Abstract: Compositions for inhibiting lipoxygenase enzymes (e.g., human epithelial 12/15-lipoxygenase (12/15-LOX) are provided. Compositions according to certain embodiments include a first solvent, a second solvent and a lipoxygenase inhibitor. In certain instances, the lipoxygenase inhibitor is present in the composition (e.g., compositions formulated for intravenous administration) at a concentration of 30 mg/mL or greater. Methods for treating or preventing a lipoxygenase (e.g., human epithelial 12/15-lipoxygenase (12/15-LOX))-mediated disease or disorder are also provided.

Abstract: The present application provides oxazoles-containing compounds, or a pharmaceutically acceptable salt thereof, that are 12/15-LOX inhibitors. Pharmaceutical compositions and methods of using these compounds for treating various conditions wherein 12/15-LOX is implicated (such as stroke) are also provided.

Abstract: Compounds for inhibiting human platelet-type 12-(S)-lipoxygenase (12-LOX) are provided. Compounds according to certain embodiments modulate platelet activation and hemostasis. In some embodiments, compounds described herein modulate platelet activation mediated by immune receptor, Fc?RIIa. Methods for modulating platelet reactivity (e.g., following vascular insult or injury) with the compounds are also described. Methods for treating or preventing a platelet-type 12-(S)-lipoxygenase (12-LOX)-mediated disease are also provided. Compositions for practicing the subject methods are also described.

Abstract: Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells.

Abstract: Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells.

Abstract: Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells.

Abstract: Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells.

Abstract: Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells.

Abstract: Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells.

Abstract: Disclosed are inhibitors of human 12-lipoxygenase of Formula (I) or (II), wherein R1, R2, R3, and R4 are as defined herein, that are useful in treating or preventing a 12-lipoxygenase mediated disease or disorder, e.g., diabetes. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal.

Abstract: Compounds that are effective lipoxygenase inhibitors, and methods and pharmaceutical compositions for inhibiting lipoxygenases and for treatment of lipoxygenase-mediated conditions in humans and other subjects. The compounds, methods and pharmaceutical compositions utilize subersic terpenoids, jaspic terpenoids, igernellic terpenoids, hippospongic terpenoids, halicondric terpenoids, dictyodendric terpenoids, and/or heteronemic terpenoids, and synthetic derivatives or analogs thereof. Exemplary compounds include (−)-subersic acid, (+)-subersin, jaspaquinol, (−)-jaspic acid, igernellin, halisufate 7, and hipposulfate C and D, and derivatives thereof.

Abstract: Compounds that are effective lipoxygenase inhibitors, and methods and pharmaceutical compositions for inhibiting lipoxygenases and for treatment of lipoxygenase-mediated conditions in humans and other subjects. The compounds, methods and pharmaceutical compositions utilize subersic terpenoids, jaspic terpenoids, igernellic terpenoids, hippospongic terpenoids, halicondric terpenoids, dictyodendric terpenoids, and/or heteronemic terpenoids, and synthetic derivatives or analogs thereof. Exemplary compounds include (−)-subersic acid, (+)-subersin, jaspaquinol, (−)-jaspic acid, igernellin, halisufate 7, and hipposulfate C and D, and derivatives thereof.