Yissum - Research Development Company of the Hebrew University

Synthetic, Non-natural Ceramide Analogs as Apoptotic Agents in Prostate Cancer

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

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

Categories

Ceramide, apoptosis, cancer, sphingolipids, prostate cancer

Development Stage

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.

Patent Status

Filed in US, Europe, Japan and Israel

Second provisional patent filed

Market Size

$8B

Highlights

  • 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

Our Innovation

  • Synthetic compounds activates procaspase-3 and induce

    apoptosis

  • Increase the caspase-3 activity six to seven fold

  • Treatment with an analog resulted in tumor regression in mice

The Opportunity

  • Provides more efficacious cancer treatment

  • Attenuates treatment process, reducing patient discomfort

  • Addresses needs for expanding cancer market

Development Milestones

  • Further in vivo mouse models

  • Pharmacokinetic pharmacodynamic experiments

  • In vivo human testing

Project manager

Ariela Markel
VP, Business Development, Healthcare

Project researchers

Arie Dagan
HUJI, Faculty of Medicine
Biochemistry

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About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

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.

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