{"id":524682,"date":"2022-12-09T22:10:06","date_gmt":"2022-12-09T19:10:06","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/surprise-discovery-set-to-improve-drug-development\/"},"modified":"2022-12-09T22:10:06","modified_gmt":"2022-12-09T19:10:06","slug":"surprise-discovery-set-to-improve-drug-development","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/surprise-discovery-set-to-improve-drug-development\/","title":{"rendered":"#Surprise discovery set to improve drug development"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_84 counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of Contents<\/p>\n<label for=\"ez-toc-cssicon-toggle-item-6a2ebe01c4ed5\" class=\"ez-toc-cssicon-toggle-label\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #dd3333;color:#dd3333\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #dd3333;color:#dd3333\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/label><input type=\"checkbox\"  id=\"ez-toc-cssicon-toggle-item-6a2ebe01c4ed5\" checked aria-label=\"Toggle\" \/><nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-1'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/buradabiliyorum.com\/en\/surprise-discovery-set-to-improve-drug-development\/#%E2%80%9CSurprise_discovery_set_to_improve_drug_development%E2%80%9D\" >&#8220;Surprise discovery set to improve drug development&#8221;<\/a><\/li><\/ul><\/nav><\/div>\n<h1><span class=\"ez-toc-section\" id=\"%E2%80%9CSurprise_discovery_set_to_improve_drug_development%E2%80%9D\"><\/span>&#8220;Surprise discovery set to improve drug development&#8221;<span class=\"ez-toc-section-end\"><\/span><\/h1>\n<div>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2022\/surprise-discovery-set.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2022\/surprise-discovery-set.jpg\" data-sub-html=\"Ketoprofen binding sites in HSA (PDB entry &lt;a href=&quot;http:\/\/scripts.iucr.org\/cgi-bin\/cr.cgi?rm=pdb&amp;amp;pdbId=7jwn&quot;&gt;7jwn&lt;\/a&gt;). The 2&lt;i&gt;mF&lt;\/i&gt;&lt;sub&gt;o&lt;\/sub&gt; \u2212 &lt;i&gt;DF&lt;\/i&gt;&lt;sub&gt;c&lt;\/sub&gt; electron-density map (r.m.s.d. of 1.0\u2005\u00c5) is presented in blue and the &lt;i&gt;mF&lt;\/i&gt;&lt;sub&gt;o&lt;\/sub&gt; \u2212 &lt;i&gt;DF&lt;\/i&gt;&lt;sub&gt;c&lt;\/sub&gt; omit electron-density map (map calculated after ten &lt;i&gt;REFMAC&lt;\/i&gt; refinement cycles without the drug in the model, r.m.s.d. of 2.5\u2005\u00c5) is presented in green. Ketoprofen molecules are shown in stick representation with O atoms in red and C atoms in yellow. Credit: &lt;i&gt;IUCrJ&lt;\/i&gt; (2022). DOI: 10.1107\/S2052252522006820\">\n<figure class=\"article-img\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/scx1.b-cdn.net\/csz\/news\/800a\/2022\/surprise-discovery-set.jpg\" alt=\"Surprise discovery set to improve drug development\" title=\"Ketoprofen binding sites in HSA (PDB entry &lt;a href=&quot;http:\/\/scripts.iucr.org\/cgi-bin\/cr.cgi?rm=pdb&amp;amp;pdbId=7jwn&quot;&gt;7jwn&lt;\/a&gt;). The 2&lt;i&gt;mF&lt;\/i&gt;&lt;sub&gt;o&lt;\/sub&gt; \u2212 &lt;i&gt;DF&lt;\/i&gt;&lt;sub&gt;c&lt;\/sub&gt; electron-density map (r.m.s.d. of 1.0\u2005\u00c5) is presented in blue and the &lt;i&gt;mF&lt;\/i&gt;&lt;sub&gt;o&lt;\/sub&gt; \u2212 &lt;i&gt;DF&lt;\/i&gt;&lt;sub&gt;c&lt;\/sub&gt; omit electron-density map (map calculated after ten &lt;i&gt;REFMAC&lt;\/i&gt; refinement cycles without the drug in the model, r.m.s.d. of 2.5\u2005\u00c5) is presented in green. Ketoprofen molecules are shown in stick representation with O atoms in red and C atoms in yellow. Credit: &lt;i&gt;IUCrJ&lt;\/i&gt; (2022). DOI: 10.1107\/S2052252522006820\" width=\"640\" height=\"530\"\/><figcaption class=\"text-darken text-low-up text-truncate-js text-truncate mt-3\">\n                Ketoprofen binding sites in HSA (PDB entry <a rel=\"nofollow noopener\" target=\"_blank\" href=\"http:\/\/scripts.iucr.org\/cgi-bin\/cr.cgi?rm=pdb&amp;pdbId=7jwn\">7jwn<\/a>). The 2<i>mF<\/i><sub>o<\/sub> \u2212 <i>DF<\/i><sub>c<\/sub> electron-density map (r.m.s.d. of 1.0\u2005\u00c5) is presented in blue and the <i>mF<\/i><sub>o<\/sub> \u2212 <i>DF<\/i><sub>c<\/sub> omit electron-density map (map calculated after ten <i>REFMAC<\/i> refinement cycles without the drug in the model, r.m.s.d. of 2.5\u2005\u00c5) is presented in green. Ketoprofen molecules are shown in stick representation with O atoms in red and C atoms in yellow. Credit: <i>IUCrJ<\/i> (2022). DOI: 10.1107\/S2052252522006820<br \/>\n            <\/figcaption><\/figure>\n<\/div>\n<\/div>\n<p>A surprising discovery from the University of Virginia School of Medicine has torpedoed a key principle used in the development of new drugs to treat diseases. The finding could speed the drug-development process and help prevent potentially harmful drug interactions.<\/p>\n<section class=\"article-banner first-banner ads-336x280\"><!