Abstract: The various examples presented herein are directed to compounds of the formula A-L1-Het1-L2-Cy1 or a pharmaceutical acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein: A is cycloalkyl, aryl, arylalkyl or heterocyclyl; Het1 is heterocyclyl containing at least two heteroatoms; Cy1 is a heterocyclyl; L1 is a bond, alkyl, alkenyl or alkynyl linker; L2 is an acyl or alkyl linker; and A and Cy1 are different. The compounds are useful in the treatment of fibrotic diseases, abnormal vascular leak and pathological angiogenesis.

Abstract: The various examples presented herein are directed to compounds of the formula A-L1-Het1-L2-Cy1 or a pharmaceutical acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein: A is cycloalkyl, aryl, arylalkyl or heterocyclyl; Het1 is heterocyclyl containing at least two heteroatoms; Cy1 is a heterocyclyl; L1 is a bond, alkyl, alkenyl or alkynyl linker; L2 is an acyl or alkyl linker; and A and Cy1 are different. The compounds are useful in the treatment of fibrotic diseases, abnormal vascular leak and pathological angiogenesis.

Abstract: Apolipoprotein M forms a complex with sphingosine-1-phosphate (S1P) and is the carrier of S1P in high density lipoprotein particles and mediates its endothelial protective effect. Increasing the concentration of the apoM/S1P complex by administering it, either alone or in HDL particles, can prevent or treat diseases caused by endothelial cell injury, including inflammatory diseases, sepsis, atherosclerosis and acute lung injury, ischemic heart disease, stroke, vital organ failure after ischemic stress.

Abstract: Agonists of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated forms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

Abstract: Agonists of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated forms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

Abstract: Apolipoprotein M forms a complex with sphingosine-1-phosphate (S1P) and is the carrier of S1P in high density lipoprotein particles and mediates its endothelial protective effect. Increasing the concentration of the apoM/S1P complex by administering it, either alone or in HDL particles, can prevent or treat diseases caused by endothelial cell injury, including inflammatory diseases, sepsis, atherosclerosis and acute lung injury, ischemic heart disease, stroke, vital organ failure after ischemic stress.

Abstract: Agonists of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated forms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

Abstract: Agonist of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated forms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

Abstract: Agonist of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated froms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

Abstract: Methods for the inhibition of angiogenesis are presented, comprising affecting the response of the EDG-1 receptor by the administration of pharmaceutically effective antagonists of EDG-1 signal transduction. This invention is based in part on the discovery that Akt protein kinase phosphorylation is required for endothelial cell chemotaxis mediated by the EDG-1 G protein-coupled receptor. This invention relates to the use of modifiers of EDG-1 signal transduction to treat disorders of undesired angiogenesis.