OATP2B1 Transporter Assay (SLCO2B1)

The Organic Anion Transporting Polypeptide 2B1, or OATP2B1, is expressed on the sinusoidal (basolateral) membrane of human hepatocytes, the luminal (apical) side of intestinal enterocytes, the luminal (apical) membrane of brain capillary endothelial cells (blood-brain barrier), as well as in placenta, skeletal muscle, ovary, testis, spleen, and mammary glands.  Like other members of the OATP family, OATP2B1 has broad substrate specificity and can transport many therapeutic agents, such as statins, benzylpenicillin, fexofenadine, bosentan, and gluburide, as well as endogenous substrates such as bile acids and steroid hormone conjugates.  OATP2B1 can also be inhibited by many commonly used medications, including protease inhibitors (such as ritonavir), gemfibrozil, rifampicin, and cyclosporine.  As a result, clinically relevant drug-drug interactions could be mediated by OATP2B1 in the liver.

OATP2B1 is also known to be an absorptive transporter of drugs in the intestine.  Fexofenadine uptake is mediated by intestinal OATP2B1.  Individuals with a C1457T (Ser486Phe) polymorphism show significantly decreased fexofenadine absorption.  In addition, foods such as fruit juices can inhibit OATP2B1 and cause a decrease in fexofenadine absorption.  Other OATP2B1 substrates, such as celiprolol, also show altered absorption due to fruit juices and OATP2B1 polymorphisms.

OATP2B1 appears to have multiple binding sites.  OATP2B1-mediated transport of estrone-3-sulfate and pitavastatin have been shown to be inhibited by naringen, but fexofenadine transport is unaffected by naringen, perhaps due to distinct binding sites.  Uptake of estrone-3-sulfate can also be enhanced rather than inhibited when co-incubated with some compounds, such as progesterone or bromosulfophthalein, which can inhibit uptake of other OATP2B1 substrates (or inhibit at higher concentrations).

The current FDA and EMA guidance documents do not include testing investigational new drugs as potential substrates or inhibitors of OATP2B1.  However, OATP2B1 may contribute to drug-drug interactions in the liver.  In addition, OATP2B1 may have a much greater role in drug absorption in the intestine than previously considered, where OATP2B1-mediated uptake of drugs can be affected by foods and co-medications.

Optivia’s OATP2B1 Assay

Optivia offers OATP2B1 substrate and inhibition assays in CHO cells.  We offer a wide range of studies, from single concentration screens up to full kinetic studies that allow the determination of IC50 values for inhibitors, as well as Km and Vmax values for substrates.

OATP2B1 Transporter Assay

Relevance – Drug absorption in the intestine, drug-drug or drug-food interactions in the intestine, hepatic uptake Single or Multi-Transporter Model – Single
Transporter Type – Uptake Cell Model – CHO
Assay Type – Intracellular accumulation Exactly Matched Control Cells – No
Species – Human Probe Substrate – Estrone-3-sulfate
Subcellular Localization in Assay Model – N/A Inhibition Positive Control – Bromosulfophthalein

 Clinical & Regulatory Relevance

OATP2B1 may be important for the uptake of many pharmaceuticals in the intestine, where OATP2B1-mediated uptake can be altered by the presence of foods and co-medications.  OATP2B1 is also expressed in the liver, where it could potentially contribute to drug-drug interactions, although the current FDA and EMA guidelines focus on OATP1B1 and OATP1B3 rather than OATP2B1.

Applications & Therapeutic Areas

Drug uptake in the intestine, potential use in improving oral drug absorption by OATP2B1-mediated uptake, possible use in cancer chemotherapy, possible role in DDI.

Related Resources

OATP transporter-mediated drug absorption and interaction.

Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption.

Impact of genetic variation in OATP transporters to drug disposition and response.

Genetic polymorphisms of OATP transporters and their impact on intestinal absorption and hepatic disposition of drugs.

Current understanding of hepatic and intestinal OATP-mediated drug-drug interactions.

Oral drug delivery utilizing intestinal OATP transporters.

The expression and function of organic anion transporting polypeptides in normal tissues and in cancer.

Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.

Transporter-mediated drug-drug interactions.

Hijacking solute carriers for proton-coupled drug transport.