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The aim of this study was to identify new RON inhibitors using virtual screening methods. <jats:bold>Methods<\/jats:bold>: To this end, a ligand\u2010based virtual screening approach was employed for screening of ZINC database on the homology model of RON receptor. All the selected hits were inspected in terms of drug\u2010likeness, ADME properties, and toxicity profiles. Ligand\u2010based similarity searches along with further filtering criteria led to the identification of two compounds, TKI1 and TKI2 that were evaluated using <jats:italic>in\u2005vitro<\/jats:italic> cell\u2010based RON inhibition assays. <jats:bold>Results<\/jats:bold>: The results showed that TKI1 and TKI2 could reduce phosphorylation of RON. Both compounds showed inhibitory activity of the downstream mTOR pathway with no apparent effects on other signaling mediators in a dose\u2010dependent manner. <jats:bold>Conclusion<\/jats:bold>: These compounds can provide a basis for developing novel anti\u2010RON inhibitors applicable to cancer therapy using medicinal chemistry\u2010oriented optimization strategies.<\/jats:p>","DOI":"10.1002\/minf.202000181","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T10:26:27Z","timestamp":1607077587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ligand\u2010based Discovery of Novel Small Molecule Inhibitors of RON Receptor Tyrosine Kinase"],"prefix":"10.1002","volume":"41","author":[{"given":"Omid","family":"Zarei","sequence":"first","affiliation":[{"name":"Cellular and Molecular Research Center Research Institute for Health Development Kurdistan University of Medical Sciences  Sanandaj Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najme","family":"Faham","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City Utah"},{"name":"Department of Oncological Sciences University of Utah  Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hariprasad","family":"Vankayalapati","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City Utah"},{"name":"College of Pharmacy University of Utah  Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane L.","family":"Raeppel","sequence":"additional","affiliation":[{"name":"ChemRF Laboratories  3194, rue Claude-Jodoin Montr\u00e9al QC H1Y 3M2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana L.","family":"Welm","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City Utah"},{"name":"Department of Oncological Sciences University of Utah  Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Hamzeh\u2010Mivehroud","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center Tabriz University of Medical Sciences  Tabriz Iran"},{"name":"School of Pharmacy Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1195","volume":"8","author":"Ronsin C.","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06659.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119214"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704356"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706751"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3545"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai9338"},{"key":"e_1_2_7_9_1","volume":"1","author":"Brown N. 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