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ciPTEC - The solution to reduce the risk of drug failure during the clinical phase of Drug development

 

During clinical stages of drug development, 20 to 30% of drugs fail due to renal toxicity.
 
Most of the current screening models can not accurately mimic the human kidney,
too many toxic compounds enter the late stage of drug development.
 
Further, current predictive kidney research models available are either accurate and not scalable, or scalable and inaccurate, but not both.
 
In order to bring more successful drugs to the market, Cell4pharma has developed a highly
accurate and stable renal cell line: ciPTEC, to enable researchers to accurately identify and eliminate nephro-toxic compounds in the pre-clinical development stage.
 

ciPTEC cell line technology

ciPTEC (conditionally immortalised human Proximal Tubule Epitelial Cell line) is a human renal cell line that mimics the proximal tubule cells of the kidney.

These cells are a main target for drug-induced kidney injury, caused by their role in highly efficient transport of drugs and toxic compounds from the bloodstream into urine.

The most relevant drug transporter proteins involved in this process are stably and functionally expressed in our cell models.

 

The technical expertise of Cell4pharma, resulted in the development of 3 ciPTEC cell lines expressing the most relevant renal drug endogenously.

ciPTEC 14.4 cell line

ciPTEC 14.4 has been stably transfected by SV40T and hTERT, subcloned and well-characterized. Expressing proximal tubular markers alkaline phosphatase, di-peptidiyl peptidase IV and ZO-1. Maintained transport functionality for sodium-dependent phosphate reabsorption, megalin-cubilin receptor mediated endocytosis, organic cation transport (SLC22A2); p-glycoprotein (ABCB1), multidrug resistance protein 2/4 (MRP2/4), breast cancer resistance protein (ABCG2) and a range of metabolic enzymes (1).

ciPTEC 14.4 cell line

ciPTEC OAT 1

Based on ciPTEC 14.4, including expression and functional uptake via organic anion transporter 1 (OAT1) (SLC22A6) (4)

ciPTEC OAT 1

ciPTEC OAT 3

Also based on ciPTEC 14.4, this cell line is including expression and functional uptake via organic anion transporter 3 (OAT1) (SLC22A6). Both ciPTEC OAT 1 and ciPTEC OAT 3 has been achieved  via lenti-viral transfection (4).

ciPTEC OAT 3

 

 

ciPTEC Applications

ciPTEc cell lines can be used:

From Early Drug Discovery: High-Throughput NephroToxicity screening (2)
To preclinical studies and Clinical development : Mechanistic assay studies
 

And for any type of research organization

Academic Research:

Ideal tool in the fields of pharmacology, toxicology, nephrology, pathology and renal physiology.
Highly accurate renal toxicity research : Realistic cellular Response to toxic exposure
Easy to use following standard culturing protocols
 

Biotech and Pharma

Gain Mechanisitic insights: Stay focused on the most promising compounds at an early stage
Reduce losses during clinical stages of drug development

CRO

More accurate and stable results to your clients : Realistic cellular response to toxicant exposures
Cutting edge services: Broad range of cell-based assays based on ciPTEC (Drug interaction studies,
IC50 determinations, toxicity studies, gene expression analysis, miRNA biomarker screenings,
ciPTEC allows the detection of specific biomarkers upon toxicant exposures.)
 

 

Regulatory Guidelines for Drug Elimination Routes

The recent guidances for the pharmaceutical industry published by the Food and Drug Administration (FDA) in 2017 and the European Medicines Agency (EMA) in 2013 recommend that drug development should include identification of elimination routes via drug transport proteins and characterize drug-drug interactions (DDI). These include the investigation of renal drug transport studies at the sites of p-glycoprotein (Pgp), breast cancer resistance protein (BCRP), multidrug and toxin extrusion transport 1 and 2 (MATE1, MATE2-k), organic cation transporter 2 (OCT2) and organic anion transporter 1 and 3 (OAT1, OAT3). All transporters are present in our ciPTEC platforms.

ciPTEC Publications

Cited in more than 70 publications, ciPTEC cell lines demonstrated to be valuable in different research topics.

Check some key papers below:

    1- Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters

WIlmer et al. Cell Tissue Res (2010) 339:449–457

    2- A novel multi-parametric high content screening assay in ciPTEC-OAT1 to predict drug-induced nephrotoxicity during drug discovery

SJogren et al, Arch Toxicol (2018) 92 :3175–3190

    3- Screening of Drug-Transporter Interactions in a 3D Microfluidic Renal Proximal Tubule on a Chip

Vriend et al, The AAPS Journal (2018) 20: 87

    4- A Human Renal Proximal Tubule Cell Line with Stable Organic Anion Transporter 1 and 3 Expression Predictive for Antiviral-Induced Toxicity

Niskens et al, The AAPS Journal (2016) 18:465–475

    5- Implementation of a Human Renal Proximal Tubule on a Chip for Nephrotoxicity and Drug Interaction Studies

Vormann et al. J Pharm Sci (2021) 3549(21)

 

 

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