Fraunhofer Institute for Molecular Biology & Applied Ecology – Screening Port, Germany
We are now witnessing a resurgence in drug discovery the use of cell-based assays including phenotypic assays where the underlying target/s are unknown. Concomitantly, significant advances in these assays are also being made, for example using human induced pluripotent stem (iPS) cell-derived cells that better recapitulate normal human biology compared to transformed cell lines and non-human primary cells.
A typical small molecule drug discovery project aims to identify chemical starting points that modify the functions of genes, cells, or biochemical pathways ultimately leading to new therapeutics. Screening using miniaturised microtiter plate formats remains the most widely utilised methodology for identifying novel chemical starting points that are capable of modulating target function in a meaningful, biologically relevant manner. The initial steps in small molecule drug discovery include the selection of a target, development of an assay to monitor its activity, and its screening against a compound library. Subsequently, the Primary Hits are optimised using multiple criteria including structure activity relationships, selectivity, physicochemical properties and liability that could result in a Lead compound series and eventually a clinical Candidate molecule for evaluation in human subjects and this compound is expected to possess appropriate physico-chemical properties, in-vitro off target liabilities, in-vitro toxicity and in-vitro ADME and safety profiles in order to improve their probability of progressing in the drug discovery value chain.
This presentation will discuss the strategies that have been adopted by various translational drug discovery projects with a specific focus on small molecule therapeutics.
Dr Sheraz Gul is Head of Drug Discovery, Assay Development & Screening at the Fraunhofer Institute for Molecular Biology and Applied Ecology. He is responsible for the global management of drug discovery activities and has 23 yearsʼ experience in both academia (University of London) and industry (GlaxoSmithKline Pharmaceuticals). This has ranged from the detailed study of catalysis by biological catalysts (enzymes and catalytic antibodies) to the design and development of assays for High Throughput Screening for the major drug target classes. He is the co-author of numerous papers, chapters and the Enzyme Assays: Essential Data handbook and has been organising drug discovery since 2011 across the world (Brazil, Hamburg, Italy, Portugal, Saudi Arabia and U.S.A) and thus far has been involved in the training of over 350 scientists.
In addition, he has been appointed to the editorial boards of the European Pharmaceutical Review and International Drug Discovery, is the Scientific Editor of Drug Target Review, a scientific co-founder of Transcriptogen Ltd and is an advisor to a number of biotech companies.
Chemistry Department, Faculty of Science, South Valley University, Egypt
Carbon paste electrodes (CPEs) which consists of a mixture carbon (graphite) with organic liquid, was used as a working electrode for selective and sensitive determination of some pharmaceuticals and drugs. To enhance the sensitivity, the carbon paste electrode was modified using different additives such as fatty acids, nanostructure materials, and others were added to the paste. This specific area of applied analytical chemistry offers extraordinary wide employment of CPEs and MCPEs in pharmaceutical analysis. On using Voltammetric procedures, different compounds accumulated and adsorbed on the electrode surface and reduced or oxidized giving a peak current corresponds the concentration of investigated analyte.
The methods were applied to determine the drugs or pharmaceuticals in biological media or in pharmaceutical formulation, a detection limit of about 1 x 10 -10M was achieved in some cases.
Mahmoud Khodari Maeila Hamed is a Prof. of Analytical chemistry in South Valley University, Qena, Egypt. His education is B.SC. (general chemistry) at May 1980 Assiut University, Egypt, M.Sc. (Analytical chemistry) 1985, Assiut University and Ph.D at (Analytical Chemistry) 1990, ULB, Belgium- Assiut University, Egypt. His Publications are 54 in the field of analytical chemistry, drug analysis. He attended 21 conferences and meetings.
Faculty of Chemistry and Biochemistry, Ruhr University of Bochum, Germany
Biochemistry seeks to understand life at a molecular level by examining the relationship between the structure and function of biomolecules, such as proteins, nucleic acids, and lipids. To achieve this, we use a variety of techniques, particularly biomolecular NMR spectroscopy, in order to determine the three-dimensional structures and dynamics of biomolecules as well as how they interact with each other and other molecules in solution at near-physiological conditions.
