MK-571 sodium (L-660711 sodium salt) is a selective, orally active antagonist of the CysLT1 receptor. MK-571 sodium is a multidrug resistance protein-2 (ABCC2, Mrp2) inhibitor used to demonstrate the role of Mrp2 in the cellular efflux of drugs, xenobiotics, and their conjugates. MK-571 sodium can inhibit the synthesis of K-4′-O-GlcA (19.7 μM). MK571 dose-dependently inhibits the intracellular biosynthesis of all flavonol sulphates and glucuronides by Caco-2 cells. MK-571 sodium significantly inhibits phase-2 conjugation of kaempferol by cell-free extracts of Caco-2, and production of kaempferol-4′-O-glucuronide was competitively inhibited. In addition to inhibiting MRP2, MK571 is a potent inhibitor of enterocyte phase-2 conjugation.

LTD4:0.22 nM (Ki, In guinea pig lung), LTD4:2.1 nM (Ki, In human lung)

In human lungs, MK-571 inhibited [3H]LTD4 binding (Ki: 2.1±1.8 nM, n=29), whereas in guinea pig lungs the Ki value was 0.22±0.15 nM (n=35). However, its binding activity to [3H]LTC4 was low or absent (IC50: 32 μM, n=1, human; 23±11 μM, n=16, guinea pig).

In human lungs, MK-571 inhibited [3H]LTD4 binding (Ki: 2.1±1.8 nM, n=29), whereas in guinea pig lungs the Ki value was 0.22±0.15 nM (n=35). However, its binding activity to [3H]LTC4 was low or absent (IC50: 32 μM, n=1, human; 23±11 μM, n=16, guinea pig).

Cells were seeded onto 96 well plates at a concentration of 1×103 cells per well and incubated for 72 h at 37?C and 5% CO2 to allow MRP1 messenger RNA suppression to occur. Cells were then treated with either control media or one of three chemotherapy drugs temozolomide (150 µM), vincristine (100 nM), or etoposide (2 µM). Cells were then returned to the incubator for a further 72 h; after which time, Metylthiazol Tetrazolium (MTT) powder in PBS (50µl of 5 mg/ml) was added to each well. Cells were then incubated for a further 4 h after which all solution was removed and dimethyl sulfoxide (DMSO) was added. After 10 min incubation time at 37?C, absorbance was recorded at 570 nm wavelength and data was recorded and analyzed. Small molecule inhibitors MK571 (25 µM) and Reversan (15µM) were added 7 h prior to carrying out further drug treatment (temozolomide, vincristine or etoposide) or assay assessment (media change for proliferation and 2D-migration assays) (Only for Reference)