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bioRxiv · 10.1101/2023.01.23.525154

A network pharmacology approach to assess the comparative pharmacodynamics of pharmaceutical excipient trehalose in human, mouse and rat

Friend, J.·Kumar, A. H.
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Abstract

BackgroundTrehalose is used as a pharmaceutical excipient due to its several desirable pharmacokinetic and historically evident safety features. However, information on the pharmacodynamic properties of trehalose is lacking. Hence this study evaluated the comparative pharmacodynamic properties of trehalose using a network pharmacology approach. Materials and methodsThe specific targets of trehalose in human, mouse and rat were identified from the SwissTargetPrediction database, categorised and compared. The expression profile and subcellular localisation of the targets of trehalose in human was identified and correlated with the affinity of trehalose to these targets to assess its impact on the pharmacodynamic properties of trehalose. The affinity of trehalose to its metabolising enzyme in human, mouse, and rat was assessed by molecular docking and compared. ResultsA significant difference in the target categories and target types of trehalose was observed in human, mouse, and rat. The affinity of trehalose to human (66.03 {+/-} 5.1 M), rat (102.53 {+/-} 11.3 M) and mouse (42.07 {+/-} 5.3 M) trehalase was significantly different. Family A G protein coupled receptors were identified as the major target category of trehalose and cyclin dependent kinase 1 was observed as the high affinity target of trehalose in human and mouse. The correlation of target expression and affinity indicated minimal pharmacodynamic influence under physiological conditions. ConclusionThis study reports the selective targets of trehalose relevant to drug discovery and development protocols and highlights the limitations of rodent models in translating pharmacodynamic analysis of trehalose for development of human therapeutics.

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Friend, J., Kumar, A. H.. 2023-01-23. A network pharmacology approach to assess the comparative pharmacodynamics of pharmaceutical excipient trehalose in human, mouse and rat. https://doi.org/10.1101/2023.01.23.525154

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