Efomycine M: an inhibitor of selectins?
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Animals↗
Biomedical subjects
Judith Günther
Publications and source records attributed to Judith Günther.
Classifying "kinase inhibitor-likeness" by using machine-learning methods.
By using an in-house data set of small-molecule structures, encoded by Ghose-Crippen parameters, several machine learning techniques were applied to distinguish between kinase inhibitors and other molecules with no reported activity on any protein kinase. All four approaches pursued--support-vector machines (SVM), artificial neural networks (ANN), k nearest neighbor classification with GA-optimized feature selection (GA/kNN), and recursive partitioning (RP)--proved capable of providing a reasonable discrimination. Nevertheless, substantial differences in performance among the methods were observed. For all techniques tested, the use of a consensus vote of the 13 different models derived improved the quality of the predictions in terms of accuracy, precision, recall, and F1 value. Support-vector machines, followed by the GA/kNN combination, outperformed the other techniques when comparing the average of individual models. By using the respective majority votes, the prediction of neural networks yielded the highest F1 value, followed by SVMs.
Algorithms↗
Design and synthesis of macrocyclic inhibitors of phosphatase cdc25B.
Based on molecular modeling studies, macrocyclic inhibitors of phosphatase cdc25B were synthetically derived from steroids. A preliminary SAR for this new template was elaborated. A series of compounds shows inhibition of cdc25B in the low micromolar range and good selectivity versus other phosphatases. The compounds did not show a significant antiproliferative effect in MaTu or HaCaT cells.
Cell Cycle Proteins↗
[Response to the letter of M. Schulz].
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Attitude to Health↗
Relibase: design and development of a database for comprehensive analysis of protein-ligand interactions.
Knowledge discovery from the exponentially growing body of structurally characterised protein-ligand complexes as a source of information in structure-based drug design is a major challenge in contemporary drug research. Given the need for powerful data retrieval, integration and analysis tools, Relibase was developed as a database system particularly designed to handle protein-ligand related problems and tasks. Here, we describe the design and functionality of the Relibase core database system. Features of Relibase include, e.g. the detailed analysis of superimposed ligand binding sites, ligand similarity and substructure searches, and 3D searches for protein-ligand and protein-protein interaction patterns. The broad range of functions provided in Relibase and its high level of data integration, along with its flexible and intuitive interface, makes Relibase an invaluable data mining tool which can significantly enhance the drug development process. An example, illustrating a 3D query for quarternary ligand nitrogen atoms interacting with aromatic ring systems in proteins, a pattern found in pharmaceutically relevant target proteins such as, e.g. acetylcholine-esterase, is discussed.
Animals↗
Utilising structural knowledge in drug design strategies: applications using Relibase.
The concept of structure-based drug design is based upon an in-depth understanding of the principles of molecular recognition. Despite our lack of a thorough comprehension of these principles, the wealth of protein structures available opens up unprecedented possibilities for new insights from the analysis of these data. Unravelling universal rules of molecular recognition is certainly one of the most appealing goals. But our knowledge is enhanced also when studying the specific determinants that characterise single targets or target families only, and the factors governing and discriminating their recognition properties.Here, we illustrate how the structure-based design process can benefit from the consequent incorporation of database query tools. We discuss representative examples to address issues such as protein flexibility, water molecules in binding pockets, and ligand specificity as some of the most critical aspects of drug design. All studies are carried out using our database system Relibase. We also show the application of Relibase in searching for preferred geometrical patterns between interacting molecular fragments.
Animals↗
[Evidence-based pharmacology in community and hospital pharmacies--a vision of the future?].
Pharmacists are academically trained drug and medication specialists. Also in the eyes of the law, pharmacists are more than just specialised sales people for medication. As laid out in the regulations governing pharmacies, pharmacists see patients and experts in the fields of medicine, dentistry and veterinary science to whom they have to offer advice. The pharmacist's advisory activities, though, must not interfere with an existing doctor-patient relationship. All pharmaceutical activities in community and hospital pharmacies should therefore be based--similar to the medical faculty--on an evidence-based practice in the sense of an evidence-based pharmacy adopting all principles of Evidence-based Medicine. The challenge for pharmacists and doctors should therefore be to work together to increasingly develop common strategies in order to achieve optimal treatment for the benefit of the patient. Especially in the treatment of chronically ill patients, synergistic effects could be reached through open exchange and a closer linkage between medical and pharmaceutical activities. Such closer contacts between the two disciplines could be made at interdisciplinary colloquia or special subject-specific round table discussions. Pharmaceutical Care (PhC), i.e. the optimisation of medicational therapy of chronically ill patients through accompanying intensive pharmaceutical advice is desirable from the patient's point of view and could take some load off medical practitioners. Any questions as to the use of medication, potential side-effects or undesirable interaction with other medications, but also regarding additional preventive measures can be posed to qualified personnel by the patient collecting his/her medication in the pharmacy. Also, as community pharmacists see themselves as active medication specialists and valuable qualified advisors to the patient with regard of self-medication, increased investment in internal communication between colleagues and external communication with patients is desirable. In the hospital setting, the pharmacy is to be regarded as the central medication information office and should participate in interdisciplinary working groups for the development of clinical guidelines and substitution possibilities. Furthermore, hospital pharmacy should be consulted on pharmaco-economic questions and on planning and conducting clinical studies.
Evidence-Based Medicine↗