Phosphoproteins and Cytokines
At Sygnature Discovery, we have developed a wealth of expertise in the identification and validation of pharmacodynamic (PD) biomarkers which can be applied to all phases of the drug discovery process from early preclinical studies through to the clinic. Examples of such PD biomarkers include phosphoproteins and cytokines.
PD biomarkers provide a quantitative measurement of the effects of a drug on the target. These readouts therefore help define the link between dosage of a compound, the biological response and the therapeutic benefits observed in the clinic. A PD biomarker will address whether a drug is modulating the intended target, the biological impact of modulating this target and the optimal drug dosing and scheduling regimen.
The path to the discovery of PD biomarkers is dependent on the nature of the drug-target interaction. Our experienced scientists here at Sygnature Discovery can help you develop appropriate biomarkers to diagnose or support your therapeutic indication. A range of assay types and platforms can be used to explore potential biomarkers, from Proof of Mechanism (POM) biomarkers to support PK/PD studies, gene expression profiling for patient segmentation, through to Proof of Concept (POC) biomarkers to support clinical efficacy. Our flexible and collaborative approach will ensure that your team at Sygnature Discovery delivers an efficient and robust PD biomarker fit for your purposes.
Examples of PD biomarkers include:
- Gene Expression
- Phosphoproteins and cytokines
Protein kinases represent an important class of drug targets. A classical method to measure the modulation of a protein kinase is to measure the phosphorylation of their (patho)physiological substrate. At Sygnature Discovery, we will customize the assay and select the best platform to measure substrate phosphorylation to meet your needs from immunoblotting to ELISA/AlphaLISA to flow cytometry. For projects that would benefit from simultaneously monitoring the phosphorylation status of multiple signalling intermediates, we can explore the development of assays using the MagPIX which allows up to 50 analytes to be measured in a single sample.
Cytokines are an important group of PD biomarkers for therapies aimed at modulating the immune response. Cytokines are released into circulation by leukocytes and thus, can be easily measured in a broad variety of biological samples including whole blood. There is a broad spectrum of cytokines with varying actions from pro-inflammatory to anti-inflammatory. The nature of the cytokines regulated by new therapies is highly dependent on the leukocyte population involved in the disease and expression of the drug target. At Sygnature Discovery, we will work with you to define the most appropriate cytokine(s) panel to be measured and then tailor the assay to meet the needs of your project. We have several technological platforms that can be used depending on requirements. For projects in which measuring one or two cytokines is sufficient, ELISA and/or AlphaLISA would be a cost-effective approach. However, we can also measure a large panel of cytokines using the MagPIX which allows up to 50 analytes to be measured simultaneously in a low volume (50 ml) of a single sample. This latter approach provides a cost-effective method to obtain a more complete picture of the effects of a drug on limited sample material.