Selective 12-Human Lipoxygenase Inhibitors for the Treatment of Diabetes and Clotting
Lead Inventor: David Maloney (NCATS)
Inventors: Theodore Holman (University of California, Santa Cruz), Jerry Nadler (Eastern Virginia Medical School), Michael Holinstat (Thomas Jefferson University), Anton Simeonov (NCATS), Ajit Jadhav (NCATS)
Ref. No.: E-134-2010/0
Abstract: This invention discloses small molecule inhibitors of human 12-lipoxygenase (12-hLO). 12-lipoxygenase expression, activation, and lipid metabolites have been implicated in type 1 and type 2 diabetes, cardiovascular disease, hypertension, Alzheimer's, and Parkinson's disease. The development of 12-hLO inhibitors may be a potent intracellular approach to decreasing the ability of platelets to form large clots in response to vessel injury or activation of the coagulation pathway.
Publications:
Protein Kinase C Regulation of 12-Lipoxygenase-Mediated Human Platelet Activation • Molecular Pharmacology •
March 2012 • Probe Development Branch, NCATS Chemical Genomics Center
Discovery of Potent and Selective Inhibitors of Human Platelet-Type 12-Lipoxygenase • Journal of Medicinal
Chemistry • Aug. 11, 2011 • Probe Development Branch, NCATS Chemical Genomics Center
12-Lipoxygenase: A Potential Target for Novel Anti-Platelet Therapeutics • Cardiovascular & Hematologic Agents in Medicinal Chemistry • July 1, 2011 • Probe Development Branch, NCATS Chemical Genomics Center
12-Lipoxygenase Products Reduce Insulin Secretion and β-Cell Viability in Human Islets • Journal of Endocrinology
and Metabolism • February 2010 • Probe Development Branch, NCATS Chemical Genomics Center
Resistance to Type 1 Diabetes Induction in 12-Lipoxygenase Knockout Mice • Journal of Clinical Investigation •
May 15, 1999 • Probe Development Branch, NCATS Chemical Genomics Center