[2013 Society of Toxicology Poster] - Phenotypic Approaches Defining Toxicity Mechanisms

[2013 Society of Toxicology Poster] - Phenotypic Approaches Defining Toxicity Mechanisms
Version:
2013

File Name/Number:
SOT2013

Year:
2013

Improving the safety of drug candidates that enter clinical development requires assays that are more predictive of human outcomes. The BioMAP® platform uses human primary cells to model complex aspects of disease and tissue biology and can be applied to better understand biological mechanisms that underlie drug adverse effects. Here we present the analysis of several anti-inflammatory kinase inhibitors, including inhibitors of p38 MAPK, Jak kinase (tofacitinib) and Syk kinase (fostamatinib) tested in a panel of 12 BioMAP systems covering a broad range of human biology. Specific effects of these compounds in BioMAP assays modeling aspects of wound healing and vascular biology appear to correlate with certain side effects of these drugs in patients, including skin rash (p38 MAPK), gastrointestinal perforations (Jak), and hypertension (syk). These in vitro effects may be useful in screening lead candidates prior to testing in animals or humans.