Acid ceramidase (AC) catalyzes the hydrolysis of the lipid messenger ceramide thereby regulating ceramide levels in cells. AC is involved in multiple physiological and pathological processes, including cancer resistance and neuropathic pain. Previous AC inhibitors are ceramide analogs with weak inhibitory activity in vitro and virtually no utility in vivo.
The present portfolio of inventions provides two chemically distinct classes of small-molecule inhibitors of intracellular AC activity, which act at single digit nanomolar concentrations in vitro and at low doses in vivo.
We are currently looking for commercial partners to further develop these AC inhibitors for treatment of cancers and other disorders in which modulation of the levels of ceramide is clinically relevant.
|United States Of America||Issued Patent||9,428,465||08/30/2016||2011-765|
|United States Of America||Issued Patent||0001411588||10/30/2014||2011-765|
Discovery of a New Class of Highly Potent Inhibitors of Acid Ceramidase: Synthesis and Structure–Activity Relationship (SAR). J. Med. Chem., 2013, 56(9):3518-3530 PubmedID: 23614460
Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity. Sci Rep. 2013; 3: 1035. PubmedID: 23301156
Benzoxazolone Carboxamides: Potent and Systemically Active Inhibitors of Intracellular Acid Ceramidase. Angew Chem 2014 Nov 13. doi: 10.1002/anie.201409042.
Oncology, Cancer, Pain, Acid Ceramidase