Description
Pranlukast-d4 is intended for use as an internal standard for the quantification of pranlukast by GC- or LC-MS. Pranlukast is an orally bioavailable cysteinyl leukotriene 1 (CysLT1) receptor antagonist (IC50s = 4.3-7.2 nM in radioligand binding assays).1 It is selective for the CysLT1 receptor over the CysLT2 receptor (IC50 = 3,620 nM for the human receptor).2 Pranlukast inhibits mucus secretion induced by leukotriene D4 (LTD4; ） in isolated guinea pig trachea with an IC50 value of 0.3 μM.3 It inhibits TNF-α-induced NF-B p65 nuclear localization in U937 and Jurkat cells when used at concentrations of 10 and 100 μM.4 Pranlukast inhibits bronchoconstriction induced by LTC4 , LTD4, and LTE4 , but not LTB4 , in guinea pigs (ID50s = 0.8, 1, 0.7, and >500 μg/kg, respectively).5 It reduces cortical infarct volume by 81.6% and decreases neuronal death in the cortex, hippocampus, and striatum in a rat model of ischemia induced by middle cerebral artery occlusion (MCAO) when administered at a dose of 0.03 mg/kg.6
Uses
Pranlukast-d4 is deuterium labeled Pranlukast. Pranlukast is a highly potent, selective and competitive antagonist of peptide leukotrienes. Pranlukast inhibits [3H]LTE4, [3H]LTD4, and [3H]LTC4 bindings to lung membranes with Kis of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively.
References
1. Lynch, K.R., O'Neill, G.P., Liu, Q., et al. Characterization of the human cysteinyl leukotriene CysLT1 receptor Nature 399(6738),789-793(1999).
2. Heise, C.E., O'Dowd, B.F., Figueroa, D.J., et al. Characterization of the human cysteinyl leukotriene 2 receptor J. Biol. Chem. 275(39),30531-30536(2000).
3. Liu, Y.-C., Khawaja, A.M., and Rogers, D.F. Effects of the cysteinyl leukotriene receptor antagonists pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in vitro Br. J. Pharmacol. 124(3),563-571(1998).
4. Ichiyama, T., Hasegawa, S., Umeda, M., et al. Pranlukast inhibits NF-KB activation in human monocytes/macrophages and T cells Clin. Exp. Allergy 33(6),802-807(2003).
5. Nakai, H., Konno, M., Kosuge, S., et al. New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships J. Med. Chem. 31(1),84-91(1988).
6. Zhang, W.-P., Wei, E.-Q., Mei, R.-H., et al. Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia in rats Acta Pharmacol. Sin. 23(10),871-877(2002).
