CysLT1 Cysteinyl-Leukotriene Receptor 1 Antibodies

CYSLT1, also known as the cysteinyl leukotriene receptor 1 (CysLT1), is a class A GPCR that mediates the actions of the cysteinyl leukotrienes LTC4, LTD4 and LTE4, with LTD4 generally being the most potent endogenous agonist. The receptor predominantly couples to Gq/11 proteins, activating phospholipase C, increasing intracellular Ca2+ and stimulating downstream MAPK signaling, although Gi/o-dependent signaling has also been described. CYSLT1 is expressed in airway and vascular smooth muscle cells as well as in numerous inflammatory and immune cells, including eosinophils, mast cells, monocytes, macrophages, neutrophils and subsets of T and B lymphocytes. Activation of CYSLT1 induces bronchoconstriction, increased vascular permeability, mucus secretion and inflammatory-cell activation, making it a major mediator of allergic airway inflammation. The receptor therefore plays an important role in the pathophysiology of asthma and allergic rhinitis and is also implicated in other inflammatory diseases. CYSLT1 is one of the best pharmacologically validated GPCR targets in respiratory medicine. Several potent selective antagonists have been developed, most importantly montelukast, zafirlukast and pranlukast, which block the effects of cysteinyl leukotrienes at CYSLT1. Montelukast and zafirlukast are approved drugs used particularly for the treatment and prevention of asthma and for allergic rhinitis, while pranlukast is approved in several countries, particularly in Asia. Despite the availability of effective CYSLT1 antagonists, these drugs are generally used as adjunctive rather than first-line therapy for asthma, and their clinical efficacy varies between patients. Overall, CYSLT1 represents a highly validated inflammatory GPCR and an established therapeutic target, particularly for asthma and other leukotriene-driven respiratory diseases. For more information on CYSLT1 pharmacology please refer to the IUPHAR database. For further reading refer to:

Bäck M, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE. International Union of Basic and Clinical Pharmacology. LXXXIV: leukotriene receptor nomenclature, distribution, and pathophysiological functions. Pharmacol Rev. 2011 Sep;63(3):539-84. doi: 10.1124/pr.110.004184. PMID: 21771892.

Bäck M, Powell WS, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE. Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7. Br J Pharmacol. 2014 Aug;171(15):3551-74. doi: 10.1111/bph.12665. Epub 2014 Jul 12. PMID: 24588652; PMCID: PMC4128057.