{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T21:26:06Z","timestamp":1776115566060,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CRG\/2023\/001580"],"award-info":[{"award-number":["CRG\/2023\/001580"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["IIRPSG\u20102024\u201001\u201001573"],"award-info":[{"award-number":["IIRPSG\u20102024\u201001\u201001573"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SR\/PURSE\/2023\/220"],"award-info":[{"award-number":["SR\/PURSE\/2023\/220"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    BRAF is one of the most commonly mutated oncogenes in human cancers. More than 90% of BRAF mutations are associated with malignant melanoma. Given the pivotal role of BRAF\n                    <jats:sup>V600E\/WT<\/jats:sup>\n                    mutations in melanoma progression and therapy resistance, our study focused on the design of phenyl\u2010substituted pyrimidin\u2010benzenesulfonamide hybrids in the [\u03b1C\u2010OUT\/DFG\u2010IN] conformation, inspired by previously synthesized molecules structurally related to FDA\u2010approved BRAF inhibitors. A total of ten derivatives were synthesized, and their ADME\u2010T properties, in silico binding affinities, in\u00a0vitro cytotoxic activities against a melanoma cell line and BRAF\n                    <jats:sup>V600E\/WT<\/jats:sup>\n                    kinase assay were thoroughly evaluated. All compounds exhibit selective and stronger affinity for the BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    mutant over the wild\u2010type BRAF protein and also adhere to Lipinski's Rule of Five. Overall, both computational and biological evaluations support that the synthesized compounds, particularly\n                    <jats:bold>VA03<\/jats:bold>\n                    , exhibit greater potency and selectivity toward the BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    mutant protein. Furthermore, the presence of electron\u2010withdrawing groups at the R\n                    <jats:sub>1<\/jats:sub>\n                    position appears to significantly enhance the cytotoxic activity of these derivatives.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70179","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T04:56:05Z","timestamp":1759812965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design, Synthesis, Molecular Docking,\n                    <scp>ADME<\/scp>\n                    \u2010T and In\u00a0Vitro Anticancer Assessment of Phenyl\u2010Substituted\u2010Pyrimidin\u2010Benzenesulfonamide Derivatives as Potential\n                    <scp>\n                      BRAF\n                      <sup>V600E<\/sup>\n                    <\/scp>\n                    <sup>\n                      \/\n                      <scp>WT<\/scp>\n                    <\/sup>\n                    Inhibitors"],"prefix":"10.1111","volume":"106","author":[{"given":"Ankit Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda Punjab India"},{"name":"Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences Sam Higginbottom University of Agriculture, Technology and Sciences  Prayagraj Uttar Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vineet","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vimlendu Kumar","family":"Sah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adarsh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amandeep Singh","family":"Kalsi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prateek","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, Quality Assurance and Pharmaceutical Chemistry, School of Pharmacy GITAM (Deemed to Be University)  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habibullah","family":"Khalilullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy Qassim University  Buraydah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6653-7335","authenticated-orcid":false,"given":"Amita","family":"Verma","sequence":"additional","affiliation":[{"name":"Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences Sam Higginbottom University of Agriculture, Technology and Sciences  Prayagraj Uttar Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/LCTT.S493835"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.08.042"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.farmac.2005.01.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107848"},{"issue":"1","key":"e_1_2_10_7_1","first-page":"49","article-title":"In\u2010Silico Docking Analysis of Phytochemicals From Mimosa pudica l Leaves as an Antiviral Agent Against Herpes Simplex Virus Type I","volume":"1","author":"Gopal S. 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