-- \/4988204\/Phys_Story_InText_Box --><br \/>\n      <\/section>\n<p>The new research from UVA&#8217;s Wladek Minor, Ph.D., and collaborators calls into question an <a href=\"https:\/\/buradabiliyorum.com\/en\/category\/download-scripts-themes-apps\/\" data-internallinksmanager029f6b8e52c=\"9\" title=\"Download Scripts &amp; Themes &amp; Apps\" target=\"_blank\" rel=\"noopener\">app<\/a>roach commonly used in drug development. Until now, scientists assumed that an important drug transporter in the blood, a protein called albumin, behaves similarly to lab models widely used in drug development as it will in human blood. But Minor&#8217;s new work demonstrates that&#8217;s not necessarily the case.<\/p>\n<p>&#8220;Our unexpected findings should be of special interest to people studying [biological processes called] protein-ligand interactions and for scientists performing pre-clinical research in drug discovery,&#8221; said Minor, Harrison Distinguished Professor in UVA&#8217;s Department of Molecular Physiology and Biological Physics. &#8220;The cross-drug interaction is often discovered during clinical trials and sometimes only when new medicines are on the pharmacy shelves.&#8221; <\/p>\n<p>Alan Stewart, Ph.D., a co-author of the study at the University of St Andrews in the United Kingdom, said the findings offer important guidance for developing safer drugs. &#8220;This work directly demonstrates that drugs can be carried differently around the body across mammals and highlights a need for caution when using non-human albumins or animal models in drug development,&#8221; he said.<\/p>\n<p><b>Drug development insights<\/b><\/p>\n<p>Serum albumin is made in the liver and serves many important functions in the body, including maintaining the proper distribution of bodily fluids in tissues. It&#8217;s an important delivery vehicle, picking up substances such as hormones, fatty acids and drugs and ferrying them through the blood to where they are needed.<\/p>\n<p>Serum albumin is found not just in humans but in mammals <a href=\"https:\/\/buradabiliyorum.com\/en\/category\/general\/\" data-internallinksmanager029f6b8e52c=\"3\" title=\"General\" target=\"_blank\" rel=\"noopener\">general<\/a>ly. As such, scientists often rely on non-human albumins, such as bovine albumin from cattle, and on animal models, such as lab mice, to predict how albumin will interact with drugs in human patients. But Minor&#8217;s new work points out unexpected pitfalls of that practice.<\/p>\n<p>Minor and his team looked at how a common nonsteroidal anti-inflammatory drug (NSAID), ketoprofen, interacted with both human albumin and other mammalian albumins. They discovered that these interactions were quite inconsistent, with different albumins binding with the drug in different locations. That suggests that assumptions drawn from the mammalian albumins might not produce reliable results for developing drugs for humans.<\/p>\n<p>&#8220;A deeper understanding of drug transport by plasma proteins, its potential variability across species and patients, and implications for drug-drug interactions will definitely facilitate small-molecule drug discovery and ultimately benefit patients,&#8221; said Ivan Shabalin, Ph.D., an alumnus of Minor&#8217;s lab now working on a precision-medicine approach to oncology therapeutics at IDEAYA Bio<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/sciencee\/\" data-internallinksmanager029f6b8e52c=\"5\" title=\"Science\" target=\"_blank\" rel=\"noopener\">science<\/a>s in San Francisco.<\/p>\n<p>Based on their findings, Minor and his collaborators are calling for additional studies scrutinizing how other drugs bind with albumin. Moving forward, they say, it will be essential for scientists to assess the suitability of particular albumins for their research. This understanding will help them better predict how human albumin will bind with the drugs and reduce the risk of unexpected and unwanted drug interactions.<\/p>\n<p>&#8220;This research shows that when we are getting unexpected results, we need to dig deeply to understand them and their consequences. Advanced biomedical research often requires transdisciplinary collaboration of scientists with disparate backgrounds and perspectives to address complex research questions,&#8221; Minor said. &#8220;We hope that this work will help researchers understand the limitations of pharmacological studies aimed at treating humans but that are based on other organisms.&#8221;<\/p>\n<p>The researchers have published their findings in <i>IUCrJ<\/i>. The paper was accompanied by an editorial highlighting the work&#8217;s importance and was featured on the journal&#8217;s cover. The research team consisted of Mateusz P. Czub (a UVA Ph.D. recipient now at Paul Sherer Institute in Switzerland), Stewart, Shabalin and Minor.