Etalocib (LY293111), an orally active leukotriene B4 receptor antagonist, inhibits the binding of [3H]LTB4, with a Ki of 25 nM. LY293111 prevented LTB4-induced calcium mobilization with an IC50 = 20 nM, or 40 times more effectively than SC-41930 (IC50 = 808 nM). LY293111 was 300 times more potent than SC-41930 in blocking LTB4-induced CD11b up-regulation on isolated neutrophils. LY293111 also arrested LTB4-induced up-regulation of CD11b on neutrophils in whole human blood. LY293111 was not effective in blocking human neutrophil activation responses induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), platelet-activating factor (PAF), human recombinant endothelial interleukin-8 (IL-8) or human recombinant complement component 5a (C5a).[2]. LY293111 sodium produced a dose-related inhibition of acute leukotriene B4-induced airway obstruction when administered i.v. (ED50=14 microg/kg) or p.o. (ED50=0.4 mg/kg). In contrast, LY293111 sodium did not inhibit the pulmonary gas trapping caused by aerosols of histamine, leukotriene D4, or the thromboxane mimetic U46619. Oral LY293111 sodium inhibited leukotriene B4-induced bronchoalveolar lavage granulocyte infiltration and delayed onset airway obstruction at doses as low as 0.3 mg/kg. In A23187-challenged animals, pulmonary inflammation was markedly inhibited at 1 h, but not 2 h and 4 h post-exposure. LY293111 sodium is a selective leukotriene B4 receptor antagonist with potent pulmonary anti-inflammatory activity[3].The LTB4 receptor antagonist LY293111 caused both time- and concentration-dependent inhibition of proliferation of all six human pancreatic cancer cell lines studied. LY293111 induced apoptosis in these pancreatic cancer cell lines, as indicated by morphology, TUNEL assay, and poly(ADP-ribose) polymerase cleavage.Using AsPC-1 and HPAC cell xenografts in athymic mice, LY293111 treatment markedly inhibited tumor growth over a 24-day treatment period, as measured by both tumor volume and tumor weight. In situ tissue TUNEL assay showed massive apoptosis in LY293111-treated tumor tissues[4].
Etalocib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Vulvovaginal candidiasis model
Intraperitoneal injection
1 mg/kg
Once daily for 16 days
To evaluate the effect of Etalocib on vaginal PMN migration. Results showed that Etalocib did not significantly reduce vaginal PMN migration.
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