SIGNATOPE´s testing service is offered to the pharmaceutical industry and CROs in 3 areas:
During the lengthy process of drug development, comprehensive tests need to be carried out to analyse organ toxicity. This includes mandatory tests in different animal species such as rodents and dogs (mainly for liver and kidney toxicity). Such tests must comply with specifications stipulated by the FDA, the ICH and the EMA. Besides acute toxicity, long-term toxicity, toxicokinetics and pharmacokinetics, and organ toxicity have to be tested to detect potential side effects on the cardiovascular and nervous systems, the lung, liver and kidney.
FDA’s Critical Path Initiative and the Innovative Medicine Initiative foster research to identify novel biomarkers that can predict organ damage early on. Tests for such markers are likely to become recommended for the approval of new drugs.
Translational safety biomarkers | SignaTOX |
SIGNATOPE is currently developing immunoassays for drug-induced kidney, liver, vascular and pancreas injury. The testsystem is the only method capable of quantifying identical protein biomarkers in all species using identical tests in the preclinical and clinical phases. Standardized cross-species assays will streamline test procedures in pre-clinical and clinical development and make cross-validation of different tests obsolete.
XENObiotics | SignaXENO |
Drugs are predominantly metabolized in the liver. The cytochrome P450 family (CYP) is involved in the oxidative (phase I) metabolism. In the second phase, these metabolites are modified by glucuronosyl- and sulfotransferases (phase II enzymes). Finally they are actively eliminated by transporters (phase III). These proteins significantly affect the bioavailability of drugs. Hence, new substances need to be tested for their potential to induce such enzymes and transporters. The FDA recommends using mRNA profiling to assess the induction of cytochrome P450 in preclinical studies.
However, SIGNATOPE offers protein-based assays, because protein levels have a higher predictive value. Our SignaXENO assays allow to measure 100s of samples per week, using less than 20 μg of human hepatocyte material. This is a 50-fold improvement in sample throughput and tissue usage compared to other methods.
Currently we have established assays for Cytochrome P450 isoforms 1A1, 1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2E1, 2D6, 3A4, 3A5, 3A7 and CPR.
This is the full assay list:
Assay and Antibody Development | SignaXIM |
SIGNATOPE provides project-oriented assay development services to pharmaceutical and academic partners.
More than 150 proprietary antibodies towards short terminal epitopes have been developed so far. This allows us to enrich thousands of different peptides in the digested proteome of a single species. The combination of SIGNATOPE´s antibodies and the high sensitivity and specificity of mass spectrometers allows us rapid assay development.
Moreover, SIGNATOPE provides unique monoclonal and polyclonal antibody development services for the application mass spectrometry-based immunoassays (e.g. ImmunoMALDI, …). Unique epitope selection tools, affinity screening methods, clone selection based on slow k , antibody purification strategies and array-based epitope characterization tools provide unbeaten success rates.
Gautier J. C., Zhou X., Yang Y., Gury T., Qu Z., Palazzi X., Leonard J. F., Slaoui M., Veeranagouda Y., Guizon I., Boitier E., Filali-Ansary A., van den Berg B. H., Poetz O., Joos T., Zhang T., Wang J., Detilleux P., and Li B. (2016) – Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin. Toxicology and applied pharmacology 303, 1-10
Frederik Weiß, Helen S. Hammer, Kathrin Klein, Hannes Planatscher, Ulrich M. Zanger, Agneta Norén, Christine Wegler, Per Artursson, Thomas O. Joos and Oliver Poetz (2018) – Direct Quantification of Cytochromes P450 and Drug Transporters—A Rapid, Targeted Mass Spectrometry-Based Immunoassay Panel for Tissues and Cell Culture Lysates. Drug Metabolism and Disposition April 2018, 46 (4) 387-396