Discovery of Precision Oncology Drugs

Finding the Informed Route, Proof of Concept to Clinic, with In Vitro Cell-Based Assays

NTRC provides fee-for-services to pharmaceutical and biotech companies and academic institutions worldwide. It is our mission to help you with precision medicine and to find a mechanistic hypothesis before entering the clinic. Our technologies focus on robust assays to identify the mechanism of preclinical and clinical drug candidates. Our technologies provide in vitro proof of concept for the preparation of in vivo studies and clinical trials.

We can study a wide range of cancer cells, primary patient material and immune cells in vitro, in isolation and in co-culture, after exposure to monotherapy and combination therapy. Furthermore, we perform in-depth mechanistic analyses and biochemical drug-interaction studies (e.g. using Biacore and LC-MS/MS).

Reproducible Results, Short Timelines, Swift Communications

We deliver reproducible results that are adapted to your specific needs with a short delivery time. Direct contacts between our staff and sponsors result in efficient scientific and technical support. We provide cost-free consultation on next steps in research if desired by the sponsor.

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. Clients of NTRC 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 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 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.

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).

Quality. Flexibility. Short Turnaround Time.

References

Uitdehaag et al. (2019) Combined cellular and biochemical profiling to identify predictive drug response biomarkers for kinase inhibitors approved for clinical use between 2013 and 2017, Molecular Cancer Therapeutics, 18 (2):470-481.
https://mct.aacrjournals.org/content/early/2018/10/31/1535-7163.MCT-18-0877

Uitdehaag et al. (2014) Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use, PLOS ONE, 9 (3):e92146.
https://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0092146

Zaman et al. (2017) TTK inhibitors as a targeted therapy for CTNNB1(β-catenin) mutant cancers, Molecular Cancer Therapeutics, 16 (11):2609-2617.
https://mct.aacrjournals.org/content/early/2017/07/27/1535-7163.MCT-17-0342

Uitdehaag et al. (2016) Cell panel profiling reveals conserved therapeutic clusters and differentiates the mechanism of action of different PI3K/mTOR, Aurora kinase and EZH2 inhibitors, Molecular Cancer Therapeutics, 15 (12):3097-3109.
https://mct.aacrjournals.org/content/early/2016/09/01/1535-7163.MCT-16-0403

Libouban et al. (2017) Stable aneuploid tumor cells are more sensitive to TTK inhibition than chromosomally unstable cell lines, Oncotarget 8 (24):38309-38325.
https://doi.org/10.18632/oncotarget.16213

Uitdehaag et al. (2015) Selective Targeting of CTNNB1-, KRAS- or MYC-Driven Cell Growth by Combinations of Existing Drugs, PLoS ONE, 10 (5):e0125021.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125021

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