Ex vivo P-gp inhibition model

There is a strong evolutionary conservation between the insect blood brain barrier (BBB) and the mammalian BBB. This includes functional chemoprotective parallels between the human MDR1/P-gp transporter system and the insect Mdr65 transporter system [1]. EntomoPharm has developed an experimental ex vivo model based on the locust brain (Figure 1) for analyzing physiological properties of the BBB in the intact brain of locusts (Schistocerca Gregaria). The model can be used to screen small-molecule compounds for permeability and to identify P-glycoprotein (P-gp) interactions of drug leads [2]. The model can replace standard in vitro screen models in the early drug development screen cascade and supplement vertebrate models of BBB permeability.

In the ex vivo P-gp Locust BBB model the influence of P-gp inhibition on compound permeability is studied at constant test compound exposure of 1-10 μM and is independent of degrading enzymes, elimination and plasma protein binding. Data quality is high and the study outcome is always judged towards the response of an internal positive control.

Key model advantages:

1. The locust blood brain barrier is the only ex vivo model of BBB permeability
that is based on an intact natural biological brain barrier that retains its
biological integrity and control functions during the test procedure similar to
vertebrate in vivo BBB models.

2. The ex vivo P-gp Locust BBB permeability model can be used to identify
P-gp substrates and to rank BBB permeability in both single and multiple
dosing regimens.

3. P-gp identification by pharmacological inhibition of P-gp in the ex vivo P-gp
BBB permeability model avoids the complexities of multiple transporters by
focusing specifically on effect of P-gp efflux inhibition.

4. The P-gp Locust BBB permeability model permits test on ready made
stock solutions.

For more information please click on the link below to open a one-pager about the model:

Locust ex vivo Pgp inhibition model

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