Take a look at our scientific poster, ‘VEGFR-3 signature expression by histology to classify patient population for the selective VEGFR-3 inhibitor EVT801’, recently presented by our experts at AACR 2023.
Take a look at our scientific poster, ‘VEGFR-3 signature expression by histology to classify patient population for the selective VEGFR-3 inhibitor EVT801’, recently presented by our experts at AACR 2023.
Tags: Posters
Drug-drug interaction (DDI) studies are an important part of the regulatory drug development process. The US FDA, EMA and Japanese PMDA have issued guidance on the conduct of these DDI studies, however, a harmonised guidance is currently under review (ICH M12) and is expected to be adopted in April 2024. The risk of DDI can be assessed in vitro and data analysed using models of varying complexity. As identifying potential safety issues is the main purpose of these studies, many of the models have been developed to over-estimate the risk of DDI .This, however, needs to be balanced with the risk of false positives and the potential of unnecessary clinical DDI studies which are expensive and time consuming to perform. It is essential, therefore, to choose the most accurate model when analysing data from in vitro DDI studies.
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LC-MS/MS produces highly sensitive, specific and reproducible data, however, throughput can be a limitation and this can lead to a bottleneck in sample analysis from pharmacokinetic (PK) studies.
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The Echo® MS system, developed by Sciex, uses Acoustic Ejection Mass Spectrometry (AEMS). This chromatography-free technology generates sample droplets and introduces small reproducible volumes of 2.5nL (scalable to 25nL with multiple injections) to the mass spectrometer via an Open Port Interface with minimal carryover. It not only reduces sample requirements, it also facilitates dramatic increases in throughput with the potential to run 1 second cycle times. Despite these advantages, current potential limitations include reduced sensitivity compared to conventional LC-MS/MS and interference due to lack of separation.
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Chinook Therapeutics and Evotec joined forces for a patient-centric target identification supported by strong translational evidence to initiate drug discovery programs with a focus on tubular failed repair and cross-talk in the tubulointerstitial niche.
Tags: Kidney diseases, Posters, Proteomics, Metabolomics & Biomarkers
At Evotec we are committed to the development and usage of new technologies. With the objective to stay at the cutting edge of science and propose innovative solutions, several working groups have been created and are actively involved in various fields: photochemistry, electrochemistry, flow chemistry, biocatalysis... As part of this strategy, the working group “green chemistry” aims to design chemical products and processes that reduce or eliminate the use or generation of hazardous substances. We are always looking for safer, greener and cleaner methodologies to reduce the environmental impact of our activities and adopt the green chemistry principles1. Green chemistry applies across the life cycle of a chemical product, including its design, manufacture, use, and disposal. Moreover, we are also engaged in energy saving to decrease the global carbon footprint of the company. Sustainability and green chemistry are implemented while maintaining our level of excellence in drug discovery. To reach our objectives, we have identified four areas of improvements:
This poster is focused on two areas in continuous improvement at Evotec: solvent alternatives and energy saving. Some examples of reactions carried out in renewable solvents such as MeTHF2 and DMI3 are presented. Alternatives to DCM (potential ozone depletory and suspected carcinogenic solvent) usage for work-up and purification are also shown4.
The poster was presented by Kim Spielmann at the Journées de Chimie Organique held on 2-4 November 2022 at the École Polytechnique, Palaiseau, France.
1Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press: New York, 1998, 30, By permission of Oxford University Press
2 a) Coby J. Clarke, Wei-Chien Tu, Oliver Levers, Andreas Bröhl, and Jason P. Hallett Chemical Reviews 2018, 118, 747 b) Pace, V., Hoyos, P., Castoldi, L., Domínguez de María, P. and Alcántara, A.R. ChemSusChem 2012, 5, 1369 c) Andrew Jordan, Callum G. J. Hall, Lee R. Thorp, and Helen F. Sneddon Chemical Reviews 2022, 122, 6749
3 a) Aricò, F.; Tundo, P. Beilstein J. Org. Chem. 2016, 12, 2256 b) F. Aricò, A. S. Aldoshin, P. Tundo, ChemSusChem 2017, 10, 53 c) Russo F., Galiano F., Pedace F., Aricò F., and Figoli A. CS Sustainable Chem. Eng. 2020, 8, 1, 659
4 a) Peterson E.A., Dillon B., Raheem I., Richardson P., Richter D., Schmidte R. and Sneddon H.F. Green Chem., 2014,16, 4060 b) Taygerly J.P., Miller L.M., Yeec A. and Peterson E.A. Green Chem., 2012,14, 3020 c) MacMillan D.S., Murray J., Sneddon H.F., Jamiesona C. and Watson A.J.B. Green Chem., 2012,14, 3016
Tags: Medicinal Chemistry, Blog, Posters
As the CNS is a complex organ system, neurotoxicity can be difficult to assess and detect during preclinical development in animal models.
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Tags: Posters, Toxicology & Safety
During analysis of samples from HT-ADME screening, non-specific binding can cause challenges due to accumulation within the analytical system. This can result in poor peak shape, low sensitivity, increasing back pressure/pressure spikes, carryover or system clogging.
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Cardiotoxicity in response to pharmaceutical drugs, chemicals and environmental toxicants can develop as a result of changes in structural integrity of cardiac tissue or functional changes in cardiac electrophysiology. The development of new approach methodologies (NAMs) is important in predicting these cardiotoxic liabilities.
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Tags: Posters, Toxicology & Safety
The cytochrome P450 enzyme, CYP46A1, is predominantly expressed in the brain and plays a major role in cholesterol metabolism by converting cholesterol to 24-hydroxy cholesterol.
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