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
Validated approach in small animals and human cell models
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.
- 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 activate procaspase-3 and induceapoptosis
- Increases the caspase-3 activity six to seven fold
- Treatment with an analogue resulted in tumor regression in mice
- Higher efficiency for cancer treatment
- Attenuates treatment process, reducing patient discomfort
- Addresses needs for further expand to cancer market
- Further in vivo mouse models
- Pharmacokinetic pharmacodynamic experiments
- Progress to In vivo human testing