LY255283

Names

[ Name ]:
LY255283

[Synonym ]:
1-(5-Ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)heptyloxy)phenyl)ethanone
1-(5-Ethyl-2-hydroxy-4-{[6-methyl-6-(2H-tetrazol-5-yl)heptyl]oxy}phenyl)ethanone
Ethanone, 1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(2H-tetrazol-5-yl)heptyl]oxy]phenyl]-

Biological Activity

[Description]:

LY255283 is a LTB4 receptor (BLT2) antagonist, with an IC50 of ~100 nM for [3H]LTB4 binding to guinea pig lung membranes[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Leukotriene Receptor

Research Areas >> Inflammation/Immunology

[Target]

LTB4:~100 nM (IC50, LTB4 binds to guinea pig lung membranes)

[In Vitro]

LY255283 compctitively reduces conlractilc responses of lung parcnchyma to LTB, (pA2 = 7.2)[2]. LY255283 (10 μM, 7 days) significantly suppresses the invasiveness of highly aggressive 253 J-BV bladder cancer cells[4]. Cell Viability Assay[4] Cell Line: 253 J-BV cells. Concentration: 5 or 10 μM. Incubation Time: 7 days. Result: Inhibition of BLT2 signaling attenuates aggressive migration by 253 J-BV cells.

[In Vivo]

LY255283 (3, 30 mg/kg) ameliorated lipopolysaccharide-induced ARDS in pigs, possibly by blocking the recruitment of activated PMNs into alveoli in a dose-dependent fashion[3]. LY255283 (2.5 mg/kg, ip) inhibits transitional cell carcinoma metastasis in mice models. The result suggests that a BLT2–Nox–ROS–NF–κB cascade plays a critical role in bladder cancer invasion and metastasis[4]. Animal Model: Mice (253 J-BV cells injected)[4]. Dosage: 2.5 mg/kg. Administration: IP injected 3 and 5 days after injection of cells. Result: By 12 weeks after injection, in mice treated with LY255283 only 0-3 nodules formed per lung, and histological analysis confirmed that the number of micrometastatic lesions was markedly reduced.

[References]

[1]. R M Schultz, et al. Effects of two leukotriene B4 (LTB4) receptor antagonists (LY255283 and SC-41930) on LTB4-induced human neutrophil adhesion and superoxide production. Prostaglandins Leukot Essent Fatty Acids. 1991 Aug;43(4):267-71.

[2]. S A Silbaugh, et al. Pulmonary actions of LY255283, a leukotriene B4 receptor antagonist. Eur J Pharmacol. 1992 Nov 13;223(1):57-64.

[3]. P S Wollert, et al. LY255283, a novel leukotriene B4 receptor antagonist, limits activation of neutrophils and prevents acute lung injury induced by endotoxin in pigs. Surgery. 1993 Aug;114(2):191-8.

[4]. Eun-Young Kim, et al. BLT2 promotes the invasion and metastasis of aggressive bladder cancer cells through a reactive oxygen species-linked pathway. Free Radic Biol Med. 2010 Sep 15;49(6):1072-81.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
573.4±60.0 °C at 760 mmHg

[ Melting Point ]:
160-162 °C

[ Molecular Formula ]:
C₁₉H₂₈N₄O₃

[ Molecular Weight ]:
360.451

[ Flash Point ]:
300.6±32.9 °C

[ Exact Mass ]:
360.216156

[ PSA ]:
100.99000

[ LogP ]:
4.04

[ Vapour Pressure ]:
0.0±1.6 mmHg at 25°C

[ Index of Refraction ]:
1.553

Safety Information

[ Hazard Codes ]:
F+

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2933990090

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Leukotriene B4 Inhibits L-Type Calcium Channels via p38 Signaling Pathway in Vascular Smooth Muscle Cells.

Cell Physiol. Biochem. 37 , 1903-13, (2015)

Arachidonic acid (AA) and its metabolites are important endogenous lipid messengers. In this study, we test the effect of Leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of AA, on L-type calcium ch...

12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor.

J. Exp. Med. 211(6) , 1063-78, (2014)

Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein-coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. Despite the well-defined proinflammatory roles...

A leukotriene B4 receptor-2 is associated with paclitaxel resistance in MCF-7/DOX breast cancer cells.

Br. J. Cancer 109(2) , 351-9, (2013)

Breast cancer is the most common malignancy in women. Although chemotherapeutic agents, such as paclitaxel, are effective treatments for the majority of breast cancer patients, recurrence is frequent ...