<\/p>\n<div class=\"article-main__more p-4\">\n                                                                                        <strong>More information:<\/strong><br \/>\n                                                Mateusz P. Czub et al, Organism-specific differences in the binding of ketoprofen to serum albumin, <i>IUCrJ<\/i> (2022).  <a rel=\"nofollow noopener\" target=\"_blank\" data-doi=\"1\" href=\"https:\/\/dx.doi.org\/10.1107\/S2052252522006820\">DOI: 10.1107\/S2052252522006820<\/a><\/p>\n<\/div>\n<div class=\"d-inline-block text-medium mt-4\">\n<p>\n                                                    Provided by<br \/>\n                                                                                                            University of Virginia<br \/>\n                                                                                                                <a rel=\"nofollow noopener\" target=\"_blank\" class=\"icon_open\" href=\"http:\/\/www.virginia.edu\/\"><br \/>\n                                                            <svg><use href=\"https:\/\/phys.b-cdn.net\/tmpl\/v6\/img\/svg\/sprite.svg#icon_open\" x=\"0\" y=\"0\"\/><\/svg><\/a><\/p><\/div>\n<p>                                        <!-- print only --><\/p>\n<div class=\"d-none d-print-block\">\n<p>                                                    <strong>Citation<\/strong>:<br \/>\n                                                    Surprise discovery set to improve drug development (2022, December  9)<br \/>\n                                                    retrieved 10 December 2022<br \/>\n                                                    from https:\/\/phys.org\/<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/news\/\" data-internallinksmanager029f6b8e52c=\"2\" title=\"News\" target=\"_blank\" rel=\"noopener\">news<\/a>\/2022-12-discovery-drug.html<\/p>\n<p>                                             This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no<br \/>\n                                             part may be reproduced without the written permission. The content is provided for information purposes only.<\/p><\/div>\n<\/p><\/div>\n<p><script id=\"facebook-jssdk\" async=\"\" src=\"https:\/\/connect.facebook.net\/en_US\/sdk.js\"><\/script><\/p>\n<blockquote><p><strong><span style=\"color: #ff6600;\">If you liked the article, do not forget to share it with your friends. Follow us on\u00a0<span style=\"color: #ff0000;\"><a style=\"color: #ff0000;\" href=\"https:\/\/news.google.com\/publications\/CAAqBwgKMLG0nwswvr63Aw\" target=\"_blank\" rel=\"nofollow noopener noreferrer\">Google News<\/a><\/span>\u00a0too, click on the star and choose us from your favorites.<\/span><\/strong><\/p><\/blockquote>\n<blockquote>\n<p style=\"text-align: center;\">For forums sites go to <span style=\"color: #ff9900;\"><a style=\"color: #ff9900;\" href=\"https:\/\/forum.buradabiliyorum.com\/\" target=\"_blank\" rel=\"noopener\">Forum.BuradaBiliyorum.Com<\/a><\/span><\/strong>\n<\/p><\/blockquote>\n<blockquote>\n<p style=\"text-align: center;\"><strong>If you want to read more Like this articles, you can visit our <span style=\"color: #ff9900;\"><a style=\"color: #ff9900;\" href=\"https:\/\/en.buradabiliyorum.com\/science\/\" target=\"_blank\" rel=\"noopener\">Science category.<\/a><\/span><\/strong><\/p>\n<\/blockquote>\n<p><span style=\"color: black;\"><a style=\"color: #ff9900;\" href=\"https:\/\/phys.org\/news\/2022-12-discovery-drug.html\" target=\"_blank\" rel=\"noopener\">Source<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Surprise discovery set to improve drug development&#8221; Ketoprofen binding sites in HSA (PDB entry 7jwn). The 2mFo \u2212 DFc electron-density map (r.m.s.d. of 1.0\u2005\u00c5) is presented in blue and the mFo \u2212 DFc omit electron-density map (map calculated after ten REFMAC refinement cycles without the drug in the model, r.m.s.d. of 2.5\u2005\u00c5) is presented in&#8230;<\/p>\n","protected":false},"author":1,"featured_media":524683,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"fifu_image_url":"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2022\/surprise-discovery-set.jpg","fifu_image_alt":"","footnotes":""},"categories":[16],"tags":[],"class_list":["post-524682","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sciencee"],"_links":{"self":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/524682","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/comments?post=524682"}],"version-history":[{"count":0,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/524682\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media\/524683"}],"wp:attachment":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media?parent=524682"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/categories?post=524682"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/tags?post=524682"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}