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Ref Type
PMID (27203384)
Authors Zhang J, Liu C, Shi W, Yang L, Zhang Q, Cui J, Fang Y, Li Y, Ren G, Yang S, Xiang R
Title The novel VEGF receptor 2 inhibitor YLL545 inhibits angiogenesis and growth in breast cancer.
Journal Oncotarget
Date 2016 May 17
Abstract Text 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.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
YLL545 YLL545 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
YLL545 VEGFR2 Inhibitor 35 YLL545 inhibits KDR (VEGFR2), resulting in decreased downstream signaling and potentially leading to decreased angiogenesis and reduced tumor cell proliferation and tumor growth (PMID: 27203384).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown triple-receptor negative breast cancer not applicable YLL545 Preclinical - Cell line xenograft Actionable In a preclinical study, YLL545 inhibited proliferation of a human triple-negative breast cancer (TNBC) cell line in culture, and inhibited activation of STAT3 and ERK and decreased tumor growth in TNBC cell line xenograft models (PMID: 27203384). 27203384