This week in therapeutics

Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Endocrine/metabolic disease

Diabetes

Carboxylesterase 1
(CES1; hCE1)

In vitro and mouse studies suggest inhibiting CES1 could help treat type 2 diabetes. In mouse adipocytes, phenotypic screening for compounds that increased lipid storage coupled with activity-based protein profiling to indicate enzymatic targets blocked by the hits identified Ces3, the mouse ortholog of CES1, as the molecular target of bioactive compounds. In mouse models of diabetes, a Ces3 inhibitor protected animals from weight gain, decreased liver lipid accumulation and increased insulin sensitivity compared with vehicle. In adipose tissue from patients with type 2 diabetes, CES1 activity was upregulated compared with that in lean controls. Next steps could include developing inhibitors of the human target.

SciBX 7(4); doi:10.1038/scibx.2014.116
Published online Jan. 30, 2014

Patent and licensing status unavailable

Dominguez, E. et al. Nat. Chem. Biol.; published online Dec. 22, 2013;
doi:10.1038/nchembio.1429
Contact: Enrique Saez, The Scripps Research Institute, La Jolla, Calif.
e-mail:

esaez@scripps.edu
Contact: Benjamin F. Cravatt, same affiliation as above
e-mail:

cravatt@scripps.edu