{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:23:26Z","timestamp":1792531406245,"version":"4.5.0"},"reference-count":15,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG2202"],"award-info":[{"award-number":["RTG2202"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG2740; Project number 447268119"],"award-info":[{"award-number":["RTG2740; Project number 447268119"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG2740; Project number 447268119"],"award-info":[{"award-number":["RTG2740; Project number 447268119"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:p>\n                    The rise of drug resistances in malaria necessitates the exploration of novel therapeutic strategies. Targeting epigenetic pathways could open new, promising treatment avenues. In this study, the focus is on the essential Bromodomain protein 1 (\n                    <jats:italic>Pf<\/jats:italic>\n                    BDP1) of the malaria pathogen\n                    <jats:italic>Plasmodium falciparum.<\/jats:italic>\n                    Utilizing the pan\u2010selective bromodomain inhibitor MPM6, a potent initial hit is identified and it is subsequently developed into a nanomolar binder. Through a combination of virtual docking, isothermal titration calorimetry, and X\u2010ray crystallography, the molecular interactions of the new inhibitors with the bromodomain (BRD) of the protein (\n                    <jats:italic>Pf<\/jats:italic>\n                    BDP1\u2010BRD) are elucidated. The findings include the first co\u2010crystallized inhibitors with the structures of\n                    <jats:italic>Pf<\/jats:italic>\n                    BRD1\u2010BRD as well as the bromodomain of the close homologous protein of\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    (\n                    <jats:italic>Pv<\/jats:italic>\n                    BDP1\u2010BRD). The structures provide new insights into their binding mechanisms. Further validation using conditional knockdown of\n                    <jats:italic>Pf<\/jats:italic>\n                    BDP1 in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    demonstrates parasite sensitivity to the inhibitor, underscoring its potential in a targeted therapeutic approach against malaria.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500024","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T06:55:31Z","timestamp":1742280931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Novel Inhibitor against the Bromodomain Protein 1 of the Malaria Pathogen\n                    <i>Plasmodium Falciparum<\/i>"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7594-3810","authenticated-orcid":false,"given":"Marius","family":"Amann","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische Wissenschaften Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Hermann\u2010Herder\u2010Str. 9 79104 Freiburg im Breisgau Germany"},{"name":"Institut f\u00fcr Biochemie Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Alberstrasse 21 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Warstat","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Organische Chemie und Biochemie Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Albertstrasse 21 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay Kristin","family":"Rechten","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut \u2010 Klinische Mikrobiologie, Immunologie und Hygiene Universit\u00e4tsklinikum Erlangen and Friedrich\u2010Alexander\u2010Universit\u00e4t (FAU) Erlangen\u2010N\u00fcrnberg  Wasserturmstr. 3\u20105 91054 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Theuer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Organische Chemie und Biochemie Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Albertstrasse 21 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Schustereder","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut \u2010 Klinische Mikrobiologie, Immunologie und Hygiene Universit\u00e4tsklinikum Erlangen and Friedrich\u2010Alexander\u2010Universit\u00e4t (FAU) Erlangen\u2010N\u00fcrnberg  Wasserturmstr. 3\u20105 91054 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Clavey","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Alberstrasse 21 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-3898","authenticated-orcid":false,"given":"Bernhard","family":"Breit","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Organische Chemie und Biochemie Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Albertstrasse 21 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-2893","authenticated-orcid":false,"given":"Oliver","family":"Einsle","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Alberstrasse 21 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2830-7130","authenticated-orcid":false,"given":"Martin","family":"H\u00fcgle","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische Wissenschaften Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Hermann\u2010Herder\u2010Str. 9 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1837-2756","authenticated-orcid":false,"given":"Michaela","family":"Petter","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut \u2010 Klinische Mikrobiologie, Immunologie und Hygiene Universit\u00e4tsklinikum Erlangen and Friedrich\u2010Alexander\u2010Universit\u00e4t (FAU) Erlangen\u2010N\u00fcrnberg  Wasserturmstr. 3\u20105 91054 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-189X","authenticated-orcid":false,"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische Wissenschaften Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Hermann\u2010Herder\u2010Str. 9 79104 Freiburg im Breisgau 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