Design and synthesis from hit to clinical candidate
An experienced interdisciplinary team will work with you on your next clinical candidate.
Drug discovery is an interdisciplinary science where experience is key. Our Medicinal Chemistry team combines over 150 years of relevant experience in the pharma industry. We also partner with leading CROs for specific biological platforms, offering an integrated solution to your Drug Discovery needs.
Symeres delivers high-quality medicinal chemistry services to advance your drug discovery programs: from hit identification to lead optimization and nomination of a clinical candidate. Our team combines highly experienced leadership and project scientists with extensive resources, such as parallel synthesis and purification, supported by our computational chemistry and in vitro ADME platform. This combination of expertise and infrastructure allows the rapid multiparameter expansion and optimization of compound series.
For integrated drug discovery programs, we have strategic relationships with a network of high-quality partners with expertise in biochemical, cellular and high-content assay development, high throughput screening; structural biology; biophysics and pharmacokinetics. Our network of industrial centers of excellence are accessed under a simple contractual arrangement and with a single project management structure as required by the project.
Hit Generation and Hit-to-Lead Activities
Symeres has a strong track record in the validation and expansion of hits derived from different screening platforms, including those from high-throughput screens (HTS), fragment screens, DNA-encoded libraries and AI based virtual screens. We are also experienced in deriving new starting points based on literature and patent data.
We have ample experience in validating and prioritizing HTS hits, taking into account principles of lead-likeness, synthetic feasibility and intellectual property. Our parallel chemistry and purification platform can play a decisive role in rapid hit expansion, developing both structure-activity and structure-property relationships for hit series. This rapid analog generation allows project teams to make informed decisions on priority and future strategy based on a solid data package.
In fragment-based drug discovery, chemical starting points are often weak binders, albeit with high ligand-efficient efficiency and structural information. Our medicinal chemistry team includes several experts with significant industrial experience of the unique aspects of fragment-based approaches, including the application of biophysical and protein-ligand structural data.
Lead optimization requires fine-tuning multiple parameters. Symeres has an excellent track record of progressing programs through to candidate selection.
Clients oftenapproach us with chemical starting points requiring optimization of a single or multiple parameters, such as solubility, hERG, CYP inhibition etc.
Our in-house SAR database solutions, coupled to DataWarrior and Schrödinger’s LiveDesign interfaces, allow us to effectively mine and analyze project data to efficiently design analogues and progress your lead series toward candidate selection. In many cases we integrate our parallel synthesis and purification infrastructure, generating arrays of analogs to rapidly build structure-activity and structure-property relationships, which we use to design the next generations of ligands.
From bioisosteric replacements to interactive structure and ligand-based drug design, computational chemistry is an integral part of many of our medicinal chemistry projects. Our computational chemists have a solid background in synthetic chemistry and factor synthetic feasibility into their molecular design activities.
At Symeres, we develop modeling approaches tailored to customer requirements. Our arsenal of molecular modeling software includes Spark, MOE, and Maestro, and we employ state-of-the-art protein and data visualization software to generate insight into how lead molecules bind to the target protein, either via experimental data or molecular docking.
Our Medicinal Chemistry teams employ advanced data visualization and analysis tools, such as DataWarrior and LiveDesign, which allow for expert property interrogation, trend studies, and R-group analyses. Our workflows allow our chemists to submit design ideas for automatic docking to filter and refine their design hypotheses.
We offer computational chemistry as an integrated component of any medicinal chemistry project and as a stand-alone service.
Rapid Analog Synthesis
Symeres has a dedicated team for the design and synthesis of compound arrays, with a focus on novel sp3-rich, 3-dimensional scaffolds.
Parallel array synthesis is a powerful tool to rapidly explore the chemical space around a hit compound. At Symeres, we have developed streamlined workflows to optimize our library synthesis. The equipment our chemists use is semi-automated, allowing both a speedy process and room for customization. We have multiple platforms available to adapt the setup of the library to your specific needs, whether this is a few compounds or a few hundred.
Integrated Drug Discovery
Through an established centers of excellence network, Symeres enters into a single contractual agreement with the client that allows access to leading European providers.
