Thermo Fisher Scientific Screening Collection Helps Scientists at University of Minnesota Identify Compound that Holds Promise in Anti-Inflammatory Medicine
Professor David Bernlohr, Distinguished McKnight University Professor and Head of the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota, and his team used the HitFinder collection in studies of fatty-acid-binding protein (FABP) inhibitors. The collection was an invaluable tool in helping the team identify several strong leads – compounds that hold the potential for blocking FABP – which is part of the body’s inflammatory and metabolic response pathways. Ultimately, from this library they identified HTS01037, a pan-specific FABP inhibitor with broad anti-inflammatory properties. This study was recently published by Prof. Bernlohr and his team1.
“Molecular disruption of the lipid carrier AFABP/ap2 in mice has been found to result in improved insulin sensitivity, protection from atherosclerosis, as well as reduction in LPS-stimulated inflammation,” explained Prof. Bernlohr. “We were therefore interested in investigating the efficacy of small-molecule inhibitors in defining the mechanisms of AFABP/aP2 action that could ultimately deliver a pharmacologically beneficial compound. To achieve this we required a good quality chemical screening library as an essential starting point.”
Before beginning this research, Prof. Bernlohr evaluated several available screening libraries and selected the Maybridge HitFinder™ collection because of its ease of use, broad chemical coverage, high chemical and structural diversity, as well as simplicity of format and organization in 384 well formats.
“Upon using the HitFinder collection to deliver HTS01037, we also were very pleased with the reproducibility of the collection, the ability to rapidly evaluate a variety of chemical space and the organization and handling of the samples,” Prof. Bernlohr said.
From this initial study, the Bernlohr group has been able to expand its analysis of FABP inhibitors and use them to probe FABP function in a variety of cells and systems. “If we had to start over from scratch, I am confident that we would follow the same path and utilize the HitFinder™ collection again due to the excellent results and data that it has delivered, whilst being highly economical and easy to use,” Prof. Bernlohr said.
The Maybridge HitFinder collection is a premier offering of drug-like screening compounds which maintains the superior structural diversity of the Maybridge Screening Collection by using an industry standard clustering algorithm to select a statistically representative sample of the full collection. All compounds fit Lipinski guidelines for "drug-likeness" and have purity greater than 90 percent. Additionally, they have been selected to be non-reactive, ensuring fewer false positives and higher quality results.
Reference 1. Hertzel, A.V., Hellberg, K., Reynolds, J.M., Kruse, A.C., Juhlmann, B.E., Smith, A.J., Sanders, M.A., Ohlendorf, D.H., Suttles, J., Bernlohr, D.A. (2009) Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Protein. J Med Chem 52:6024–6031. PMC2755644.
For more information about the Maybridge HitFinder™, please visit www.maybridge.com.
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About Professor David Bernlohr
David Bernlohr, PhD is Distinguished McKnight University Professor and Head of the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota. He holds the Cargill Chair in Systems Biology of Human Metabolism and is expert in lipid metabolism with an emphasis on obesity and adipose metabolism. His laboratory utilizes a combination of biophysical, biochemical and molecular genetic approaches towards the study of fatty acid binding proteins, transporters and receptors functioning in adipocytes and macrophages. Dr. Bernlohr received his PhD from the University of Illinois-Urbana Champaign and carried out postdoctoral work at The Johns Hopkins School of Medicine. Visit www.cbs.umn.edu/BMBB/faculty/Bernlohr.D.A.shtml.