Markus Muehlbacher

Learn More
The prediction of blood-brain barrier permeation is vitally important for the optimization of drugs targeting the central nervous system as well as for avoiding side effects of peripheral drugs. Following a previously proposed model on blood-brain barrier penetration, we calculated the cross-sectional area perpendicular to the amphiphilic axis. We obtained(More)
Acid sphingomyelinase (ASM) is an important lipid-metabolizing enzyme cleaving sphingomyelin to ceramide, mainly within lysosomes. Acid ceramidase (AC) further degrades ceramide to sphingosine which can then be phosphorylated to sphingosine-1-phosphate. Ceramide and its metabolite sphingosine-1-phosphate have been shown to antagonistically regulate(More)
BACKGROUND Although there are successful examples of the discovery of new PPARγ agonists, it has recently been of great interest to identify new PPARγ partial agonists that do not present the adverse side effects caused by PPARγ full agonists. Consequently, the goal of this work was to design, apply and validate a virtual screening workflow to identify(More)
Drug-induced phospholipidosis (PLD) is a lysosomal storage disorder characterized by the accumulation of phospholipids within the lysosome. This adverse drug effect can occur in various tissues and is suspected to impact cellular viability. Therefore, it is important to test chemical compounds for their potential to induce PLD during the drug design(More)
We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression,(More)
Sphingolipids are not only structural components of biological membranes, but also play an important role in cellular signalling and, thus, are involved in cell proliferation and differentiation but also stress and cell death. It is therefore of great clinical relevance to define inhibitors of the enzymes involved in sphingolipid metabolism. Here, we(More)
Quantitative structure-property relationships for predicting the water-octanol partition coefficient, logP(OW), are reported. The models are based on local properties calculated at the standard isodensity surface using semiempirical molecular orbital theory and use descriptors obtained as the areas of the surface found in each bin in a predefined binning(More)
Drug-induced phospholipidosis (DIPLD), characterized by the accumulation of phospholipids within lysosomes, is suspected to impair lysosomal function and considered an adverse side effect of the administered medication. The increasing use of polypharmacy and the resultant elevated risks of adverse drug reactions raise the need to explore the effects of drug(More)
  • 1