Symeres has a strong European network of centers of excellence to provide integrated drug discovery for our clients. Central to this is a strategic alliance with Axxam [www.axxam.com], based in Milan, Italy, which is a world-class provider of in vitro assay development, screening, and compound profiling services. The combined platforms of Symeres and Axxam, accessed under a single contractual agreement, provide the core upon which to build gene-to-candidate Discovery programs. Program-specific solutions can also be provided for areas, such as biophysics, pharmacokinetics, pharmacology models, and structural biology.
We can support your multiparameter medicinal chemistry optimization even further with our in vitro ADME profiling platform.
The following assays are available in house, with further systems either being brought online or sourced via third parties:
- Kinetic solubility (LC-UV)
- Thermodynamic solubility
- Lipophilicity (ElogD)
- Chemical stability
- PAMPA (parallel artificial membrane permeability assay);
- Plasma stability
- Microsomal and hepatocyte stability from different species.
- Metabolite identification using high-resolution mass spectrometry (Q Exactive Orbitrap, Thermo)
- CYP inhibition screening studies to determine possible drug interactions of compounds (CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4)
Our in vitro ADME department also serves as a stand-alone contract research laboratory, where we offer tailor-made assays. In vivo facilities are available as part of our integrated drug discovery services from high-quality third parties under a single contract with us.
In addition to the above-mentioned services, we can now support your projects further with high-quality ADME-Tox/In vivo DMPK services provided by Admescope. It is crucial to conduct the right studies at the right time to save costs and reduce the risk for failure at the later stages of the project. Admescope’s services cover a wide range of tailorable assays to support customers' needs in an optimal way.
The available services include:
In vitro metabolism
High-quality in vitro metabolism services are available to evaluate the metabolic fate of the compound in liver or extrahepatic tissues. The samples are analysed with state-of-the-art UPLC/HR-MS equipment.
- Metabolic stability
- Metabolite identification and profiling
- Identification of metabolising enzymes
- Non-CYP mediated metabolism
- Extrahepatic metabolism
- Metabolite production and NMR identification
- Reactive metabolite screening
- Acyl-Glucuronide reactivity
- Stability in plasma, buffer or biorelevant media
- IVIVE & PBPK modelling
Safety metabolism studies help you to confirm that the exposure to human metabolites is adequate in preclinical safety species, or to effectively identify potential MIST (metabolites in safety testing) issues in time, through a battery of different types of studies
- Metabolite profiling and characterisation in pre-clinical species
- Human metabolite profiling and characterisation (FIM, SAD, MAD)
- Human MIST analysis (MAD + preclinical safety species)
- Metabolite profiling and characterisation in radiolabeled human ADME study
- Metabolite profiling in milk secretion studies
In vivo drug metabolism and pharmacokinetics
The in vivo DMPK services cover a variety of animal experiments in several species. In-house rodent PK studies are carried out in AAALAC accredited animal facilities and studies with other species are completed together with selected European in-life partners.
Evaluating drug-drug interaction risk is a crucial part of drug safety evaluation required by the drug regulatory authorities. The available services cover the identification of metabolising enzymes, enzyme inhibition and enzyme induction assays, as well as transporter-mediated drug-drug interactions.
- CYP inhibition
- UGT inhibition
- Inhibition towards other metabolising enzymes
- CYP induction
- UGT induction
- Transporter interactions
Permeability and transporters
Several assays are available for evaluating permeability and identifying drug transporter substrates or inhibitors.
Physicochemistry and binding
Physicochemical parameters give information about the “drug-likeness” of the compound, with respect to absorption from the intestine. Information about these properties is also valuable when planning optimum conditions for other in vitro ADME assays.
- Plasma protein binding
- Red blood cell binding
- Tissue binding
- Microsome/Hepatocyte binding
In vitro toxicology
Information about in vitro toxicity early on during the drug discovery process support your internal decision making. The available in vitro toxicology assays are planned for cost-efficient screening with low compound consumption and cover the most commonly faced toxicity related challenges.
- Cardiotoxicity screening
- Genotoxicity screening
- Cytotoxicity screening
- Mechanistic toxicity assays
- Hematologic toxicity