Identification of Novel Functional Inhibitors of Acid Sphingomyelinase Novel FIASMAs
2011

Identifying New Drugs that Inhibit Acid Sphingomyelinase

Sample size: 276 publication 10 minutes Evidence: high

Author Information

Author(s): Kornhuber Johannes, Muehlbacher Markus, Trapp Stefan, Pechmann Stefanie, Friedl Astrid, Reichel Martin, Mühle Christiane, Terfloth Lothar, Groemer Teja W., Spitzer Gudrun M., Liedl Klaus R., Gulbins Erich, Tripal Philipp

Primary Institution: Department of Psychiatry and Psychotherapy, University of Erlangen, Erlangen, Germany

Hypothesis

FIASMAs have shared structural and physicochemical properties allowing high lysosomal drug concentrations.

Conclusion

The study identified 27 novel functional inhibitors of acid sphingomyelinase (FIASMAs) that could be used to treat various diseases.

Supporting Evidence

  • FIASMAs were found to have distinct physicochemical properties.
  • Functional inhibition of ASM was associated with good permeability across the blood-brain barrier.
  • FIASMAs were identified among various therapeutic drug classes.

Takeaway

The researchers found new drugs that can help stop a harmful enzyme in the body, which could help treat diseases like Alzheimer's.

Methodology

The study used a combination of experimental testing and machine learning to identify and classify compounds based on their ability to inhibit acid sphingomyelinase.

Potential Biases

Selection bias may have influenced the bimodal distribution of functional inhibition.

Limitations

The model is valid only for small drug-like molecules and does not account for in vivo therapeutic conditions.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1371/journal.pone.0023852

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