{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:11Z","timestamp":1786977491919,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:p>\n                    Accurate and reliable quantification of protein\u2013ligand energetics at the screening stage is often complicated by ligand aggregation, hydrophobicity\u2010driven artifacts, and the need for cosolvents. Here, differential scanning calorimetry (DSC) as a quantitative, label\u2010free screening method is evaluated using BCL\u20102 as a model oncogenic target. Nine inhibitors (i.e., venetoclax, navitoclax; and seven previously prioritized BCL\u20102 hit inhibitors by our research group) are profiled across solvent systems, including neat DMSO, 10% DMSO, and a ternary matrix (S3: 10% DMSO, 90% sulfobutylether\u2010\u03b2\u2010cyclodextrin (SBE\u2010\u03b2\u2010CD) in saline). DSC yielded thermal transition temperatures and thermodynamic parameters (\n                    <jats:italic>\u0394H<\/jats:italic>\n                    ,\n                    <jats:italic>\u0394G<\/jats:italic>\n                    ) that enabled ranking of binding strength. Solubility challenges are addressed by S3, which improved thermal signal quality. Comparisons with time\u2010resolved fluorescence energy transfer (TR\u2010FRET) analysis, in vitro assays, and MM\/GBSA binding free energy results confirmed DSC's accuracy in detecting binding energetics. Collectively, these results position DSC as a robust, material\u2010efficient tool for thermodynamic screening of BCL\u20102 ligands and other poorly soluble compounds, and as a practical complement to isothermal titration calorimetry when solubility or kinetic limitations prevail.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500744","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:57:15Z","timestamp":1772963835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Advancing Accurate Quantification of Protein\u2010Ligand Interactions: Differential Scanning Calorimetry as a Precision Screening Tool Using BCL\u20102 as a Model System"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-6410","authenticated-orcid":false,"given":"Bircan","family":"Dinc","sequence":"first","affiliation":[{"name":"School of Medicine Department of Biophysics Bahcesehir University  Istanbul 34734 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-5177","authenticated-orcid":false,"given":"Berna","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry Istanbul Technical University  Istanbul 34469 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-992X","authenticated-orcid":false,"given":"Thomas","family":"Mavromoustakos","sequence":"additional","affiliation":[{"name":"Department of Chemistry Capodistrian Athens University  Zographou Athens 15771 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0426-0905","authenticated-orcid":false,"given":"Serdar","family":"Durda\u011f\u0131","sequence":"additional","affiliation":[{"name":"School of Medicine Department of Biophysics Bahcesehir University  Istanbul 34734 T\u00fcrkiye"},{"name":"Molecular Therapy Lab Department of Pharmaceutical Chemistry School of Pharmacy Bahcesehir University  Istanbul 34353 T\u00fcrkiye"},{"name":"Lab for Innovative Drugs (Lab4IND) Computational Drug Design Center (H\u0130TMER) Bah\u00e7e\u015fehir University  Istanbul 34734 T\u00fcrkiye"},{"name":"Quantitative System Biology Lab Faculty of Medicine Biruni University  Istanbul 34015 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.07.024"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c01309"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2004.04.031"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2022.140830"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.321"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.09.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4103\/0975-7406.76463"},{"key":"e_1_2_9_9_1","first-page":"167","volume":"21","author":"Gill P.","year":"2010","journal-title":"J. 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