A5102966370- Computational Drug Discovery Methods
- Spectroscopy and Quantum Chemical Studies
- Pharmacogenetics and Drug Metabolism
- Radiopharmaceutical Chemistry and Applications
- Machine Learning in Materials Science
- Crystallography and molecular interactions
- Atmospheric Ozone and Climate
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Drug-Induced Hepatotoxicity and Protection
- Synthesis and Biological Evaluation
- Organometallic Complex Synthesis and Catalysis
- Synthesis and Reactivity of Heterocycles
- Advanced Chemical Physics Studies
- Atmospheric chemistry and aerosols
- Cardiac electrophysiology and arrhythmias
- Synthetic Organic Chemistry Methods
- Lanthanide and Transition Metal Complexes
- Analytical Chemistry and Chromatography
- Multiple and Secondary Primary Cancers
- Atmospheric aerosols and clouds
- Chemical Thermodynamics and Molecular Structure
- Metabolomics and Mass Spectrometry Studies
- Free Radicals and Antioxidants
- Synthesis and Reactions of Organic Compounds
Sanofi (Germany)
2014-2024
Charité - Universitätsmedizin Berlin
2024
Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung
2015-2018
Arizona State University
2008
European Synchrotron Radiation Facility
2008
Technical University of Darmstadt
2002-2003
Leipzig University
1996-1999
Institute of Molecular Biotechnology
1997
University of Zurich
1996
Migräne Klinik Königstein
1993
Successful drug discovery projects require control and optimization of compound properties related to pharmacokinetics, pharmacodynamics, safety. While volume chemotype coverage public corporate ADME-Tox (absorption, distribution, excretion, metabolism, toxicity) databases are constantly growing, deep neural nets (DNN) emerged as transformative artificial intelligence technology analyze those challenging data. Relevant features automatically identified, while appropriate data can also be...
The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from Greenland NEEM core to reconstruct environmental alterations in source regions accompanying these changes. Separating transport effects, find strongly reduced terrestrial biogenic emissions glacial times reflecting net loss of vegetated...
Hepatic toxicity is a key concern for novel pharmaceutical drugs since it difficult to anticipate in preclinical models, and can originate from pharmacologically unrelated drug effects, such as pathway interference, metabolism, accumulation. Because liver still ranks among the top reasons attrition, reliable prediction of adverse hepatic effects substantial challenge discovery development. To this end, more effort needs be focused on development improved predictive in-vitro in-silico...
Abstract. We measured condensation particle (CP) concentrations and size distributions at the coastal Antarctic station Neumayer (70°39´ S, 8°15´ W) during two summer campaigns (from 20 January to 26 March 2012 1 February 30 April 2014) polar night between 12 August 27 September 2014 in diameter (Dp) range from 2.94 60.4 nm (2012) 6.26 212.9 (2014). During both we identified all 44 new formation (NPF) events. From 10 NPF events, growth rates could be determined around 0.90 ± 0.46 h−1 (mean...
N-Nitrosamines (NAs) are a class of reactive organic chemicals that humans may be exposed to from environmental sources, food but also impurities in pharmaceutical preparations. Some NAs were identified as DNA-reactive mutagens and many those have been classified probable human carcinogens. Beyond high-potency mutagenic carcinogens need strictly controlled, low potency considered for risk assessment well. NA nitrosylated products active ingredients (APIs) often arise production processes or...
One of the most appreciated capabilities computational toxicology is to support design pharmaceuticals with reduced toxicological hazard. To this end, we have strengthened our drug photosafety assessments by applying novel computer models for anticipation in vitro phototoxicity and human photosensitization. These are typically used pharmaceutical discovery projects as part compound toxicity optimization methods. ensure good data quality aiming at global applicability separately compiled...
In silico driven optimization of compound properties related to pharmacokinetics, pharmacodynamics, and safety is a key requirement in modern drug discovery. Nowadays, large harmonized datasets allow implement deep neural networks (DNNs) as framework for leveraging predictive models. Nevertheless, various available model architectures differ their global applicability performance lead projects, such stability over time interpretability the results. Here, we describe compare value established...
The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes comprehensive integrated Weight of Evidence (WoE) approach to determine the need for 2-year rat study. In present work, experts from different organizations have joined efforts standardize as much possible procedural framework integration evidence associated S1B(R1) WoE criteria. uses pragmatic consensus procedure hazard assessment facilitate transparent, consistent, and...
From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through combination classical medicinal chemistry library approaches. This resulted in highly active small molecules with nanomolar activity good overall vitro ADME profile. Furthermore, compounds exhibited unusually high off-target selectivity due to their rigid structure.
Current 3D-QSAR methods such as CoMFA or CoMSIA make use of classical force-field approaches for calculating molecular fields. Thus, they can not adequately account noncovalent interactions involving halogen atoms like bonds halogen-π interactions. These deficiencies in the underlying force fields result from lack treatment anisotropy electron density distribution those atoms, known "σ-hole", although recent developments have begun to take specific bonding into account. We now replaced field...
For fasiglifam (TAK875) and its metabolites the substance-specific mechanisms of liver toxicity were studied. Metabolism studies run to identify a putatively reactive acyl glucuronide metabolite. In vitro cytotoxicity caspase 3/7 activation assessed in primary human dog hepatocytes 2D 3D cell culture. Involvement glutathione (GSH) detoxication system mediating was determined by assessing potentiation GSH depleted system. addition, potential mitochondrial liabilities compounds whole-cell...
Abstract Evaluation and mitigation of the potential carcinogenic risks associated with nitrosamines in marketed pharmaceutical products are areas interest for companies health authorities alike. Significant progress has been made to establish acceptable intake (AI) levels N ‐nitrosamine drug substance‐related impurities (NDSRIs) using SAR, however some compounds require experimental data support derivation a recommended AI. Many angiotensin‐converting enzyme inhibitors, identified by suffix...
Folgende Komplexe des funfuertigen Tichnitiums wurden dargestellt und charakterisiert TcNCl2[P(C6H5)3]2 (A) Tc NCl2 (PR2C6H5)3 [R = CH3 (B) bzw. C2H5 (C)] TcN[(C2H5)2NCS2]2 (D) Die Darstellung von erfolgt anlog der entsprechenden Rheniumkomplexes; (B), (C) durch Reaktron mit uberschunssigem PR2C6H5 Na(C2H5)2NCS2 Substitutionsreaktionen orhalten. genannten sind bomerkenswert hydrolysebestandig. Here IR- 1H-NMR-Spektren warden diskutiert
Abstract Joint academic–industrial projects supporting drug discovery are frequently pursued to deploy and benchmark cutting-edge methodical developments from academia in a real-world industrial environment at different scales. The dimensionality of tasks ranges small molecule physicochemical property assessment over protein–ligand interaction up statistical analyses biological data. This way, method development usability both benefit insights gained ends, when predictiveness readiness novel...