cyslt1

Gemilukast (ONO-6950) is an orally active and potent dual inhibitor of cysteinyl leukotriene 1 and 2 receptors (CysLT1 and CysLT2), inhibits LTC 4-induced bronchoconstriction, and is inhibitory to human CysLT1 and CysLT2, and may be used in the treatment of asthma.

LM-1484 displays a higher affinity for 3H-LTC4 sites and is an antagonist of CysLT1 receptor.

KP496 is a selective, dual antagonist for the Thromboxane A2 receptor (TP) and the Leukotriene D4 receptor (cysLT1).

CP-199331, a cysLT1 receptor antagonist, demonstrates equivalent potency to commercially available cysLT1 receptor antagonists zafirlukast and pranlukast. It shows favorable pharmacokinetic properties in both rats and monkeys, and unlike CP-85,958, no hepatotoxicity has been observed in monkeys.

BAY-u 9773 is a non-selective antagonist of cysteinyl leukotrienes receptors (CysLT receptors), with approximately equal IC50 values for both CysLT1 and CysLT2. BAY-u 9773 is used to inhibit leukotriene responses [1].

CysLT1 leukotriene receptor antagonist

Quininib is a selective antagonist of CysLTR1 and CysLTR2, with IC50 values of 1.2 and 52 μM, respectively, exhibiting anti-angiogenic and anti-tumour effects.

CP-199330 is a cysteyl LT1 receptor antagonist with no hepatotoxicity and is equivalent to the commercially available CYSLT1 receptor antagonists Zafirlukast and Pranlukas.

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.

Iralukast is a cysteinyl-leukotriene antagonist (CysLT) with a pKi of 7.8 for CysLT1.

Dihydro montelukast is a potential impurity found in commercial montelukast preparations. Montelukast (sodium salt) is a potent and selective cysteinyl leukotriene 1 (CysLT1) receptor antagonist. Formulations containing montelukast are used for the treatment of asthma as well as for the symptoms associated with allergic rhinitis.

Produced by neutrophils, macrophages, mast cells, and by transcellular metabolism in platelets, leukotriene C4 (LTC4) is the parent cysteinyl leukotriene formed by the LTC4 synthase-catalyzed conjugation of glutathione to LTA4. It is one of the constituents of slow-reacting substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle contracting activity. LTC4, however, is rapidly metabolized to LTD4 and LTE4, which makes the characterization of LTC4 pharmacology difficult. N-methyl Leukotriene C4 (N-methyl LTC4) is a synthetic analog of LTC4 that is not readily metabolized to LTD4 and LTE4.It acts as a potent and selective CysLT2 receptor agonist exhibiting EC50 values of 122 and > 2,000 nM at the human CysLT2 and CysLT1 receptors, respectively. It has essentially the same potency as LTC4 at both the human and murine receptors CysLT2 receptors. N-methyl LTC4 is potent and active in vivo, causing vascular leak in mice overexpressing the human CysLT2 receptor but not in CysLT2 receptor knockout mice.

CAY10789 (compound 6) is a potent CysLT1R (cysteinyl leukotriene receptor 1) antagonist with an IC50 of 2.80 μM and a GPBAR1 (G-protein-coupled bile acid receptor 1) agonist with an EC50 of 3 μM. It significantly decreases U937 cell adhesion to HAEC and reduces TNF-α expression. CAY10789 demonstrates promising metabolic stability and excellent pharmacokinetics, making it suitable for studying colitis, metabolic syndromes, and other GPBAR1/CysLT1R-related diseases [1].

ONO-4310321 is a potent, orally available dual CysLT1 and CysLT2 receptor antagonist.

FPL-55712 is a CysLT1 leukotriene receptor antagonist.

ONO-2050297 is the first potent dual CysLT1 and CysLT2 antagonist with IC50 values of 0.017 μM (CysLT1) and 0.00087 μM (CysLT2), respectively.

CAY10788 is an antagonist of CysLT1 receptor.

Montelukast dicyclohexylamine (MK0476), a potent, selective, and orally active antagonist of the cysteinyl leukotriene receptor 1 (CysLT1), is utilized in the research of asthma, liver injury, and COVID-19. It exhibits antioxidant properties in the context of intestinal ischemia-reperfusion injury and can mitigate cardiac damage. Additionally, it reduces eosinophil infiltration in the airways of asthmatic patients.

MK 571 (L660711) is an orally active antagonist of CysLT1 receptor.

S-Geranylgeranyl-L-glutathione acts as a ligand for the orphan G protein-coupled receptor (GPCR) P2RY8, displaying selective affinity by inducing internalization of P2RY8 in preference to the sphingosine-1-phosphate receptor 2 (S1P2), GPR55, cysteinyl leukotriene receptor 1 (CysLT1 receptor), and the CysLT2 receptor at a concentration of 100 nM. Additionally, at a lower concentration of 10 nM, S-Geranylgeranyl-L-glutathione inhibits the chemokine (C-X-C motif) ligand 12-induced migration of both P2RY8-expressing WEHI-231 B cell lymphoma cells and human tonsil germinal center B cells.