Drug toxicity, often manifested as liver toxicity and cardiotoxicity, is a key reason for drug attrition. Identifying potential toxicity at an early stage in drug discovery can save both time and developmental costs, and most importantly reduce the likelihood of late stage failure.
Cyprotex is the ideal partner to assist you in understanding the toxic liability of your compounds using a panel of different techniques. We can help identify which compounds have the optimal ADME and safety profile to advance into the clinic. Our focus on state of the art technology and automation allow for high quality data to be generated rapidly and cost-effectively.
To that end, Cyprotex have invested in several high content screening (HCS) platforms that use automated fluorescence imaging to simultaneously analyze multi-parametric indicators of cytotoxicity. This improves the prediction of toxicological events and allows for a better understanding of the mechanisms of drug toxicity.
Our CellCiphr® technology was acquired from Cellumen in 2010. The technology provides a thorough assessment of potential mechanisms of toxicity using a HCS platform and links to exposure (Cmax) levels to understand the clinical relevance of the data. In 2013, we launched a new assay (eCiphr®Cardio) to evaluate cardiotoxicity in human iPS cell-derived cells using microelectrode array. This service has the advantage that it determines whole cell electrophysiology for all major ion channels in synchronously beating cardiomyocytes. Using the same microelectrode assay platform, we have also developed in vitro CNS cell-based assays (eCiphr®Neuro and eCiphr®Neuro-Human) to evaluate neuronal activity using rat primary cortical neurons or human iPSC-derived co-cultures of neurons and astrocytes.
Cyprotex offer a number of other services including reactive metabolite detection using trapping agents, a cell stress panel, drug-induced phospholipidosis and steatosis, lysosomal trapping, hemolysis, mitochondrial toxicity (mitochondrial biogenesis assay, Glu/Gal assay, functional mitochondrial toxicity assay and the mitochondrial respiratory complex assay), hERG inhibition using automated patch clamp, single end point cell viability endpoints (e.g., MTT, neutral red and LDH), apoptosis and necrosis assay using flow cytometry, toxicological gene regulation using qRT-PCR and a range of drug-drug interaction screens (available via Cyprotex ADME services). Cyprotex can also assess the potential genotoxicity of your compound using non-GLP screening protocols. These include the Ames Test, the in vitro MNT (CHO-K1), the in vitro MNT (TK6), the GreenScreen HC™ assay, or the in vitro Comet assay. Cyprotex can also offer a pH3 and pH2AX genotoxicity assay which can detect genotoxic liability as well as differentiate between aneugens and clastogens.
Cyprotex now offer services to analyze 3D microtissue or spheroid models using multi-parametric high content imaging or by assessing ATP content.
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