title: SKLB-287, a novel oral multikinase inhibitor of EGFR and VEGFR2, exhibits potent antitumor activity in LoVo colorectal tumor model.
abstract: Colorectal cancer (CRC) is the third common cancer and most of the chemotherapies of CRC currently used often suffer limited efficacy and large side effects. Targeted small-molecule by anti-tumor drugs are thought a promising strategy for improving the efficacy and reducing the side effects. In this investigation, we report a novel multikinase inhibitor, termed SKLB-287, which was discovered by us recently. SKLB-287 could efficiently inhibit the activation of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2). It displayed very good anti-proliferative activity against LoVo CRC cells and considerable antiangiogenic potency in transgenic zebrafish embryos. Oral administration of SKLB-287 resulted in dose-dependent suppression of tumor growth in LoVo xenograft mouse model. Immunohistochemistry was adopted to examine the in vivo anti-tumor mechanism of action of SKLB-287.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: H-W
authors.initials: HW
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: M-W
authors.initials: MW
authors.lastname: Zheng
authors.forename: L
authors.initials: L
authors.lastname: Zhong
authors.forename: X-Y
authors.initials: XY
authors.lastname: Fu
authors.forename: Y-L
authors.initials: YL
authors.lastname: Pan
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Chen
authors.forename: L-L
authors.initials: LL
authors.lastname: Li
authors.forename: S-Y
authors.initials: SY
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D047428:Protein Kinase Inhibitors; C000598095:SKLB-287; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2