Cell lines

HEK293/MRP4 cell line

Preparation Method

MRP4 was overexpressed in the HEK293/MRP4 cell line. The PU 23 compounds in the presence of 6-MP(15 μM), using MK571 as the positive control. Cell viability was assessed using sulforhodamine B (SRB)

Reaction Conditions

10 μM PU 23 for 72h.

Applications

PU 23 showed the highest activity with an inhibition rate of 81.71% at the concentration of 10 μM with 6-MP and only 15.26% without 6-MP. It increased cell sensitivity to 6-MP, but not toxic on its own.

PU 23 is a Multidrug resistance protein 4 (MRP4/ABCC4) inhibitor. MRP4 is an ATP-binding cassette (ABC) transporter. It is associated with multidrug resistance (MDR), which is becoming a growing challenge to the treatment of cancer and infections^[1].

Then compound PU 23 was discovered to improve HEK293/MRP4 cell sensibility to 6-MP dramatically, and low concentration PU 23 (5 μM) achieved the equivalent effect of 50 μM MK571. The accumulation of 6-MP was determined by validated high-performance liquid chromatography methods, and pretreatment of the HEK293/MRP4 cells with 50 μM MK571 or PU 23 resulted in significantly increased accumulation of 6-MP by approximately 1.5 times. This compound was first reported with a novel scaffold compared with previously known MRP4 inhibitors, which is a hopeful molecular tool that can be used for overcoming multidrug resistance research^[2].

References:
[1]: Chen Y, Yuan X, et al. Discovery of novel multidrug resistance protein 4 (MRP4) inhibitors as active agents reducing resistance to anticancer drug 6-Mercaptopurine (6-MP) by structure and ligand-based virtual screening. PLoS One. 2018 Oct 15;13(10):e0205175.