SynergyFinder™

Identification of Synergistic Combinations

Synergy Drug Screening for Combination Treatment

SynergyFinder™ helps to ensure that new therapies are combined in the best way possible. Many cancer therapies are applied as combination therapies. To identify the right combination of your lead compound with standards of care or new drugs, NTRC has developed SynergyFinder™.

  • The studies are scalable from 1 to 1,000 combinations

  • Cell proliferation assays, using full dose response testing, are performed for single agents and mixtures

  • Fixed Ratio experiments allow IC50 based scoring of synergy
  • Dose-based synergy is determined by curve shift analysis and CI Index (Chou-Talalay equation)

  • Effect-based synergy is determined by quantification of shifts in the maximum effect, using Bliss-scoring

  • IC50 profiles of more than 180 standards of care and experimental therapeutics are available to propose mixtures

  • Your choice of cancer cell lines
SynergyFinder Trametinib + Dabrafenib Curves incl CI Waarde
Curve shift due to synergistic interaction for trametinib (Mekinist®) and dabrafenib (Tafinlar®). This combination is FDA approved for BRAF mutant cancers.

Unbiased High Throughput Screening for Novel Synergistic Hits

Screening 600 to 1000 combinations within a short turnaround time: your drug candidate is tested against the full library of 180 therapeutics in selected cancer cell lines within 12 weeks. If you prefer a smaller subset, we have an exemplar library of 42 therapeutics for the mechanisms that are covered in the full library. The exemplars represent the well-known and newly investigated anti cancer drugs classes. Of course, the choice of combinatorial therapeutics and cell lines is up to you.

  • Broad, unbiased synergy screening may show unexpected novel synergistic combinations

  • 42 exemplars have been identified for anti cancer drugs classes including PARP, CDK4/6 and bromodomain inhibitors and clinically validated mechanisms of action

  • Reproducibility is covered by independent repeat experiments for synergistic combinations

  • A screen typically takes 8-12 weeks until delivery of final report

Targeted Synergy on the basis of Gene Mutation Biomarkers

You may prefer to test a selection of standards of care or experimental therapeutics to combine with your drug candidate. We can assist in selecting mixtures on the basis of biomarkers and targeting, as described by Uitdehaag et al. (2015) – the choice is yours. We are happy to provide cost-free consultation if desired.

  • A screen takes 6 weeks until delivery of final report

Dose-Based and Effect-Based Synergies

The curve shift analysis determines synergy as a decrease in dose to achieve the same effect (Dose-based). The Bliss approach bases synergy on an increase in the maximum effect (Effect-based). The two methods have been merged into one approach, so that a comprehensive view on synergistic effects is generated. An advantage of the approach is that data interpretation is based on full dose response curves of the single agents and the mixtures. This approach takes the sigmoidal nature of the curves into account, covering exponential effects that may be overlooked in a dose-matrix approach.

  • Synergistic effects are quantified by CI value and Bliss score

References

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

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