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This study used targeted proteomics,\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    molecular docking, and simulation-based drug repurposing to identify potential drug candidates for HGGs. Importantly, we performed multiple reaction monitoring (MRM) on differentially expressed proteins with putative roles in the development and progression of HGGs based on our previous work and the published literature. Furthermore,\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    molecular docking-based drug repurposing was performed with a customized library of FDA-approved drugs to identify multitarget-directed ligands. The top drug candidates such as Pazopanib, Icotinib, Entrectinib, Regorafenib, and Cabozantinib were explored for their drug-likeness properties using the SwissADME. Pazopanib exhibited binding affinities with a maximum number of proteins and was considered for molecular dynamic simulations and cell toxicity assays. HGG cell lines showed enhanced cytotoxicity and cell proliferation inhibition with Pazopanib and Temozolomide combinatorial treatment compared to Temozolomide alone. To the best of our knowledge, this is the first study combining MRM with molecular docking and simulation-based drug repurposing to identify potential drug candidates for HGG. While the present study identified five multitarget-directed potential drug candidates, future clinical studies in larger cohorts are crucial to evaluate the efficacy of these molecular candidates. The research strategy and methodology used in the present study offer new avenues for innovation in drug discovery and development which may prove useful, particularly for cancers with low cure rates.\n                  <\/jats:p>","DOI":"10.1089\/omi.2023.0256","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T16:26:37Z","timestamp":1707236797000},"page":"59-75","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Multitarget Potential Drug Candidates for High-Grade Gliomas Identified by Multiple Reaction Monitoring Coupled with\n                    <i>In Silico<\/i>\n                    Drug Repurposing"],"prefix":"10.1177","volume":"28","author":[{"given":"Ayushi","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rushda","family":"Patel","sequence":"additional","affiliation":[{"name":"Sinhgad College of Pharmacy, Savitribai Phule Pune University, Pune, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atharva","family":"Mahale","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rujuta Vijay","family":"Thorat","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya Lipsa","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, National Institute of Technology, Warangal, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Epari","family":"Sridhar","sequence":"additional","affiliation":[{"name":"Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliasgar","family":"Moiyadi","sequence":"additional","affiliation":[{"name":"Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5159-6834","authenticated-orcid":false,"given":"Sanjeeva","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"e_1_3_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2019.101912"},{"key":"e_1_3_6_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122732"},{"key":"e_1_3_6_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2019.1599662"},{"key":"e_1_3_6_5_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2014.29.7.980"},{"key":"e_1_3_6_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.2c00646"},{"key":"e_1_3_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_3_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17458"},{"key":"e_1_3_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-016-0418-0"},{"key":"e_1_3_6_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1030"},{"key":"e_1_3_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094899"},{"key":"e_1_3_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11547-021-01381-5"},{"key":"e_1_3_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.10.004"},{"key":"e_1_3_6_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.4659"},{"key":"e_1_3_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2954"},{"key":"e_1_3_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01503-3"},{"key":"e_1_3_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800087"},{"key":"e_1_3_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0426-7"},{"key":"e_1_3_6_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.548243"},{"key":"e_1_3_6_20_1","first-page":"61833","article-title":"Quantitative proteomics workflow using multiple reaction monitoring based detection of proteins from human brain tissue","volume":"174","author":"Ghantasala S","year":"2021","unstructured":"Ghantasala S, , Pai MGJ, , Srivastava S. 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