<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD with MathML3 v1.3 20210610//EN" "JATS-archivearticle1-3-mathml3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"
  dtd-version="1.3" xml:lang="en" article-type="research-article">
  <?DTDIdentifier.IdentifierValue -//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN?>
  <?DTDIdentifier.IdentifierType public?>
  <?SourceDTD.DTDName JATS-journalpublishing1.dtd?>
  <?SourceDTD.Version 1.2?>
  <?ConverterInfo.XSLTName jats2jats3.xsl?>
  <?ConverterInfo.Version 1?>
  <?properties open_access?>
  <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-6930</article-id>
      <article-id pub-id-type="doi">10.51847/0J4U9dEvXj</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Potency Is Only One Objective in the Computational Design of Medicines with Viable Pharmaceutical Futures</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Weber</surname>
                <given-names>Klaus</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Novakova</surname>
                <given-names>Petra</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Zhang</surname>
                <given-names>Li</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Bauer</surname>
                <given-names>Stefan</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Multi-Objective Drug Design, Faculty of Pharmaceutical Sciences, University of Bonn, Bonn, Germany.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Pharmaceutical Future Assessment, Faculty of Pharmacy, University of South Bohemia, České Budějovice, Czech Republic.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Viable Medicine Design, Faculty of Pharmacy, Zhejiang University, Hangzhou, China.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Beyond-Potency Optimization, Faculty of Pharmacy, University of Freiburg, Freiburg, Germany.
          </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="klaus.weber@uni-bonn.de">klaus.weber@uni-bonn.de</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>127</fpage>
      <lpage>138</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>Computational molecular design increasingly enables the generation, ranking, and optimization of chemical structures against predicted biological and physicochemical properties. However, many design systems continue to privilege potency or a closely related target-activity score as the dominant measure of molecular quality. This emphasis creates a conceptual mismatch between optimization success and pharmaceutical viability because a highly potent structure may remain unsuitable owing to inadequate exposure, undesirable target interactions, safety liabilities, synthetic difficulty, formulation constraints, or weak alignment with the intended therapeutic context. This Original Multiobjective Design Theory Article develops a proposed account of medicine design in which computational optimization is directed toward viable pharmaceutical futures rather than isolated property maxima. The article conceptualizes candidate quality as a position within a multidimensional objective space comprising efficacy, selectivity, exposure, safety, and manufacturability, with each domain represented by imperfect evidence and subject to programme-specific constraints. It further distinguishes compensatory trade-offs from non-compensatory failures, proposes a viable pharmaceutical region within which Pareto reasoning becomes scientifically meaningful, and argues that preferences should change as evidence accumulates across discovery stages. The central contribution is therefore not a universal scoring formula but a theory for organizing objectives, constraints, uncertainty, and preference specification around pharmaceutical decisions. The proposed account remains conceptual: it does not establish validated thresholds, universally correct objective weights, prospective workflow superiority, clinical utility, regulatory acceptability, or deployment readiness. Its principal implication is that computational medicine design should be evaluated by the quality and transparency of the candidate sets and decisions it supports, rather than by potency improvement or aggregate benchmark performance alone.</p>
      </abstract>
      <kwd-group>
                <kwd>Multiobjective molecular design</kwd>
                <kwd>Pharmaceutical viability</kwd>
                <kwd>Potency optimization</kwd>
                <kwd>Pareto reasoning</kwd>
                <kwd>Drug developability</kwd>
                <kwd>Preference specification</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>