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Obesity; neurology

Diacylglycerol lipase-a (DAGLA)

In vitro studies identified a selective inhibitor of DAGLA that could help treat obesity or neurodegenerative diseases. In silico modeling aided design of a tetrahydrolipstatin-based inhibitor of DAGLA that inhibited the enzyme with nanomolar potency and was selective over other serine hydrolases in vitro. In cultured human neuroblastoma cells, the inhibitor decreased DAGLA activity compared with vehicle. Ongoing studies include improving potency and selectivity of the inhibitor and showing safety and activity in animals.

SciBX 6(48); doi:10.1038/scibx.2013.1402
Published online Dec. 19, 2013

Findings unpatented; not yet available for licensing

Baggelaar, M.P. et al. Angew. Chem. Int. Ed.; published online Oct. 31, 2013;
Contact: Mario van der Stelt, Leiden University, Leiden, the Netherlands