Related Experiment Video
Updated: May 29, 2026
09:09
Preparation of Human Tissues Embedded in Optimal Cutting Temperature Compound for Mass Spectrometry Analysis
Published on: April 27, 2021
Inhibitors of specific ceramide synthases
Susanne Schiffmann1, Daniela Hartmann, Sina Fuchs
1Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
Biochimie
|September 28, 2011
Summary
Researchers identified novel inhibitors targeting ceramide synthases (CerSs), crucial enzymes in ceramide production. These compounds, derived from Fingolimod, show potential for developing new cancer therapies by selectively blocking specific CerS enzymes.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Ceramide synthases (CerSs) are essential enzymes for synthesizing ceramides, bioactive lipids with diverse cellular roles.
- Different ceramide N-acyl side chains (C14:0-C26:0) mediate distinct cell signaling pathways.
- Selective CerS inhibition offers therapeutic potential, particularly in cancer treatment.
Purpose of the Study:
- To identify and characterize novel functional inhibitors of ceramide synthases.
- To evaluate the inhibitory effects of FTY720-derived compounds on specific CerS isoenzymes.
- To explore the structure-activity relationships and biological impact of these inhibitors.
Main Methods:
- In vitro ceramide synthase activity assays were employed to determine inhibitory effectiveness.
- Two human cell lines (HCT-116 and HeLa) with distinct ceramide profiles were used for testing.
- Structure-activity relationships were analyzed for the identified inhibitors.
Main Results:
- Four novel functional CerS inhibitors were identified from the FTY720 lead structure.
- ST1058 and ST1074 preferentially inhibited CerS2 and CerS4.
- ST1072 potently inhibited CerS4 and CerS6, while ST1060 predominantly inhibited CerS2.
Conclusions:
- The identified compounds demonstrate selective inhibition of specific CerS isoenzymes.
- These novel inhibitors hold promise for targeted therapeutic strategies, especially in oncology.
- Further investigation into structure-activity relationships can guide the development of more potent and selective CerS inhibitors.
More Related Videos
Related Concept Videos
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
01:52Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...