Cancer cells are hallmarked by the ability to divide unrestrictedly, posing an often lethal threat to an organism. Thus, the development of selective small antagonistic ligands tailored to bind to crucial protein targets is paramount to be able to treat cancer effectively. In order to achieve this goal, the molecular mechanism of a potential therapeutic effect needs to be elucidated at atomic resolution.
Our research focuses in the main on medically-relevant proteins, specifically those involved in the development of cancerous tumours, in order to better understand the causes of the condition and propose more effective treatment strategies. Examples include oncogenic proteins, tumour suppressors as well as proteins involved in malignant melanoma, to name but a few. Other current areas of investigation also cover the structure, function, dynamics, and interaction of proteins associated with the transduction of physiological signals as well as bioenergetics.
In particular, we would like to understand structure-function-relationships of MDM2, p53, Ras as well as Rheb GTPases, and the melanoma inhibitory activity (MIA) proteins. Our additional research efforts in medicinal chemistry include an “SAR by NMR”-like approach in order to develop potential lead structures of small molecular antagonists for these medically-relevant proteins. This presentation will cover recent advances from our research endeavours.
Raphael Stoll is Professor of Biomolecular Spectroscopy in the Faculty of Chemistry and Biochemistry at the Ruhr University of Bochum, Germany. He studied Physiological Chemistry and Biochemistry at the Universities of Tübingen, Germany, and Oxford, UK, as a fellow of the „Studienstiftung” and DAAD. Supported by a fellowship from the FCI, he carried out his doctoral research at the Max Planck Institute for Biochemistry in Munich and received his PhD from the Technical University of Munich. After a stay as a research associate at The Scripps Research Institute, CA, USA funded by first a DAAD- and then an Emmy-Noether fellowship, he initially joined the Ruhr-University of Bochum as Junior professor. His research focuses in the main on structure-function-relationships of medically-relevant proteins, specifically those involved in the development of cancerous tumours, in order to better understand the causes of the condition and propose more effective treatment strategies.
1Inonu University, Pharmacy Faculty, Department of Pharmacology, Turkey
2Firat University, Veterinary Faculty, Department of Pathology, Turkey
Abstract: The apricot is an important nutritional fruit in regard to itʼs content of mineral and vitamins. It is well- known the benefical effects of the apricot on gastrointestinal, cardio-vascular, nervous and musculoskletal system. The aim of this study was to evaluate the hepato-protective effects of the dietary apricot in rats induced by ketamine toxicity in regard to biochemical, histopathological and immunohistochemical examinations.
Material and Methods: In this study; twenty eight, male, 12 week old, Sparaque Dawley rats were divided into 4 groups, 7 rats in each. Group I: control group. Group II: rats were injected intraperitoneally with ketamine (100 mg/kg/day) for two weeks. Group III: rats received 5% apricot containing diet for 15 days Group IV: rats received 5% apricot containing diet and intraperitoneally injected ketamine (100 mg/kg/day) for 15 days. Serum levels of AST, ALT, ALP, GGT, TB, ALB levels were measured. Histological Liver sections were subjected to H & E, immunohistochemical stain (Caspase 3) and followed by statistical analysis. In group II; liver enzymes and immunohistochemical caspase-3 positivity were significantly increased as compared to control. Furthermore, there was hepatocytic vacuoler degeneration, focal necrosis and sinusoidal hyperemia. These lesions were less severe in group IV, whereas caspase immunoreactivity were less significant in group IV.
Results: Overall, apricot containing diet has hepatoprotective effects on ketamine toxicity in rats.
I was born in Malatya province of Turkey in 1965. In 1987, Iʼve finished University of Firat, Faculty of Veterinary Medicine, and finished Ph.D University of Selcuk, Health Sciences Institute in 2007. From February 2009, Iʼve been working University of Inonu, Faculty of Pharmacy, Department of Pharmacology as Assistant Professor Dr.