title: The novel VEGF receptor 2 inhibitor YLL545 inhibits angiogenesis and growth in breast cancer.
abstract: Their antiangiogenic effects make vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors useful for cancer treatment. However, most of these drugs have unexpected adverse side effects. Here, we show that the novel VEGFR2 inhibitor YLL545 suppressed tumor angiogenesis and growth in triple-negative breast cancer without adverse effects. YLL545 treatment also markedly inhibited proliferation, migration, invasion, and tube formation by human umbilical vascular endothelial cells (HUVECs) in vitro. These effects of YLL545 were equal to or greater than those seen with sorafenib. In addition, YLL545 inhibited VEGF-induced phosphorylation of VEGFR2 and activation of downstream signaling regulators, such as phospho-STAT3 and phospho-ERK1/2, in HUVECs. Embryonic angiogenesis assays in zebrafish and Matrigel plug assays in mice demonstrated that YLL545 inhibits angiogenesis in vivo. YLL545 also inhibited proliferation and induced apoptosis in MDA-MB-231 breast cancer cells both in vitro and in vivo, and 50 mg/kg/d YLL545 inhibited human tumor xenograft growth by more than 50% in BALB/c nude mice. These observations suggest YLL545 is a potentially useful anticancer drug candidate.
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Shi
authors.affiliation: School of Food and Bioengineering, Xihua University, Sichuan, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Organ Transplantation, Tianjin First Center Hospital, Tianjin, China.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cui
authors.affiliation: Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, China.
authors.forename: Yangwu
authors.initials: Y
authors.lastname: Fang
authors.affiliation: School of Food and Bioengineering, Xihua University, Sichuan, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.affiliation: Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010671:Phenylurea Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D011720:Pyrazoles; C000625866:YLL545; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: VEGFR2 inhibitor; angiogenesis; breast cancer; tumor gowth