MK-571

MK-571 (L-660711) is an orally active, potent and selective competitive leukotriene D₄ (LTD₄) receptor antagonist, with K_i values of 0.22 and 2.1 nM in guinea pig and human lung membranes, respectively. MK-571 is also a MRP4 and ABCC1 (MRP1) inhibitor. MK-571 inhibits constitutive and antigen-stimulated S1P (sphingosine-1-phosphate) release^[1][2][3]. IC50 & Target:Ki: 0.22±0.15 nM (LTD₄, in guinea pig lung), 2.1±1.8 nM (LTD₄, in human lung)^[1]
pA2: 10.5 (LTD₄ on guinea pig ileum), 10.4 (LTE₄ on guinea pig ileum), 9.4 (LTD₄ on guinea pig trachea). 9.1 (LTE₄ on guinea pig trachea)^[1] In Vitro: MK571 (15 μM, 1 h) markedly suppresses constitutive and Ag-stimulated S1P secretion from RBL-2H3 cells and mast cells, and inhibits Fluo-3 efflux^[3]. In Vivo: MK-571 (0-0.5 mg/kg, orally, once) produces dose-dependent inhibition of the duration of antigen-induced dyspnea in conscious sensitized rats treated with methysergide (3 μg/kg)^[1].
MK-571 (0-1 mg/kg, orally, once) blocks LTD₄- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys^[1].
MK-571 (0-25 mg/kg, orally, daily, for 2 more weeks) shows reversal of hypoxic pulmonary hypertension (PH), and protects mice from hypoxic PH^[2].