1 April 2008
We are pleased to inform you that SOLVO Biotechnology has added the new PEPT1 and PEPT2 uptake transporter assays to its PrediScreenTM portfolio and introduces new, cost effective Caco-2 assay packages available as contract screening services.
Uptake transporters, which are expressed in the cellular membranes of hepatocytes, intestinal epithelium, brain capillary endothelium and renal epithelium, are an increasingly recognized factor in drug absorption, distribution and excretion (ADME). A wide range of drugs has been reported to be transported by uptake transporters from different families or cause drug-drug interactions (DDIs) by inhibition of one or more uptake transporters.
The SLC15 family members PEPT1 and PEPT2 are responsible for the uptake of di- and tripeptides into cells. PEPT1 is mainly present in the apical membrane of enterocytes, the renal proximal tubule and is also detected in pancreas and liver. PEPT2 is mainly expressed apically in the proximal tubule epithelium and reabsorbs peptides from the primary filtrate. It was also detected in other tissues such as the lung and the blood-brain-barrier.
The cellular uptake assay is a simple method to measure the interaction of compounds with PEPT transporters. SOLVO Biotechnology offers two types of uptake transporter assays:
- 1. The standard indirect uptake transporter assay is a rapid and cost effective study to detect the interaction of test drugs with the respective uptake transporter. The assay studies whether the test drug inhibits the transport of a known, labeled (fluorescent or radioactive) substrate of the transporter; however, this assay does not reveal the type of interaction (substrate or inhibitory).
- 2. The non-standard direct uptake assay studies the uptake of the test drug in cells overexpressing the respective uptake transporter compared to parental cells. Cellular accumulation is studied using labeled test drugs or by LC/MS. Direct assay may confirm substrate nature of the test compound and determine the KM and Vmax of the transport.
Uptake Transporter assay portfolio at SOLVO Biotechnology available for screening services:
| Transporter | Reporter substrate | Reference inhibitor | Cell type | Negative control |
| OATP1B1 (SLCO1B1) | 3H-Estrone-3-Sulfate (0.1 µM) | Cerivastatin (100 µM) | CHO | Parental cells |
| OATP1B3 (SLCO1B3) | Fluo-3 (10 µM) | Fluvastatin (30 µM) | CHO | Parental cells |
| OATP2B1 (SLCO2B1) | 3H-Estrone-3-Sulfate (1 µM) | Fluvastatin (10 µM) | MDCKII | Parental cells |
| rat Oatp1a1 (Slco1a1) | 3H-Estrone-3-Sulfate (1 µM) | Ketoconazole (200 µM) | CHO | Parental cells |
| NTCP (SLC10A1) | 3H-Taurocholate (2 µM) | Taurochenodeoxycholate (100 µM) | CHO | Na+ free buffer |
| rNtcp (Slc10a1) | 3H-Taurocholate (2 µM) | Taurochenodeoxycholate (100 µM) | CHO | Na+ free buffer |
| PEPT1 (SLC15A1) | Gly-Sar (2 µM) | Tyr-Phe (200 µM) | CHO | Parental cells |
| PEPT2 (SLC15A2) | Gly-Sar (2 µM) | Cefadroxil (200 µM) | CHO | Parental cells |
As part of SOLVO PrediScreenTM portfolio, new multi-level Caco-2 packages are now available to investigate permeability, specific transporter interactions and DDIs. Each package is provided at three different levels: from the cost-effective basic setup, through the informative extended layout, to the more complex assembly based on the draft FDA guidance.
- Permeability assessment: Passive permeability (PAPP) and efflux ratio determination on Caco-2 monolayers at one (Basic setup) or more (Extended setup) concentrations.
- Specific transporter interactions assessment: Permeability assessment in the presence and absence of specific inhibitors for P-gp and/or BCRP at one (Basic setup) or more (Extended setup) concentrations.
- DDI assessment: Study P-gp mediated DDIs by measuring inhibition of digoxin transport across Caco-2 monolayers at one or multiple concentrations (IC50 determination).
With our best regards,
SOLVO Biotechnology
Business Development Team
CONTACT INFORMATION:
SOLVO Biotechnology
E-mail:
web: www.solvo.comPhone: +36-23/503-940 Fax: +36-23/503-941 2 Gyár St. H-2040 Budaörs, HUNGARY
SOLVO distributors:
in US and Canada: XenoTech LLC www.xenotechllc.com,
in Europe: SOLVO and Tebu-bio: www.tebu-bio.com,
in Japan: Nosan www.nosan.co.jp,
in India: Krishgen: www.krishgen.com
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