Cornell University

University of Connecticut

Tri-institutional Therapeutics Discovery Institute

Timothy Hla

Kevin Patrick Claffey

Ji-Hye Paik

Teresa Sanchez

Michael Andrew Foley

Yoshiyuki Fukase

Ayumu Sato

Victoria Blaho

Christina Christoffersen

Lars Bo Nielsen

Sylvain Galvani

Hideru Obinata

Irina Jilishitz

Hiroki Takahagi

Andrew Stamford

William J Polvino

Hideyuki Igawa

Asato Kina

Yasufimi Wada

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

Pyridinone- and pyridazinone-based compounds and uses thereof

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.

Endothelium protective materials and methods of use

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.

Methods of inhibiting vascular permeability and apoptosis

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.

Growing community of inventors

Avon, CT, United States of America

Timothy Hla