Primary Kidney Cells (aProximate™)
Around 50% of the pre-clinical, in- vivo screening of new drug molecules fail to predict subsequent human toxicity. Species differences in the pharmacokinetic and toxicokinetic profiles resulting from differences in metabolic enzymes and, in particular, transport proteins account for the majority of these differences. The consequence of the lack of predictiveness of current renal screening techniques are two-fold:
1: toxicity found in “first in man” studies is expensive at a late stage in the development pipeline
2: ‘false-positives’ in vivo rat/dog/mouse studies may lead to a promising drug which may have no toxicity in man being automatically disregarded in pre-clinical studies.
To address these issues, Abcellute have collaborated with Dr Colin D A Brown of Newcastle University to develop aProximate™, a validated model based on primary cultures of kidney proximal tubule cells. aProximate™ represents a major advance over any current cell-based standard approach. Developed on permeable filter supports it allows full bi-directional flux analysis. The unique primary cell nature of aProximate™ expresses the whole gamete of transporters and receptors of the native tissue including all renal drug transporters included in the ITC “white paper” and EMA guidelines. We have extensively characterised drug uptake, metabolism and secretion in these monolayers and their response to exposure to xenobiotics and physiopathological stimuli. Our models confirm that there are substantial differences in the molecular and functional profiles between human and non-human primary cells, which could account for the species-specific effects often observed.
aProximate™ expresses the full range of renal drug transporters invluded in the ITC White Paper and EMA Guidelines.
Figure 1: The Transmembrane Model allows bi-directional flux analysis
Figure 2: Cells express full range of Key Transport Proteins
at apical and basolateral membranes
For more information on aProximate™ please e-mail nathan.griffiths@abcellute.com with your full contact details and put aProximate™ in the subject heading.
