Discovery of Small Molecule Targeted Therapeutics

Finding Mechanistic Keys to Biomarker Discovery

NTRC uses cutting edge translational science to gain mechanistic understanding of the efficacy of our investigational drug candidates. The insights concerning sensitive patient populations and drug-target interactions drive an informed approach to clinical development.

NTRC’s Drug Discovery projects are available to pharmaceutical companies for in-licencing. Our projects are focused on innovative targets in precision oncology. We have a strong academic network that is leveraged to identify new and innovative approaches for small molecule drug discovery. NTRC is a privately owned biotech company based in the Netherlands.

  • Highly selective compounds

  • Designed to stay on-target for extended times

  • Targeting designated populations of cancer patients

Focus on Biomarker Identification

Targeted therapies exploit unique features of tumor cells, thereby permitting cancer specificity, while having limited effects on healthy cells. Many targeted therapies are genotype-selective, enabling the selection of patients most likely to respond by the detection of specific genomic alterations in tumors, such as gene amplifications, translocations, or point mutations. Well-known examples are the use of growth factor receptor kinase inhibitors in breast cancer patients with amplification of the HER2 gene (Higgins and Baselga, 2001), and inhibitors of a mutant form of the serine/threonine kinase BRAF in metastatic melanoma (Bollag et al., 2010). NTRC’s science platforms consist of robust in vitro assays to identify the mechanism of preclinical and clinical drug candidates. Our technologies provide in vitro proof of concept which facilitates the preparation of in vivo studies and clinical trials.

NTRC Therapeutics_Our Science. Technology platforms are focused on Precision Oncology

NTRC Precision Medicine Services

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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