Caco-2 Monolayer Assay

Service	Cell Line	Transporter	Technology	Probe Substrate	Reference Inhibitor
Caco-2 BCRP inhibitor assessment	Caco-2	BCRP	Monolayer Assay	Estrone 3-sulfate (E3S)	Ko143, Novobiocin, Fumitremorgin C (FTC)
Caco-2 BCRP/MRP2 inhibitor assessment	Caco-2	BCRP MRP2		Sulfasalazine	Ko143, MK-571, Benzbromarone
Caco-2 BCRP substrate assessment / Chemical inhibition	Caco-2	BCRP	Monolayer Assay	Estrone 3-sulfate (E3S)	Ko143, Novobiocin, Fumitremorgin C (FTC)
Caco-2 MDR1 inhibitor assessment	Caco-2	MDR1/P-gp	Monolayer Assay	Digoxin	Ketoconazole, Valspodar, Verapamil
Caco-2 MDR1 substrate assessment / Chemical inhibition	Caco-2	MDR1/P-gp	Monolayer Assay	Digoxin	Ketoconazole, Valspodar, Verapamil
Caco-2 MRP2 inhibitor assessment	Caco-2	MRP2	Monolayer Assay	CDCF-DA	MK-571
Caco-2 MRP2 substrate assessment / Chemical inhibition	Caco-2	MRP2	Monolayer Assay	CDCF-DA	MK-571
Caco-2 permeability testing	Caco-2		Monolayer Assay	-	-

Description

Monolayers based on Caco-2 cells (a human colon carcinoma cell line) express a wide range of transporter proteins on its cell membranes, similar to those of intestinal endothelium cells (Siissalo S et al. 2007, Calcagno AM et al. 2006), thus this cell line is ideal for intestinal absorption simulations. The utilization of Caco-2 cells has through the years become an industry standard for the investigation of intestinal absorption, permeability and drug-drug interactions (DDIs) (Oh DM et al. 2002.). Major efflux transporters that are expressed in the model are BCRP, MDR1 (P-gp) and MRP2, as well as several uptake transporters. Notable however is that Caco-2 cells from different strains in different labs may have distinct difference in expression and activity of efflux transporters and therefore working on a well characterized cell is important for getting a mechanistical understanding of the substrate nature towards any of these transporters.

Studies available:

Basic permeability testing in Caco-2
Determination of the compound class permeability using the Biopharmaceutical Classification System (BCS) for Biowaiver purposes according to ICH and FDA guidelines (Expected end of 2020)
Mechanistical studies to assess compounds in Caco-2 as substrate of
- BCRP (using inhibitor Ko143 or novobiocin, or Caco-2 KO cells)
- MDR1 (using inhibitors ketoconazole, valspodar or verapamil, or Caco-2 KO cells)
- MRP2 (using inhibitor MK-571, or Caco-2 KO cells)
Inhibitor assessment in Caco-2 on probe substrates of
- BCRP (estrone-3-sulfate or sulfasalazine)
- MDR1 (digoxin)
- MRP2 (CDCF-DA)

Caco-2 studies can be performed in different setups. SOLVO offers a number of standard setups, which differ in terms of the derivable information and cost. These standard setups serve as starting points to define the optimal final study parameters. All setups contain a standard number of controls (e.g. low permeability, high permeability, transporter function and inhibitor thereof).

These setups can be customized to suit your needs.

Learn more about the Caco2 Monolayer services.