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Small molecule inhibitors of ceramidases
Essa M Saied1, Christoph Arenz
1Humboldt Universität zu Berlin, Institute for Chemistry, Berlin, Germany.
Abstract:
The equilibrium between the pro-apoptotic ceramide and pro-vital sphingosine-1-phosphate is considered to be decisive for cell death or survival. The different ceramidases thus play key roles in cell fate and might offer attractive targets for pharmacological intervention. Although until recently only moderately active inhibitors have been described, first in vivo experiments suggest activity against cancer cell survival and multi-drug resistance. Here, we provide a brief overview on the different ceramidases, and we will review the known inhibitors and current strategies for further inhibitor development.
Insights
Ceramidases regulate cell fate by balancing ceramide and sphingosine-1-phosphate levels. Inhibitors targeting ceramidases show promise against cancer cell survival and multi-drug resistance.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- The balance between pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate is critical for cell fate.
- Ceramidases are key enzymes regulating this balance and are potential therapeutic targets.
Purpose of the Study:
- To provide an overview of different ceramidases.
- To review known ceramidase inhibitors.
- To discuss current strategies for developing novel ceramidase inhibitors.
Main Methods:
- Literature review of ceramidases.
- Analysis of existing ceramidase inhibitors.
- Discussion of drug development strategies.
Main Results:
- Ceramidases play crucial roles in cell death and survival pathways.
- Early in vivo studies indicate potential of ceramidase inhibitors against cancer cell survival and multi-drug resistance.
- Limited availability of highly active inhibitors has been a challenge.
Conclusions:
- Ceramidases represent attractive targets for pharmacological intervention in diseases involving cell fate regulation.
- Further development of potent ceramidase inhibitors is warranted for therapeutic applications, particularly in oncology.
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