Stephen J Gardell
Affiliation: Wyeth Research
- Neutralization of plasminogen activator inhibitor I (PAI-1) by the synthetic antagonist PAI-749 via a dual mechanism of actionStephen J Gardell
Wyeth Research, N2274, 500 Arcola Road, Collegeville, PA 19426, USA
Mol Pharmacol 72:897-906. 2007..Second, binding of PAI-749 to PAI-1 renders PAI-1 vulnerable to plasmin-mediated proteolytic degradation...
- A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemiaMark J Evans
Department of Cardiovascular and Metabolic Diseases, Wyeth Research, 500 Arcola Rd, Collegeville, PA 19426, USA
Am J Physiol Gastrointest Liver Physiol 296:G543-52. 2009..These studies demonstrate a consistent ability of WAY-362450 to lower both serum TG and cholesterol levels and suggest that synthetic FXR agonists may have clinical utility in the treatment of mixed dyslipidemia...
- Selective Kv1.5 blockers: development of (R)-1-(methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone (KVI-020/WYE-160020) as a potential treatment for atrial arrhythmiaBenjamin E Blass
Chemical Sciences, Wyeth Research, Collegeville, Pennsylvania 19426, USA
J Med Chem 52:6531-4. 2009..KVI-020 (4g) successfully demonstrated antiarrhythmic efficacy in a canine arrhythmia model, and these findings support its utility as an antiarrhythmic agent...
- Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic triglyceride synthesisJay Wrobel
Chemical and Screening Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA
J Med Chem 51:7161-8. 2008..These results suggest indazoles such as 13 may have an improved profile for potential use as a therapeutic agent...
- LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouseElaine M Quinet
Department of Cardiovascular Metabolic Diseases and Nuclear Receptor Biology, Wyeth Research, Collegeville, PA, USA
J Lipid Res 50:2358-70. 2009..WAY-252623 displays a unique and favorable pharmacological profile suggesting synthetic LXR ligands with these characteristics may be suitable for evaluation in patients with atherosclerotic dyslipidemia...
- GAP-134 ([2S,4R]-1-[2-aminoacetyl]4-benzamidopyrrolidine-2-carboxylic acid) prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogsJames K Hennan
Cardiovascular and Metabolic Disease Research, Collegeville, Pennsylvania, USA
J Cardiovasc Pharmacol Ther 14:207-14. 2009..0% + 3.5% in controls to 7.9% + 1.5% and 7.1% + 0.8% (P < .05) at the 2 highest doses of GAP-134. GAP-134 is an effective antiarrhythmic agent with potential to reduce ischemia/reperfusion injury...
- The gap junction modifier, GAP-134 [(2S,4R)-1-(2-aminoacetyl)-4-benzamido-pyrrolidine-2-carboxylic acid], improves conduction and reduces atrial fibrillation/flutter in the canine sterile pericarditis modelEric I Rossman
Cardiovascular and Metabolic Disease, Wyeth Research, Collegeville, PA 19426, USA
J Pharmacol Exp Ther 329:1127-33. 2009..These findings, along with its oral bioavailability, underscore its potential antiarrhythmic efficacy...
- Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- miceHelen B Hartman
Cardiovascular and Metabolic Disease Research, Wyeth Research, Collegeville, PA 19426, USA
J Lipid Res 50:1090-100. 2009..These results suggest that activation of FXR protects against atherosclerosis in the mouse, and this protective effect correlates with repression of bile acid synthetic genes, with mechanistic differences between male and female mice...
- Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascadeJ Steven Jacobsen
Departments of Discovery Neuroscience and Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
Proc Natl Acad Sci U S A 105:8754-9. 2008....
- A presenilin-independent aspartyl protease prefers the gamma-42 site cleavageMing Tain Lai
Department of Biological Chemistry, Merck Research Laboratories, West Point, Pennsylvania, USA
J Neurochem 96:118-25. 2006..More importantly, the PSIG activity displays a distinct preference in mediating the 42-site cleavage over the 40-site cleavage, thereby generating Abeta42 as the predominant product...