BCRP Inhibition (BCRP-HEK Vesicles, Estrone 3-sulfate Substrate) - US

Background Information:

Breast Cancer Resistance Protein (BCRP), gene symbol ABCG2, is an ATP Binding Cassette (ABC) transporter that uses ATP to transport substrates across the cell membrane (efflux). They are expressed in a variety of organs, such as the intestine, liver, kidney, and brain. They translocate a wide variety of substrates across cell membrane, including endogenous and exogenous toxins and drugs. Therefore, the inhibition of BCRP by a candidate drug can lead to significant interaction with other drugs which are the substrates of BCRP. The assessment of BCRP inhibition potential is one of the key assays in Drug Interaction Assessment recommended by regulatory agencies for all drug candidates. An effective way to assess the inhibition of BCRP is using inside-out vesicles prepared from HEK293 cells stably expressing human BCRP. This assay uses LC-MS to quantify the amount of Estrone 3-sulfate, a known BCRP substrate, accumulated inside the vesicles in the presence and absence of the test compounds in 96-well plates to determine the inhibition effect of the test compounds. The compounds can be tested at 1 concentration (n=2) for screening or at multiple concentrations (n=2) for IC50 determination.

Family:

Transporter

Sub Family:

ABCG

Class:

ABC

Organism:

Human

Cell Type:

HEK293