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  <front>
    <journal-meta>
      <journal-id journal-id-type="iso-abbrev">Pharmacophore</journal-id>
      <journal-id journal-id-type="publisher-id">pharmacophorejournal.com</journal-id>
      <journal-id journal-id-type="publisher-id">Pharmacophore</journal-id>
      <journal-title-group>
        <journal-title>Pharmacophore</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2229-5402</issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">pharmacophorejournal.com-6925</article-id>
      <article-id pub-id-type="doi">10.51847/QdjN456XBW</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>What Makes an Artificial Intelligence Explanation Pharmacologically Useful beyond Attractive Heatmaps and Feature-Importance Rankings?</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Morales</surname>
                <given-names>Sofia</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Kumar</surname>
                <given-names>Naveen</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Georgiou</surname>
                <given-names>Elena</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Garcia</surname>
                <given-names>Carlos</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Pharmacologically Useful Explainability, Faculty of Pharmacy, National University of La Plata, La Plata, Argentina.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Explanation Validity and Biological Relevance, Faculty of Pharmacy, Indian Agricultural Research Institute, New Delhi, India.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Beyond-Heatmap Interpretation, Faculty of Pharmaceutical Sciences, University of Patras, Patras, Greece.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Feature-Importance and Decision Utility, Faculty of Pharmacy, Polytechnic University of Valencia, Valencia, Spain.
          </aff>
                          <author-notes>
            <corresp id="cor1">
              <bold>Address for correspondence:</bold> Prof. Wael Abu Dayyih, Department of
              Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan.
                              E-mail: <email xlink:href="sofia.morales@agro.unlp.edu.ar">sofia.morales@agro.unlp.edu.ar</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>12</month>
        <year>2024</year>
      </pub-date>
      <volume>15</volume>
      <issue>6</issue>
      <fpage>76</fpage>
      <lpage>86</lpage>
      <permissions>
        <copyright-statement>
          Copyright: &#x000a9; 2026 Pharmacophore
        </copyright-statement>
        <copyright-year>2026</copyright-year>
        <license>
          <ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/"
            specific-use="textmining" content-type="ccbyncsalicense">
            https://creativecommons.org/licenses/by-nc-sa/4.0/</ali:license_ref>
          <license-p>This is an open access journal, and articles are distributed under the terms of
            the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
            others to remix, tweak, and build upon the work non-commercially, as long as appropriate
            credit is given and the new creations are licensed under the identical terms.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>A<sc>BSTRACT</sc></title>
        <p>Artificial intelligence explanations are increasingly presented in pharmaceutical research as molecular saliency maps, ranked descriptors, pathway-level importance scores, covariate effects, counterfactual examples, and local prediction narratives. Although these outputs can make model behaviour more visible, visibility alone does not establish that an explanation is pharmacologically meaningful, scientifically dependable, or suitable for influencing a development decision. This article addresses the unresolved distinction between visually interpretable model output and pharmacologically useful explanation. It develops a proposed explanation-evaluation theory in which usefulness is defined relationally: an explanation must answer a specified scientific question for an identified user, support a bounded pharmaceutical decision, remain faithful to the model being interpreted, demonstrate context-appropriate stability, align cautiously with relevant chemical, biological, or pharmacometric knowledge, and communicate uncertainty without converting association into mechanism or prediction into experimental confirmation. The central contribution is the proposed Pharmacological Usefulness Test for AI Explanations, a non-compensatory evaluation construct in which visual attractiveness, predictive performance, user satisfaction, or apparent mechanistic plausibility cannot offset failure in a critical evidentiary dimension. The theory is designed to support comparative evaluation across molecular, omics, and pharmacometric models while preserving domain-specific evidence requirements. It also identifies failure modes arising from unstable attribution, inappropriate explanatory questions, mechanistic overinterpretation, uncalibrated confidence, automation bias, and insufficient human contestability. The proposed test is conceptual rather than empirically validated and does not establish clinical utility, regulatory acceptability, universal thresholds, or deployment readiness. Its intended value is to organize future explanation studies around pharmaceutical questions, evidentiary boundaries, and decision consequences rather than the persuasive appearance of explanatory graphics.</p>
      </abstract>
      <kwd-group>
                <kwd>Explainable artificial intelligence</kwd>
                <kwd>Computational pharmacology</kwd>
                <kwd>Drug discovery</kwd>
                <kwd>Pharmacometrics</kwd>
                <kwd>Mechanism alignment</kwd>
                <kwd>Explanation faithfulness</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>