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Compound\n                    <jats:bold>5f<\/jats:bold>\n                    ((\n                    <jats:italic>E<\/jats:italic>\n                    )\u2010\n                    <jats:italic>N<\/jats:italic>\n                    '\u2010(2,6\u2010dichlorobenzylidene)\u20102\u2010((5\u2010methyl\u20101,3,4\u2010thiadiazol\u20102\u2010yl)thio)acetohydrazide) emerged as the most potent SHP2 inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.120 \u00b1 0.006 \u00b5M). Further, cell\u2010based studies revealed its moderate yet best\u2010in\u2010library cytotoxicity against MCF\u20107 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 86.46 \u00b1 2.32 \u00b5M) in a dose\u2010dependent manner. Compound\n                    <jats:bold>5f<\/jats:bold>\n                    also exhibited in vitro anti\u2010survival (33% colony formation) and anti\u2010migratory effect (45% wound closure) on MCF\u20107 cells upon treatment with sub\u2010IC\n                    <jats:sub>50<\/jats:sub>\n                    dose. In vivo toxicological evaluation of compound\n                    <jats:bold>5f<\/jats:bold>\n                    revealed excellent safety profile in mice at an oral dose of 2000\u00a0mg\/kg BW. Our current study yielded a novel heterocyclic scaffold designed through systematic lead\u2010guided optimization displaying submicromolar SHP2 inhibitory activity. The lead molecule identified from in vitro studies was effective against the proliferation, survival and migration of human breast cancer cells with an excellent in vivo safety profile.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202402997","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T14:09:29Z","timestamp":1745330969000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design and Synthesis of\n                    <i>S<\/i>\n                    \u2010Acetophenylhydrazones of 5\u2010Methyl\u20101,3,4\u2010Thiadiazole\u20102\u2010Thiol as SHP2 Inhibitory Agents"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-8883","authenticated-orcid":false,"given":"Rangan","family":"Mitra","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry Research Laboratory II Department of Pharmaceutical Engineering and Technology Indian Institute of Technology (Banaras Hindu University)  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0826-6546","authenticated-orcid":false,"given":"Sandeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Research Laboratory II Department of Pharmaceutical Engineering and Technology Indian Institute of Technology (Banaras Hindu University)  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-6590","authenticated-orcid":false,"given":"Aiswarya","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Laboratory Department of Pharmaceutical Engineering and Technology Indian Institute of Technology (Banaras Hindu University)  Varanasi Uttar Pradesh 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