The goal of assay development is to establish a robust experimental setup that can be used to obtain reproducible results. For this purpose, the experimental environmental variables must be adjusted in the best possible way. Thus, the assay provides stable, empirical data sets that act as a basis for sound, scientific evaluations and enable trustworthy recommendations for the subsequent steps in the drug development process. In our laboratory, every assay undergoes a thorough quality management process in which the data sets are evaluated and validated by the scientific committee of our screening team. Only when all assay variables meet our high evaluation standard is the assay approved for productive use in screening or SAR studies.
Using CRISPR technology as well as directed target overexpression, weare able to support you with design and creation of tailored cell models reflecting relevant disease processes. These allow for customized cell-based hit identification and deconvolution by HCA or reporter gene assays.
Our HCS team consists of scientists with longstanding expertise in microscopy techniques, automated image analysis and primary screening. They conduct our fully robotized high-content imaging platform and are able to perform large-scale phenotypic screening campaigns in optimal runtimes well known from standard primary approaches. We support you during labor-intensive SAR studies with a well-developed set of target-based mechanistic HCA assays. To answer your questions, we can use well-established 2D cell models as well as highly complex 3D tumor models. We analyze the spatially-cell-dependent substance effect at fixed predefined time points or in the dynamic system using multiparametric live-cell observations in microtiter plate format.
We can support you with identifying the physiologically relevant cell-based assay to answer your biological questions. Our experience allows us to select out of existing well-characterized cell-based endpoints and kinetic readout methodologies and to tailor the use of those to answer your biological questions. Customized solutions applying state of the art homogenous plate reader methodologies or generation of multiparametric data using by High Content microscopy or flow-cytometry is possible as well.
With our Protein Production Platform we provide tool proteins to enable assay development, HTS, protein structure determination and biophysical analysis. We have experience with a broad range of protein classes, including membrane proteins.
Our extensive Biophysics Platform comprises all state-of-the-art methods ranging from TSA, NanoDSF, SPR, NMR, MS, MST, ITC, DLS, CD-spectrometry* to characterize proteins, protein-SMOL interactions and protein-protein complexes. To support the lead finding and developing process we develop individual tailor made assays for:
*TSA – Thermal Shift Assay; NanoDSF – Nanoscale Differential Scanning Fluorimetry; SPR – Surface Plasmon Resonance; NMR – Nuclear Magnetic Resonance; MS – Mass Spectrometry; MST – Microscale Thermoporesis; ITC - Isothermal Titration Calorimetry; DLS – Dynamic Light Scattering; CD-Spectrometry – Circular Dichroism Spectrometry
Native Mass Spectrometry
Modern mass spectrometry is able to extract much more information from biological samples than just the molecular weight. While in conventional mass spectrometry all information of non-covalent interaction is lost, in native mass spectrometry protein-protein or protein-ligand interactions are retained in the gas phase. NUVISAN offers native mass spectrometry as an addition to our biophysics platform for analysis of protein complexes consisting of other proteins, SMOLs or co-factors to determine stoichiometries and binding affinities.
High-Throughput Mass Spectrometry
Beside classic light-based detection technologies for high-throughput screening of small molecule libraries, NUVISAN also offers a mass spectrometry-based automated, label-free, direct-detection approach: RapidFire-MS - an electrospray-based technology in 384‐well plate format which can cope with complex enzyme preparations and salt contaminations. For even higher throughput in 1536-well plate format state-of-the-art matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐ToF) MS can be used.
Targeted metabolomics allows the relative or absolute quantification of a predefined set of endogenous metabolites. NUVISAN offers targeted metabolite analysis of different matrices, as cell culture samples, plasma, and tissue samples. Targeted metabolomics provides, among others, information on cellular target engagement and the pharmacodynamics of cellular metabolite levels induced by drug treatments.
Mass Spectrometry based protein characterization
Beside classical technologies as eg. analytical SEC, nanoDSF and SLS we offer mass spectrometry to identify and characterize proteins. We analyze the homogeneity of protein preparations, investigate posttranslational modification of proteins, and can provide information on co-factor binding of proteins via native mass spectrometry.
Mass spectrometry to characterize covalent binders
Covalent binders have long been considered adventurous but have now regained widespread attention in drug discovery. Denaturing mass spectrometry by LC-ESI-MS or MALDI-MS turned out to be the gold standard to screen small covalent libraries or to study covalent binders by determine their kinact/KI values.
Mass spectrometry based proteomics
Proteomics enables the global and targeted analysis of proteins, including protein identification from purified proteins and complex protein samples, quantification based on label-free and isotope labeling (SILAC and TMT) techniques, detection and localization of posttranslational modifications (PTMs).
