Summary of the technology
Novel ceramide analogs with effects on pure acid ceramidase activity. These novel compounds were found to inhibit both the degradation (“forward” reaction) and synthesis (“reverse” reaction) of BODIPY-conjugated and/or 14C-labeled C12 ceramide by this enzyme. In addition these these compounds were tested in in vivo models in mice. Notably, each compound was highly toxic to the cells, and induced apoptotic cell death as judged by Caspase 3 activation. Moreover, each compound led to an elevation of cellular ceramide via multiple effects on sphingolipid metabolism. At least three of these effects (inhibition of acid ceramidase activity, inhibition of sphingomyelin synthesis, and inhibition of glycosphingolipid synthesis) could lead to an elevation of cellular ceramide, explaining the potent pro-apoptotic activity and their potential use as anti cancer leads.
Project ID : 12-2006-594
Description of the technology
Results in mouse and human cell models validate approach
Ceramide, apoptosis, cancer, sphingolipids, prostate cancer
Considerable anticancer activity in vivo in prostate, colon, pancreas and melanoma mouse models of human tumors. In vitro activity in various human cancer cell lines.
Filed in US, Europe, Japan and Israel
Second provisional patent filed
Novel new compounds
Considerable anticancer activity observed with local or even in metastatic cancer of prostate, colon, pancreas and melanoma mice models. Analog were injected intradermally or intraperitoneally or given per os to mice bearing human tumors.
Provides powerful stand alone or adjunctive therapy with irradiation or chemotherapy for cancer
Elevates cellular ceramide, inducing cytotoxicity and death by apoptosis
Leverages proven treatment models
Synthetic compounds activates procaspase-3 and induce
Increase the caspase-3 activity six to seven fold
Treatment with an analog resulted in tumor regression in mice
Provides more efficacious cancer treatment
Attenuates treatment process, reducing patient discomfort
Addresses needs for expanding cancer market
Further in vivo mouse models
Pharmacokinetic pharmacodynamic experiments
In vivo human testing
VP, Business Development, Healthcare
HUJI, Faculty of Medicine
About Yissum - Research Development Company of the Hebrew University
Technology Transfer Office from IsraelYissum - Research Development Company of the Hebrew University
Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.