. Kinetic constants are averages of logarithmic values.</h6> </div></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-7 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:1144px;margin-left: calc(-4% / 2 );margin-right: calc(-4% / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-17 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-separator fusion-full-width-sep" style="align-self: center;margin-left: auto;margin-right: auto;margin-top:2em;width:100%;"></div><ul style="--awb-iconcolor:var(--awb-color5);--awb-line-height:27.2px;--awb-icon-width:27.2px;--awb-icon-height:27.2px;--awb-icon-margin:11.2px;--awb-content-margin:38.4px;" class="fusion-checklist fusion-checklist-3 fusion-checklist-default type-icons"><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Measuring kinetic selectivity within a family of targets</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Highlighting differences in on- and off-rates</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Providing a hypothesis on pharmacological behaviour <i>in vivo</i></p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Uniform immobilization of targets on the Biacore chip</p> </div></li></ul></div></div><div class="fusion-layout-column fusion_builder_column fusion-builder-column-18 fusion_builder_column_1_2 1_2 fusion-flex-column" style="--awb-bg-size:cover;--awb-width-large:50%;--awb-margin-top-large:0px;--awb-spacing-right-large:3.84%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:3.84%;--awb-width-medium:100%;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-separator fusion-full-width-sep" style="align-self: center;margin-left: auto;margin-right: auto;margin-top:2em;width:100%;"></div><ul style="--awb-iconcolor:var(--awb-color5);--awb-line-height:27.2px;--awb-icon-width:27.2px;--awb-icon-height:27.2px;--awb-icon-margin:11.2px;--awb-content-margin:38.4px;" class="fusion-checklist fusion-checklist-4 fusion-checklist-default type-icons"><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Parallel experiments to compare results across targets</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Compound affinity measured in the absence of ATP and substrate</p> </div></li><li class="fusion-li-item" style=""><span class="icon-wrapper circle-no"><i class="fusion-li-icon fa-dot-circle fas" aria-hidden="true"></i></span><div class="fusion-li-item-content"> <p>Enzyme-inhibitor interactions studied in an open system, better resembling <i>in vivo</i> situations than an assay in equilibrium, or end-point assay</p> </div></li></ul></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-8 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-margin-top:1em;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:calc( 1100px + 0px );margin-left: calc(-0px / 2 );margin-right: calc(-0px / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-19 fusion_builder_column_1_1 1_1 fusion-flex-column" style="--awb-padding-top:1.5em;--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:0px;--awb-margin-bottom-large:20px;--awb-spacing-left-large:0px;--awb-width-medium:100%;--awb-spacing-right-medium:0px;--awb-spacing-left-medium:0px;--awb-width-small:100%;--awb-spacing-right-small:0px;--awb-spacing-left-small:0px;"><div class="fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column"><div class="fusion-title title fusion-title-7 sep-underline sep-solid fusion-title-text fusion-title-size-two"><h2 class="fusion-title-heading title-heading-left fusion-responsive-typography-calculated" style="margin:0;--fontSize:17.25;--minFontSize:17.25;line-height:2;">References</h2></div><div class="fusion-text fusion-text-9"><p><a href="https://doi.org/10.1093/annonc/mdv293">Maia <em>et al.</em> (2015)</a> <em>Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model.</em> Annals of Oncology, 26 (10):2180-2192.</p> <p><a href="https://www.sciencedirect.com/science/article/abs/pii/S0022283616305587">Willemsen-Seegers <em>et al.</em> (2017)</a> <em>Compound Selectivity and Target Residence Time of Kinase Inhibitors Studied with Surface Plasmon Resonance.</em> Journal of Molecular Biology, 429:574-586.</p> <p><a href="http://mct.aacrjournals.org/content/early/2016/09/01/1535-7163.MCT-16-0403">Uitdehaag <em>et al.</em> (2016)</a> <em>Cell Panel Profiling Reveals Conserved Therapeutic Clusters and Differentiates the Mechanism of Action of Different PI3K/mTOR, Aurora Kinase and EZH2 Inhibitors</em>. Molecular Cancer Therapeutics, 15 (12):3097-3109.</p> <p><a href="https://mct.aacrjournals.org/content/13/5/1021">Dienstmann<em> et al.</em> (2014)</a> <em>Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors</em>. Molecular Cancer Therapeutics, 13 (5):1021-1031.</p> <p><a href="https://mct.aacrjournals.org/content/6/12/3158">Carpinelli <em>et al.</em> (2007)</a> <em>PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer</em>. Molecular Cancer Therapeutics, 6 (12):3158-3168.</p> </div></div></div></div></div><div class="fusion-fullwidth fullwidth-box fusion-builder-row-9 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling" style="--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;" ><div class="fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap" style="max-width:calc( 1100px + 0px );margin-left: calc(-0px / 2 );margin-right: calc(-0px / 2 );"><div class="fusion-layout-column fusion_builder_column fusion-builder-column-20 fusion_builder_column_1_1 1_1 fusion-flex-column" 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