Screen your test compounds for potential nephrotoxicity risk
Glomerular filtration in the kidneys is the primary mode of drug excretion (1), making this organ highly
vulnerable to drug-related injury. The renal proximal tubes, in particular, play a major role in the
elimination of drugs and their metabolites, and drug-induced damage to this region can subsequently
result in acute kidney injury. Predicting the potential nephrotoxicity of a drug in preclinical stages is thus
crucial however remains difficult; nephrotoxicity is typically detected only in late, clinical stages (ref?).
Our renal toxicity screening assay overcomes these challenges by utilizing human-derived conditionally
immortalized proximal tubular epithelial cells (ciPTEC), which stably express a large host of functional
enzymes and transporters used by the proximal tubes in vivo (2) for drug elimination.
ciPTEC cells are cultured under optimal conditions to stimulate cellular differentiation and formation of
an epithelial monolayer. Validation is achieved via… The cells are then exposed to increasing
concentrations of test compounds for xxx minutes/hours. Toxicity is subsequently evaluated by
determining ATP concentrations, as a marker of cell viability, in treated versus untreated cultures. High
throughput screening in 384-well plates available upon request.
(1)Le, J. Drug Excretion. Merck Manual….
(2) Wilmer et al (2010) Novel conditionally immortalized proximal tubule cell line expressing
functional influx and efflux transporters…