Etalocib (LY293111), an orally active leukotriene B4 receptor antagonist, inhibits the binding of [3H]LTB4, with a Ki of 25 nM. Etalocib (LY293111) prevents LTB4-induced calcium mobilization with an lC50 of 20 nM. Etalocib (LY293111) induces apoptosis[1][2][3].
体外研究 (In Vitro)
Etalocib (LY293111) elicits a concentration-dependent inhibition of LTB4 induced CD11b up-regulation[1]. Etalocib (LY293111) is an extremely potent and selective antagonist of human neutrophil function in vitro[2]. Etalocib (LY293111, 250 and 500 nM, 24-72 h) induces apoptosis and inhibits proliferation in human pancreatic cancer cells[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[3]
Cell Line:
MiaPaCa-2 and AsPC-1 human pancreatic cancer cells.[3]
Concentration:
500 nM.
Incubation Time:
24, 48, and 72 h.
Result:
Caused both a concentration-dependent and time-dependent inhibition of thymidine incorporation in both MiaPaCa-2 and AsPC-1 human pancreatic cancer cells.
Apoptosis Analysis[3]
Cell Line:
MiaPaCa-2 and AsPC-1 human pancreatic cancer cells.
Concentration:
250 and 500 nM.
Incubation Time:
24 h.
Result:
Induced apoptosis in human pancreatic cancer cells.
体内研究 (In Vivo)
Etalocib (LY293111) produces a dose-related inhibition of acute leukotriene B4-induced airway obstruction when administered i.v. (ED50=14 µg/kg) or p.o. (ED50=0.4 mg/kg)[2]. Etalocib (LY293111, 10 mg/kg) inhibits A23187-induced lung inflammatory changes at 1 h[2]. Etalocib (LY293111, 250 mg/kg/day, orally) inhibits growth of human pancreatic cancer xenografts in athymic mice[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Guinea pigs[2].
Dosage:
1-10 mg/kg.
Administration:
Orally once.
Result:
A single 1 mg/kg oral dose inhibited excised lung gas volume increases by 76.7±7.1% (n=4, P<0.002) when given 8 h prior to leukotriene B4 challenge, and 28.6±20.3% (n=4, NS) when given 24 h before challenge. Had no effect (10 mg/kg) on pulmonary gas trapping at 1 h or 2 h after A23187 challenge. However, at 4 h, the pulmonary gas trapping response was significantly less than that of vehicle-treated controls and not different from sham values. The 10 mg/kg dose inhibited A23187-induced lung inflammatory changes at 1 h, but was without effect at 2 h or 4 h after challenge.
Clinical Trial
分子量
544.61
Formula
C33H33FO6
CAS 号
161172-51-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. P Marder, et al. Blockade of Human Neutrophil Activation by 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5- Hydroxyphenoxy]propoxy]phenoxy]benzoic Acid (LY293111), a Novel Leukotriene B4 Receptor Antagonist. Biochem Pharmacol. 1995 May 26;49(11):1683-90.
[2]. S A Silbaugh, et al. Pharmacologic Actions of the Second Generation Leukotriene B4 Receptor Antagonist LY29311: In Vivo Pulmonary Studies. Naunyn Schmiedebergs Arch Pharmacol. 2000 Apr;361(4):397-404.
[3]. Wei-Gang Tong, et al. Leukotriene B4 Receptor Antagonist LY293111 Inhibits Proliferation and Induces Apoptosis in Human Pancreatic Cancer Cells. Clin Cancer Res. 2002 Oct;8(10):3232-42.
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].
IC50 & Target[2]
LTB4
~100 nM (IC50, LTB4 binds to guinea pig lung membranes)
体外研究 (In Vitro)
LY255283 competitively 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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
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.
体内研究 (In Vivo)
LY255283 (3, 30 mg/kg) ameliorates 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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
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.
分子量
360.45
Formula
C19H28N4O3
CAS 号
117690-79-6
运输条件
Room temperature in continental US; may vary elsewhere.
[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.
