BLT1 Leukotriene Receptor Antibodies

BLT1, also known as leukotriene B4 receptor 1 (LTB4R), is a class A GPCR and the high-affinity receptor for the lipid mediator leukotriene B4 (LTB4). BLT1 predominantly couples to Gi/o and Gq/11 proteins, resulting in inhibition of adenylyl cyclase, activation of phospholipase C, intracellular Ca2+ mobilization and MAPK signaling. The receptor is expressed mainly in leukocytes, including neutrophils, monocytes, macrophages, eosinophils, dendritic cells and subsets of B and T lymphocytes, but is also present in vascular and bronchial smooth muscle and endothelial cells. LTB4 activation of BLT1 is a potent stimulus for leukocyte chemotaxis, adhesion, activation and degranulation and therefore plays a central role in innate immune responses. Excessive LTB4–BLT1 signaling contributes to chronic inflammatory and autoimmune diseases, including asthma, rheumatoid arthritis, psoriasis, inflammatory bowel disease and atherosclerosis. Several potent selective BLT1 antagonists have been developed, including CP-105,696, BIIL-260, LY293111, ONO-4057 and U-75302, which have shown anti-inflammatory activity in numerous preclinical models. Despite extensive drug-development efforts, no selective BLT1 antagonist has so far been approved as a therapeutic drug. The most advanced compounds have generally failed to demonstrate sufficient clinical efficacy or suitable pharmacological profiles, and BLT1 therefore remains a clinically unvalidated but pharmacologically well-characterized target. Overall, BLT1 represents an attractive target for modulation of pathological leukocyte recruitment and inflammation, particularly in diseases in which excessive neutrophil and macrophage activation plays a central role. For more information on BLT1 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.