Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Endocrine/metabolic disease

Diabetes

Endoplasmic reticulum to nucleus signaling 1 (ERN1; IRE1)

An SAR study identified small molecule modulators of IRE1 that could be useful for treating type 2 diabetes. IRE1 has both kinase and endonuclease activities that are overactive in type 2 diabetes. In vitro and in cell culture, one class of IRE1 modulators decreased the protein's kinase activity but increased its endonuclease activity compared with vehicle control. A second class of compounds inhibited both the kinase and endonuclease activity of IRE1. Next steps include testing compounds from the two classes in cell culture and mouse models of type 2 diabetes and dyslipidemia.
MannKind Corp. has compounds that inhibit IRE1 activity in preclinical development to treat multiple myeloma (MM).
Ruga Corp. has an inhibitor of IRE1 activity in preclinical development for the same indication.

SciBX 5(43); doi:10.1038/scibx.2012.1140
Published online Nov. 1, 2012

Patent pending; available for licensing

Wang, L. et al. Nat. Chem. Biol.; published online Oct. 21, 2012;
doi:10.1038/nchembio.1094
Contact: Dustin J. Maly, University of Washington, Seattle, Wash.
e-mail:
maly@chem.washington.edu

Contact: Feroz R. Papa, University of California, San Francisco, Calif.
e-mail:
frpapa@medicine.ucsf.edu