Angiogenesis inhibitors identified by cell-based high-throughput screening: Synthesis, structure–activity relationships and biological evaluation of 3-[(E)-styryl]benzamides that specifically inhibit endothelial cell proliferation

2012 ◽  
Vol 20 (4) ◽  
pp. 1442-1460 ◽  
Author(s):  
Kihito Hada ◽  
Atsushi Suda ◽  
Kohsuke Asoh ◽  
Takuo Tsukuda ◽  
Masami Hasegawa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Angiogenesis Inhibitors ◽  
Biological Evaluation ◽  
Endothelial Cell Proliferation ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals High-Throughput Screening Identifies Idarubicin as a Preferential Inhibitor of Smooth Muscle versus Endothelial Cell Proliferation

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89349 ◽  
Author(s):  
Shakti A. Goel ◽  
Lian-Wang Guo ◽  
Bowen Wang ◽  
Song Guo ◽  
Drew Roenneburg ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Endothelial Cell Proliferation

scholarly journals Endostatin: A Promising Drug for Antiangiogenic Therapy

1999 ◽  
Vol 14 (4) ◽  
pp. 263-267 ◽  
Author(s):  
L. Cirri ◽  
S. Donnini ◽  
L. Morbidelli ◽  
P. Chiarugi ◽  
M. Ziche ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Antiangiogenic Therapy ◽  
Specific Inhibitor ◽  
Angiogenesis Inhibitors ◽  
Endothelial Cell Proliferation ◽  
Platelet Factor ◽  
Collagen Xviii ◽  
And Migration

Angiogenesis, the formation of new blood vessels from existing capillaries, is critical for tumors to grow beyond a few in size. Tumor cells produce one or more angiogenic factors including fibroblast growth factor and vascular endothelial growth factor. Surprisingly, antiangiogenic factors or angiogenesis inhibitors have been isolated from tumors. Some angiogenesis inhibitors, such as angiostatin, are associated with tumors while others, such as platelet-factor 4 and interferon-alpha are not. Endostatin, a C-terminal product of collagen XVIII, is a specific inhibitor of endothelial cell proliferation, migration and angiogenesis. The mechanism by which endostatin inhibits endothelial cell proliferation and migration is unknown. Endostatin was originally expressed in a prokaryotic system and, late, in a yeast system, thanks to which it is possible to obtain a sufficient quantity of the protein in a soluble and refolded form to be used in preclincial and clinical trials.

Calreticulin and Calreticulin Fragments Are Endothelial Cell Inhibitors That Suppress Tumor Growth

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2461-2468 ◽  
Author(s):  
Sandra E. Pike ◽  
Lei Yao ◽  
Joyce Setsuda ◽  
Karen D. Jones ◽  
Barry Cherney ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Tumor Growth ◽  
Angiogenesis Inhibitors ◽  
Full Length ◽  
Endothelial Cell Proliferation ◽  
Proliferation In Vitro

Several angiogenesis inhibitors are fragments of larger proteins that are themselves not active as angiogenesis inhibitors. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In the present study, we examined whether the full-length calreticulin molecule shares the antiangiogenic and antitumor activities of vasostatin. Similar to vasostatin, calreticulin selectively inhibited endothelial cell proliferation in vitro, but not cells of other lineages, and suppressed angiogenesis in vivo. When inoculated into athymic mice, calreticulin inhibited Burkitt tumor growth comparably with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids inhibited endothelial cell proliferation in vitro and Burkitt tumor growth in vivo comparably with vasostatin. An internal calreticulin fragment encompassing amino acids 120-180 also inhibited endothelial cell proliferation in vitro and angiogenesis in vivo comparably with calreticulin and vasostatin. These results suggest that the antiangiogenic activities of vasostatin reside in a domain that is accessible from the full-length calreticulin molecule and localize to calreticulin N-terminal amino acids 120-180. Thus, calreticulin and calreticulin fragments are inhibitors of angiogenesis that directly target endothelial cells, inhibit angiogenesis, and suppress tumor growth. This information may be critical in designing targeted inhibitors of pathological angiogenesis that underlies cancer and other diseases.

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