title: The sphingosine-1-phosphate derivative NHOBTD inhibits angiogenesis both in vitro and in vivo.
abstract: Sphingosine-1-phosphate (S1P) plays an important role in angiogenesis by stimulating DNA synthesis, chemotactic motility, and early blood vessel formation. Accordingly, the S1P signaling pathway is an attractive target for novel anti-angiogenic therapeutics. Here, we describe a small synthetic derivative of S1P that acts as an anti-angiogenic agent. We found that the S1P derivative NHOBTD [N-((2S,3R)-3-hydroxy-1-morpholino-4-(3-octylphenyl)butan-2-yl)tetradecanamide] suppressed S1P-induced invasion and tube formation by human umbilical vein endothelial cells. NHOBTD also suppressed S1P signaling, as seen by destabilization of hypoxia inducible factor-1 alpha (HIF-1α) and secretion of VEGF, a transcriptional target of HIF-1α. Moreover, NHOBTD profoundly blocked endogenous neovascularization of the chick embryo chorioallantoic membrane, without rupturing any existing vessels. Together, these results demonstrate that NHOBTD is a new anti-angiogenic molecule that is capable of perturbing S1P signaling, and provides the basis for developing new anti-angiogenic drugs.
authors: Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Beom Seok
authors: BS
authors: Kim
authors: Hyomi
authors: H
authors: Park
authors: Seung Hwan
authors: SH
authors: Ko
authors: Won Koo
authors: WK
authors: Lee
authors: Ho Jeong
authors: HJ
authors: Kwon
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008246:Lysophospholipids / Q000737:chemistry*; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology*; D009226:Myristates / Q000737:chemistry* / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008246:Lysophospholipids; D009025:Morpholines; D009226:Myristates; C568330:N-(3-hydroxy-1-morpholino-4-(3-octylphenyl)butan-2-yl)tetradecanamide; D042461:Vascular Endothelial Growth Factor A; C060506:sphingosine 1-phosphate; D013110:Sphingosine