Thermo Fisher Scientific screening collection helps identify promising compound

Thermo Fisher Scientific’s Maybridge HitFinder screening compound collection has helped scientists at the University of Minnesota identify and characterise a small-molecule inhibitor that holds promise for the development of anti-inflammatory drugs.

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; FABP is part of the body’s inflammatory and metabolic response pathways.

The collection was an invaluable tool in helping the team identify several strong leads – compounds that hold the potential for blocking FABP. Ultimately, from this library they identified HTS01037, a pan-specific FABP inhibitor with broad anti-inflammatory properties. This study was recently published by Professor Bernlohr and his team.¹

‘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 organisation 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 organisation 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 utilise the HitFinder collection again due to the excellent results and data that it has delivered, while being highly economical and easy to use,’ Prof. Bernlohr said.

The Maybridge HitFinder collection is a premier offering of drug-like screening compounds that 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%. Additionally, they have been selected to be non-reactive, ensuring fewer false positives and higher quality results.

For more information about the Maybridge HitFinder, please visit www.maybridge.com.

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.