P-gp Inhibition (P-gp-HEK Vesicles, N-methyl-quinidine Substrate) - US

Background Information:

P-glycoprotein (P-gp) or Multidrug Resistance Protein 1 (MDR1), gene symbol ABCB1, 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 in the blood-brain barrier. They translocate a wide variety of substrates across cell membrane, including endogenous and exogenous toxins and drugs. Therefore, the inhibition of P-gp by a candidate drug can lead to significant interaction with other drugs which are the substrates of P-gp. The assessment of P-gp 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 P-gp is using inside-out vesicles prepared from HEK293 cells stably expressing human P-gp. This assay uses LC-MS to quantify the amount of N-methyl-quinidine, a known P-gp 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