Edward Wells

Learn More
Using knowledge of the substrate specificity of cPLA(2) (phospholipases A(2)), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine "trap", and an acidic binding moiety. The resulting 1,3-diheteroatom-substituted(More)
OSI-7836 (4′-thio-β-d-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell death. This hypothesis has been examined by(More)
Regulatory recommendations for providing bioanalytical support for biological therapeutics have co-evolved with the increasing success of these unique pharmaceuticals. Immunoassays have been used to quantify biological macromolecules for more than 50 years. These assays rely on the use of antigen-specific antibodies. More recently, LC-MS methods have being(More)
Methods started in discovery are optimized as they progress through preclinical and clinical development. Making a robust assay includes testing individual steps for consistency and points of failure. Assays may be transferred, optimized and revalidated several times. A rugged assay will not only meet regulatory requirements, but will execute with a low(More)
Infection with human rhinovirus (HRV) is thought to result in acute respiratory exacerbations of chronic obstructive pulmonary disorder (COPD). Consequently, prevention of HRV infection may provide therapeutic benefit to these patients. As all major group HRV serotypes infect cells via an interaction between viral coat proteins and intercellular adhesion(More)
The prevailing image of youth gangs— with their symbols, colors, and territorial graffiti—is that they are found in the poorest neighborhoods of America’s large cities. Certainly, they are. In recent years, however, such gangs also have been popping up in outlying rural areas, far away from urban decay. A number of assumptions about these rural gangs are(More)
We report the design of novel, potent cPLA(2)α inhibitors that possess an α-methyl-2-ketothiazole that acts as a serine-reactive moiety. We describe the optimization of the series for potency and metabolic stability towards ketone reduction. This was achieved by attenuating the reactivity of the ketone using a combination of electronic and steric effects.
Pharmaceutical drug development is a complex and lengthy process, requiring excellent project and laboratory management skills. Bioanalysis anchors drug safety and efficacy with systemic and site of action exposures. Development of scientific talent and a willingness to innovate or adopt new technology is essential. Taking unnecessary risks, however, should(More)