Identification of Patient Stratification Markers

Oncolines® Profiling is the parallel profiling of drug candidates on a panel of 102 human cancer cell lines. More than 200 cell lines are available for proliferation assays and other studies. The cancer cell lines are from diverse tumor tissue origin and have been characterized with regard to the mutation status of cancer genes and by gene expression analysis. Clients can order full panel profiling studies or cherry pick cell lines from the panel based on specific characteristics, such as tumor origin, gene mutations, or expression of certain cancer genes. The drug sensitivity of the Oncolines® cancer cell lines is determined in cell proliferation assays and correlated to the cancer gene mutation status of the cell lines. This yields novel candidate drug sensitivity biomarkers (Uitdehaag et al., 2019 and 2014).

These biomarkers are used as selection markers for patient stratification (Zaman et al., 2017), while the drug sensitivity fingerprint of compounds determined with Oncolines® Profiling is used for comparative analyses with other anti-cancer agents (Uitdehaag et al., 2016 and Kooijman et al., 2022) and for mechanism-of-action studies (Libouban et al., 2017). The Oncolines® cell lines are also the basis of drug combination screens (Uitdehaag et al., 2015).

In-Depth Analysis of Biological Mechanisms and Pathways

With flexible and tailored assay development we can focus on the biological pathways of interest. A wide range of cancer cells, immune cells and primary patient material are at our disposal. The proof of concept studies will boost the science of your projects.

Biochemical Characterization of Inhibitor-Target Interaction

Precision Medicine also concerns the precise targeting of your compound. We have determined the affinity of many small molecule kinase inhibitors on their respective drug targets through our surface plasmon resonance (SPR) platform ResidenceTimer™. A list of kinases that have been validated on our SPR platform using reference inhibitors can be found on our website and in our publications (Willemsen-Seegers et al., 2017). SPR and biochemical kinase profiling was used to differentiate rivoceranib, a VEGFR2 kinase inhibitor currently under review at the US Food & Drug Administration (FDA), from other VEGFR2 inhibitors (Jang et al., 2023). With SPR binding experiments, we also contributed to the discovery of Toll-like receptors as the molecular target of OM-85, a bacterial lysate used in clinical practice to reduce respiratory tract infections in children (Khameneh et al., 2024). We thus have substantial experience in the biochemical characterization of drug-target interactions for protein kinases, but also for other target classes.

Selective molecular drug-target interactions decrease the likelihood of off-target toxicity. The optimization of structure-activity relationships is facilitated by a variety of assays, including ResidenceTimer™ (Uitdehaag et al., 2017). The longer the residence time of a drug on its target, the longer the target is inhibited. The biochemical and kinetic selectivity of inhibitors form a basis for differentiation of drug candidates (Willemsen-Seegers et al., 2017). Further mechanistic understanding of the interactions can be provided through enzymatic activity assays, by looking at the thermal stability of a protein in the presence and absence of a compound and through resolution of drug-target crystal structures (Grobben et al., 2020).

About Symeres

Symeres is the leading mid-sized transatlantic Contract Research Organization for your drug discovery and development challenges.
With over 600 highly educated scientists in six locations in Europe and two in the USA, we offer best-in-class solutions for drug discovery and drug development, from small to medium-sized molecule hits. We are large enough to matter, and small enough to care.
Our services span across early stage hit finding all the way to the delivery of your early clinical drug substance API. Making Molecules Matter. Together.