A5075225663- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- Heat shock proteins research
- Drug-Induced Hepatotoxicity and Protection
- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
- Cannabis and Cannabinoid Research
- Biosimilars and Bioanalytical Methods
- Health and Medical Research Impacts
- Enzyme-mediated dye degradation
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Spaceflight effects on biology
- Machine Learning in Materials Science
- Transgenic Plants and Applications
- Hepatitis B Virus Studies
- Cancer-related Molecular Pathways
- Privacy-Preserving Technologies in Data
- Chemical Reaction Mechanisms
- Cryptography and Data Security
- Plant Reproductive Biology
- Enzyme Catalysis and Immobilization
- Blockchain Technology Applications and Security
- Amino Acid Enzymes and Metabolism
University of Vienna
2017-2023
St George's, University of London
2022
BOKU University
2013-2014
Residence time and more recently the association rate constant kon are increasingly acknowledged as important parameters for in vivo efficacy safety of drugs. However, their broader consideration drug development is limited by a lack knowledge how to optimize these parameters. In this study on set 176 heat shock protein 90 inhibitors, structure–kinetic relationships, X-ray crystallography, molecular dynamics simulations were combined retrieve concrete scheme rationally slow down on-rates. We...
Transporters expressed in the liver play a major role drug pharmacokinetics and are key component of physiological bile flow. Inhibition these transporters may lead to drug-drug interactions or even drug-induced injury. Therefore, predicting interaction profile small molecules with help medicinal chemists toxicologists prioritize compounds an early phase development process. Based on comprehensive analysis data available public domain, we developed set classification models which allow...
An in vitro/in silico method that determines the risk of human drug induced liver injury relation to oral doses and blood concentrations drugs was recently introduced. This utilizes information on maximal concentration (Cmax) for a specific dose test compound, which can be estimated using physiologically-based pharmacokinetic modelling, cytotoxicity cultured hepatocytes. In present study, we analyzed if addition an assay measures inhibition bile acid export carriers, like BSEP and/or MRP2,...
Abstract Background Triple-negative breast cancer (TNBC) is a subtype of with limited treatment options and poor clinical prognosis. Inhibitors transcriptional CDKs are currently under thorough investigation for application in the multiple types, including cancer. These studies have raised interest combining these inhibitors, CDK12/13 inhibitor THZ531, variety other anti-cancer agents. However, full scope potential synergistic interactions CDK inhibitors kinase has not been systematically...
The bile salt export pump (BSEP) actively transports conjugated monovalent acids from the hepatocytes into bile. This facilitates formation of micelles and promotes digestion absorption dietary fat. Inhibition BSEP leads to decreased flow accumulation cytotoxic salts in liver. A number compounds have been identified interact with BSEP, which results drug-induced cholestasis or liver injury. Therefore, silico approaches for flagging as potential inhibitors would be high value early stage drug...
Molecular pharming in plants offers exciting possibilities to address global access modern biologics. However, differences the N-glycosylation pathway including presence of β(1,2)-xylose and core α(1,3)-fucose can affect activity, potency immunogenicity plant-derived proteins. Successful glycoengineering approaches toward human-like structures with no changes plant phenotype, growth, or recombinant protein expression levels have been reported for Arabidopsis thaliana Nicotiana benthamiana....
Prior to the clinical phases of testing, safety, efficacy and pharmacokinetic profiles lead compounds are evaluated in animal studies. These tests primarily performed rodents, such as mouse rats. In order reduce number experiments, computational models that predict outcome these studies thus aid prioritization preclinical candidates heavily needed. However, although for human off-target interactions with decent quality available, they cannot easily be transferred rodents due lack respective...
Machine learning (ML) models require an extensive, user-driven selection of molecular descriptors in order to learn from chemical structures predict actives and inactives with a high reliability. In addition, privacy concerns often restrict the access sufficient data, leading narrow space. Therefore, we propose framework re-trainable that can be transferred one local instance another, further allow less extensive descriptor selection. The are shared via Jupyter Notebook, allowing evaluation...
Auxin-binding protein 1 (ABP1) is suggested to be an auxin receptor which plays important role in several processes green plants. Maize ABP1 was simulated with the natural indole-3-acetic acid (IAA) and synthetic analog naphthalen-1-acetic (NAA), elucidate of KDEL sequence helix at C-terminus. The weakens intermolecular interactions between monomers but stabilizes C-terminal helix. Conformational changes C-terminus occur within are influenced by binding ligands. This observation helps...