We offer high-throughput X-ray crystallography-based fragment screening services using our own diverse fragment library of ~950 fragments dissolved at 500mM DMSO. Screening of libraries from our clients is also an option. We have established a state-of-the-art platform from ‘crystal-2-fragment hit’ using different robots (Mosquito, Formulatrix Imager, Echo, Shifter) enabling short timelines for hit identification. Depending on the crystal system and throughput needed we use Synchrotron radiation and/or in -house X-ray capabilities (007HF X-ray source with Actor sample changer). In addition, we characterize the initial X-ray hits with a broad range of biophysical assays.
Link: Biophysics Platform
The primary screening campaign occupies a key position in the non-clinical drug discovery process. High-throughput screening (HTS) is used to identify molecules with suitable target-specific properties to develop a promising drug. In our fully automated laboratory, NUVISAN offers perfectly miniaturized, cost-effective assays for HTS campaigns. Our equipment enables both microplate-intensive screening of complex compound libraries on a large scale and focused screening of smaller sub-libraries consisting of well-selected, promising structural families. In addition to classical biochemical and cellular technologies for target-specific or phenotypic screening, our services also include fragment-based screening and NMR-based screening. The scientific question determines which screening technology is best suited to your project. We are prepared and well equipped to select the physiologically best screening technology for you.
During compound screening, primary hit lists are characterized by a large number of false positives. This is a desired effect that is consciously accepted. After all, one does not want to lose a potentially promising new structure. This makes it all the more important to use selected filtering methods and follow-up experiments to identify the compounds that actually show dose-dependent potency and efficacy at the target before investing further work in optimizing the structures found in the primary campaign. Advanced experimental approaches are combined with virtual chemical search algorithms to generate a well-developed hit list of compounds that show predictable competitive behavior in terms of expected dose-response dependence.
We combine high-throughput crystallography with biophysical methods to identify initial binders from a fragment library hand-selected by medicinal chemists. Subsequently, we apply fragment growing or linking approaches to structure determination to improve potency and selectivity. Our continuous access to high-brilliance synchrotron sources along with automated data collection allows fast and reliable retrieval of crystallographic data. Our inhouse established data analysis pipeline enables quick identification of datasets with high likelihood of fragment binding.
Please contact us for more information on our Fragment library and our Fragment2Lead Platform. One of our recent success stories can be found here:
NUVISAN has access to non-public data related to 3 million different structures comprising about 3 billion bioactivity and other compound measurements, contained in the Life Science Database. With this wealth of data, NUVISAN is in the position to generate proprietary machine learning and Artificial Intelligence (AI) models to support compound selection and optimization across a wide variety of endpoints. In addition, we can annotate chemical space with decision-relevant information not available with compound selected from other sources. Hence, the Life Science Database will make sure to use all available information to arrive at suitable bioactive chemical matter faster, and with less experimental cost.
we can annotate chemical space with decision-relevant information not available with compound selected from other sources.
When designing chemical libraries, NUVISAN‘s drug discovery scientists are able to draw on millions of electronically and physically available compound samples, which cover a wide range of chemical, physicochemical, and biological activity space. From this library, and with the help of the Life Science Database, we are able to annotate compounds with already existing information for better and more efficient compound selection, and to provide focused libraries to probe and modulate a wide range of biological processes. We provide both focused and diverse libraries selected according to a wide range of criteria, which can be utilized further in screening and other downstream steps in drug discovery programs.
NUVISAN is offering world-leading expertise and capabilities to develop the optimal assays for your target, run the screening campaign in ultra-high-throughput and follow up the hits in lead optimization until the clinical candidate compound is identified.
Our portfolio contains biochemical, biophysical as well as cell- and phenotypic-based HTS compatible assay technologies.
NUVISAN has over 20 years of experience in designing screening campaigns to reliably identify the most effective and selective compounds for your target. The flexible setup of our automated liquid handling and uHTS systems (>150,000 datapoints per day) allow us to run several screening campaigns in parallel and to adapt the workflows to your project needs.
NUVISAN can screen your compound library, but we have also access more than 3 million well-characterized compounds from Bayer's library to fuel your lead identification project's success. Our screening and medicinal chemists collaboratively evaluate the hit list to select the most promising candidates.
We possess several High-Content Screening setups based on poly-automated confocal Opera Phenix systems as well as brightfield microscopes to support 2d, 3d and 4d cellular assays and screening campaigns. Poly-automated cell cultivation and liquid handling stations enhance our throughput capabilities. Our powerful IT infrastructure supports multiparametric image analysis and artificial intelligence-based evaluation strategies.
NUVISAN supports hit-to-lead and lead optimization programs with a wide range of methods for compound characterization. Our very fast turnaround times of around one week from compound delivery to data report pave the way towards effective decision making based on comprehensive data sets in lead optimization cycles.
Moreover we have developed during the last 20 years profound knowledge in high-throughput binding kinetic characterization, mode of action studies, protein degradation assays, Schild analysis, selectivity assessment and orthologs assays.