We aid your search for new chemical matter for challenging targets. This endeavour will be achieved with insight from our rich life science database and extensive in-house expertise, together with our Digital Life Science team. Our long translational experience spans from target to clinical molecules.
BEST-IN-CLASS LIFE SCIENCE CHEMISTRY CAPABILITIES
Efficient design and synthesis of high-quality test compounds and chemical probes.
Close interaction with lead discovery in screening hit-list evaluation and long-standing expertise in the Hit-2-Lead process (hit selection, assessment and modification).
Rapid development of different clusters into viable lead structures to fit your lead structure profile.
Strong drug-hunting attitude within the Lead-2-Candidate process, short cycle-times in multi-dimensional lead optimization programs.
OPTIMIZATION OF MOLECULAR PROPERTIES IS A TEAM EFFORT
Close collaboration with computational compound design, therapeutic research functions (in vitro-, ex-vivo, in vivo studies for your target/ indication of interest) and preclinical compound profiling (DMPK property optimization) to identify a preclinical candidate according to an agreed target product profile.Application of state-of-the-art methodologies (photochemistry, electrochemistry, final stage diversification) to quickly synthesize the target compounds of interest.First-rate expertise in new modalities (e.g. PROTACs, ADCs) and modalities beyond small molecules (e.g. peptides).#
UPSCALING & ROUTE SCOUTING
We synthesize your API or intermediate on a large scale (up to 500g).
Route scouting and synthesis route optimization for your API or intermediates.
Special technology capabilities include e.g. high-pressure reactions, photochemistry, hydrogenation, carbonylation, flow chemistry.
In our Separation Technology Labs (STL) we can perform fast automated as well as customized purification of drug candidates and intermediates, using a variety of different methodologies such as SFC or MS-guided automated preparative HPLC.
Separation of stereoisomers on analytical or preparative scale can also be provided.
We offer the whole range of efficient and flexible small sample single applications and/or batch-wise purifications of test compounds and intermediates.
NUVISAN can help you to de-risk projects by getting detailed insights into the Mode of Action of your candidate molecules by ensuring on-target activity. We identify target engagement / pharmacodynamic biomarkers based on well-defined studies of the target biology using literature searches as well as bioinformatic analyses.
WE CAN SUPPORT YOU WITH FURTHER OPTIMIZATION OF YOUR LEAD SERIES BY EXAMINING THE EFFICACY IN IN VIVO ANIMAL MODELS
Further refinement of each early lead series, with respect to potency, selectivity, and PK properties, enables investigation of their efficacy in in vivo animal models.
We have long-standing experience with small molecules and biologics (Antibodies, ADCs).
We systematically assess the mechanism of action (MoA) of your compound on its target. Using in silico tools, big data mining, database screening, extraction and assembly, we identify pathway-disease-relations and entity recognitions; we scrutinize your target and its signalling pathways, and the Mode of Action of your compound. We help you to identify pathomechanisms which offer therapeutic rationales with optimum fit to your compound.
YOUR LEAD SERIES WILL BE FURTHER OPTIMIZED TO EXAMINE THE EFFICACY IN IN VIVO ANIMAL MODELS
NUVISAN offers a large panel of disease models in mouse and rat across multiple oncology- and non-oncology indications.Where needed, we can help you with the testing of your molecules in newly in-house established disease models, or by cooperation with specialized CROs or academic institutions.
During lead optimization the goal is to guide a focused and fast optimization of lead structures towards a viable clinical candidate. Designing a tailor-made screening tree is a critical step to quickly identify and potentially overcome ADME liabilities, among others. In this phase, assay focus is on characterization metabolic stability (liver microsomes and hepatocytes), permeability and transporters, plasma protein binding, blood-plasma ratio, reversible CYP inhibition in major isoforms, irreversible inhibition in CYP3A4, CYP induction (HepaRG cells), phenotyping of drug metabolizing enzymes (CYPs, UGTs and non-CYPs), metabolite identification and structure elucidation (e.g. from hepatocytes, microsomes).
Furthermore, our in vivo platform provide high quality PK studies in mice and rats with microsampling from jugular-vein cannulated animals to complete PK profiles per animal. Depending on the compound profile and needs, our capabilities offer various study designs, including intravenous (bolus and infusion) and oral (intragastral) administration routs. Dosing of molecules may be in cassette (up to 3 molecules in 1 study) or as mono compound dosing. Tailor-made mechanistic studies for specific ADME questions can be provided: tissue distribution studies (cold compound) incl. excreta from the same animal, bile duct-cannulated rats, compound administration via portal vein infusion. Relative bioavailability (formulation research). Automated blood sampling is also possible for specific questions. State-of-the-art animal welfare standards.
Using AP/MALDI-HRMS, we can help you to understand the distribution and regional concentrations of your candidate drugs, drugs, metabolites and endogenous molecules in any type of tissue section. Our instrument platform will offer you various options, from sample preparation to MS Imaging data analysis. Complete packages from the animal studies to various tissues and molecular evaluation techniques can be discussed as a package.
We perform state of the art toxicity studies in rodents according to national and international guidelines and industry-leading animal welfare standards. Together with clinical pathology endpoints, histopathological diagnostics and toxicokinetics, we are able to identify target organs for toxic effects and establish a maximum tolerated dose to support the clinical program. Histopathological diagnostic: Our Laboratory offers all steps of slide preparation including trimming, tissue blocking, cutting and staining. Our board-certified pathologists (national and ACVP) with long experience in toxicological pathology conduct the histopathologic evaluation and support you in interpreting your results.
We support drug discovery programs through the identification and characterization of target engagement / pharmacodynamic biomarkers. Combined with PK data they can at this stage confirm the mechanism of action and contribute to the understanding of PK/PD relationships. We use a combination of disease-relevant non-clinical in vitro/ in vivo models complemented by studies in human clinical samples to ensure translatability of our findings. Target engagement / pharmacodynamic biomarkers are valuable read-outs to demonstrate the on-target activity of a novel clinical candidate in early clinical trials.
Established assay technologies include IHC, RNA-scope, Next Generation Sequencing, FACS, ELISA and MSD assays.