Our Science is Tailored Around the Patient

Small Molecules that are Targeted for Patient Populations

Precision medicine is tailored to the individual patient instead of a one‐drug‐fits‐all model. By finding exquisitely sensitive cancer subtypes and developing highly selective therapeutics, the therapeutic efficacy of a drug or drug combination can be enlarged, leading to a much greater chance of success in clinical trials.

NTRC’s mission is to develop targeted small molecules for cancer therapy. Our science platforms deliver proof of concept via biomarker identification using advanced bioinformatics and drug-interaction studies. We aim to find the informed route to the clinic for our highly selective inhibitors with prolonged pharmacological effects. Clinical development of our inhibitors is driven by mechanistic hypotheses.

NTRC - Our Science - Visual

The science platforms are applied by NTRC for the discovery of targeted small molecule drug candidates, see Projects. Our vision and approach towards precision medicine is also available for clients via NTRC’s Precision Medicine Services.

Scientific References to NTRC’s Science

We take pride in our results that are on the cutting edge of new translational science. The work has been shared with the research community via peer reviewed papers. An overview of papers can be accessed here and some examples are given below. Furthermore, NTRC’s technology platforms have been cited in scientific papers and on poster presentations by e.g. Puma Biotechnology, Bayer, PIQUR, Prinses Máxima Center, University of Basel, and others.

  • Libouban et al. (2017) Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines, Oncotarget, 8 (24):38309–38325. (Affiliations: Netherlands Cancer Institute, NTRC)

  • Zaman et al. (2017) TTK inhibitors as a targeted therapy for CTNNB1 (-catenin) mutant cancers, Molecular Cancer Therapeutics, 16 (11):2609-2617.

  • Uitdehaag et al. (2017) Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity, Journal of Molecular Biology, 429:2211-2230.

Finding Mechanistic Keys for Biomarker Discovery

In line with our vision on precision oncology, we apply the technology platforms to help cancer researchers to uncover mechanistic hypotheses for progressing to the clinic. Website www.oncolines.com informs you about the cell-based services and www.residencetimer.com presents the biochemical services.

Website Oncolines.com

Learn About Our
Cell-Based Services

oncolines.com

Identification of Patient Stratification Markers

Oncolines™ consists of the parallel profiling of drug candidates on a panel of 102 human cancer cell lines. 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. 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 in Oncolines™ is used for comparative analyses with other anti-cancer agents (Uitdehaag et al., 2016) 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 focus on the biological pathways of interest. Using a wide range of cancer cells, immune cells and primary patient material, the proof of concept studies will boost the science of drug discovery projects.

Website Residencetimer.com

Learn About Our
Biochemical Services

ResidenceTimer.com

Biochemical Characterization of Inhibitor-Target Interaction

Precision medicine also concerns the precise targeting of your compound. Selective molecular drug-target interactions decrease the likelihood of off-target toxicity. The optimization of structure-activity relation is facilitated by a variety of assays, such as ResidenceTimer™ for the determination of the target residence time of a drug on its target (Uitdehaag et al., 2017). The longer the residence time, 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 by looking at the thermal stability of a protein in the presence and absence of a compound and resolution of drug-target crystal structures (Grobben et al., 2020).

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