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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-6915</article-id>
      <article-id pub-id-type="doi">10.51847/2zdDmj0iLu</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Where Artificial Intelligence Changes Drug Discovery—and Where It Does Not: A Critical Review of Evidence, Limitations, and Translational Value</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Williams</surname>
                <given-names>Sophie</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Rodriguez</surname>
                <given-names>Javier</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Vries</surname>
                <given-names>Elena De</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of AI in Drug Discovery and Critical Appraisal, Faculty of Pharmaceutical Sciences, University of Amsterdam, Amsterdam, Netherlands.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Translational Value and Evidence Assessment, Faculty of Pharmacy, University of Aruba, Oranjestad, Aruba.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of AI Limitations and Scientific Reasoning, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
          </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="sophie.williams@uva.nl">sophie.williams@uva.nl</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>10</month>
        <year>2024</year>
      </pub-date>
      <volume>15</volume>
      <issue>5</issue>
      <fpage>27</fpage>
      <lpage>36</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 has become embedded in target identification, molecular representation, compound generation, virtual screening, preclinical prediction, and selected development workflows. Yet the significance of these applications remains difficult to judge because computational performance, experimental usefulness, translational value, and routine pharmaceutical readiness are frequently discussed as though they were equivalent outcomes. This critical review examines where artificial intelligence materially changes drug-discovery practice and where its contribution remains conditional, indirect, or unconfirmed. The review applies a stage-specific analytical approach that distinguishes data availability from data suitability, benchmark performance from prospective usefulness, molecular plausibility from developability, prediction from explanation or causality, and experimental confirmation from clinical translation. The evidence indicates that artificial intelligence has its most defensible value in bounded tasks involving large or structurally informative datasets, clearly specified objectives, rapid candidate prioritization, and experimental feedback. Examples include relational target analysis, focused molecular generation, structure-enabled screening, and the prioritization of compounds for assay testing. However, many reported gains remain partly attributable to dataset composition, automation, benchmark construction, chemical similarity, or evaluation choices rather than to a transferable algorithmic advantage. Evidence becomes progressively thinner when claims move from discovery-task acceleration to mechanistic validity, preclinical predictiveness, clinical benefit, regulatory acceptability, or improved portfolio success. The principal conceptual contribution of this review is a proposed value-and-limit interpretation in which claims are judged according to their application stage, validation setting, experimental confirmation, and permissible influence on pharmaceutical decisions. The synthesis is necessarily constrained by heterogeneous study designs, uneven reporting, selective publication of successful campaigns, and limited independent prospective evidence. Responsible adoption therefore requires evidence proportional to the consequence of the decision being supported rather than reliance on a generic designation of artificial-intelligence capability.</p>
      </abstract>
      <kwd-group>
                <kwd>Artificial intelligence</kwd>
                <kwd>Drug discovery</kwd>
                <kwd>Molecular design</kwd>
                <kwd>Target identification</kwd>
                <kwd>Virtual screening</kwd>
                <kwd>Translational validation</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>