更新于：2024-11-01

VEGFR1 x PDGFR x VEGFR2 x VEGFR3 x bFGF

更新于：2024-11-01

基本信息

关联

项与 VEGFR1 x PDGFR x VEGFR2 x VEGFR3 x bFGF 相关的药物

BMS-584622

靶点

PDGFR x VEGFR1 x VEGFR2 x VEGFR3 x bFGF

作用机制

PDGFR拮抗剂 [+4]

在研机构-

原研机构

Bristol Myers Squibb Co.

在研适应症-

非在研适应症

血管疾病

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 VEGFR1 x PDGFR x VEGFR2 x VEGFR3 x bFGF 相关的临床结果

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100 项与 VEGFR1 x PDGFR x VEGFR2 x VEGFR3 x bFGF 相关的转化医学

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0 项与 VEGFR1 x PDGFR x VEGFR2 x VEGFR3 x bFGF 相关的专利（医药）

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项与 VEGFR1 x PDGFR x VEGFR2 x VEGFR3 x bFGF 相关的文献（医药）

2012-02-01·Cancer1区 · 医学

Cell surface receptor expression patterns in osteosarcoma

1区 · 医学

Article

作者: Sheref E. Hassan ; Sajida Piperdi ; Mikhail Bekarev ; Mimi Y. Kim ; Juan Lin ; David S. Geller ; Richard Gorlick

AbstractBACKGROUND:Although the presence of numerous cell signaling receptors in osteosarcoma is known, their simultaneous characterization has not been performed to date. The current study sought to characterize and quantify the expression of cell surface receptors across a variety of osteosarcoma cell lines.METHODS:Standard (n = 4) and patient‐derived (n = 10) osteosarcoma cell lines were cultured and labeled with antibodies to epidermal growth factor receptor, human epidermal growth factor receptor (HER)‐2, HER‐3, HER‐4, insulin‐like growth factor 1 receptor (IGF‐1R), IGF‐2R, insulin receptor (IR), vascular endothelial growth factor receptor (VEGFR)‐1, VEGFR‐2, VEGFR‐3, c‐Met, fibroblast growth factor receptor (FGFR)‐2, FGFR‐3, and platelet‐derived growth factor receptor (PDGFR)‐β. Cell surface examination was performed using flow cytometry, and the geometric fluorescent mean for each receptor was calculated and compared against a positive control.RESULTS:Significant overexpression of IGF‐2R was shown in all cell lines, with an average geometric mean above the upper expression quartile. A variable expression pattern was seen for c‐Met, PDGFR‐β, IR, IGFR‐1, HER‐2, and VEGFR‐3 with expression values for the remaining receptors mainly in the lower quartile. An apparent association between the expression of IGF‐1R and HER‐2 and between the expression of PDGFR‐β and IR was demonstrated.CONCLUSION:IGF‐2R was consistently overexpressed on the cell surface across all tested osteosarcoma cell lines. Substantial, although variable, expression of c‐Met, HER‐2, IGF‐1R, VEGFR‐3, IR, and PDGFR‐β was demonstrated as well, suggesting that these receptors may contribute to osteosarcoma aggressiveness and biological heterogeneity and may serve as potential targets within a subset of tumors. Associated receptor expression may provide new insight into common regulatory factors or pathways. Targeting either common factors or targeting multiple specific receptors may have therapeutic relevance. Cancer 2012;. © 2011 American Cancer Society.

2006-09-01·Cancer Research1区 · 医学

AMG 706, an Oral, Multikinase Inhibitor that Selectively Targets Vascular Endothelial Growth Factor, Platelet-Derived Growth Factor, and Kit Receptors, Potently Inhibits Angiogenesis and Induces Regression in Tumor Xenografts

1区 · 医学

Article

作者: Neervannan, Sesha ; Cattley, Russell ; Radinsky, Robert ; Diaz, Zobedia ; Coxon, Angela ; Bready, James ; Alva, Gonzalo ; Tasker, Andrew ; Chen, Danlin ; Talvenheimo, Jane ; Patel, Vinod ; Starnes, Charlie ; Polverino, Anthony ; Gan, Yongmei ; Wang, Ling ; Kendall, Richard ; Kumar, Gondi ; Meyer, James ; Montestruque, Silvia ; Kaufman, Stephen ; Estrada, Juan ; DeMelfi, Thomas

AbstractThe growth of solid tumors is dependent on the continued stimulation of endothelial cell proliferation and migration resulting in angiogenesis. The angiogenic process is controlled by a variety of factors of which the vascular endothelial growth factor (VEGF) pathway and its receptors play a pivotal role. Small-molecule inhibitors of VEGF receptors (VEGFR) have been shown to inhibit angiogenesis and tumor growth in preclinical models and in clinical trials. A novel nicotinamide, AMG 706, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4, platelet-derived growth factor receptor, and Kit receptors in preclinical models. AMG 706 inhibited human endothelial cell proliferation induced by VEGF, but not by basic fibroblast growth factor in vitro, as well as vascular permeability induced by VEGF in mice. Oral administration of AMG 706 potently inhibited VEGF-induced angiogenesis in the rat corneal model and induced regression of established A431 xenografts. AMG 706 was well tolerated and had no significant effects on body weight or on the general health of the animals. Histologic analysis of tumor xenografts from AMG 706–treated animals revealed an increase in endothelial apoptosis and a reduction in blood vessel area that preceded an increase in tumor cell apoptosis. In summary, AMG 706 is an orally bioavailable, well-tolerated multikinase inhibitor that is presently under clinical investigation for the treatment of human malignancies. (Cancer Res 2006; 66(17): 8715-21)