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Zileuton

別名: A-64077 中文名稱：齊留通

Zileuton是一種口服有效的5-脂氧合酶5-lipoxygenase抑制劑，從而抑制白三烯（LTB 4，LTC 4，LTD 4和LTE 4）的形成，用來(lái)緩解哮喘的癥狀。Zileuton 可誘導(dǎo)凋亡而抑制鐵死亡。

Zileuton Chemical Structure

Zileuton Chemical Structure

CAS: 111406-87-2

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買(mǎi)數(shù)量
10mM (1mL in DMSO) 1061.95 現(xiàn)貨
20mg 810.23 現(xiàn)貨
1g 7944.3 現(xiàn)貨
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Zileuton相關(guān)產(chǎn)品

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
RAW264.7 Function assay 5 uM 24 hrs Inhibition of LPS/IFNgamma-stimulated lipid peroxidation in mouse RAW264.7 cells at 5 uM after 24 hrs by BODIPY 581/591 C11-staining based FACS assay 30964295
RAW264.7 Function assay 5 uM 48 hrs Protection against LPS-induced cell death in mouse RAW264.7 cells assessed as increase in cell viability at 5 uM measured after 48 hrs by MTS assay relative to control 30964295
HEK293 Function assay 1 uM 5 mins Inhibition of human 5-LO transfected in HEK293 cells coexpressing FLAP assessed as reduction in leukotriene formation at 1 uM using arachidonic acid as substrate preincubated for 5 mins followed by calcium ionophore A23187/arachidonic acid addition and me 31260889
PMNL Function assay 1 uM 5 mins Inhibition of 5-LO in human PMNL cells assessed as reduction in leukotriene formation at 1 uM preincubated for 5 mins followed by thapsigargin stimulation measured after 15 mins by RP-HPLC analysis relative to control 31260889
PMNL Function assay 15 mins Inhibition of 5-lipoxygenase in cell free S100 freshly isolated human PMNL cells assessed as inhibition of A23187-stimulated 5-LO product formation preincubated for 15 mins measured after 10 mins by HPLC analysis, IC50=0.5μM 22551629
BMM Function assay 30 mins Inhibition of 5-LO in mouse BMM cells assessed as formation of LTC4 after 30 mins by enzyme immunoassay, IC50=0.19μM 26432605
A549 Function assay 15 mins Inhibition of mPGES-1 isolated from microsomes of interleukin-1 beta-stimulated human A549 cells using PGH2 as substrate preincubated for 15 mins followed by substrate addition measured after 1 min by RP-HPLC analysis, IC50=0.6μM 30053720
PMNL Function assay 5 mins Inhibition of 5-LO in human PMNL cells assessed as reduction in leukotriene formation preincubated for 5 mins followed by thapsigargin stimulation measured after 15 mins by RP-HPLC analysis, IC50=2.31μM 31260889
BL21 (DE3) Function assay 10 mins Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 (DE3) cells using arachidonic acid as substrate preincubated for 10 mins followed by susbtrate addition and measured after 10 mins by reverse phase HPLC method, IC50=0.5μM 31465225
insect cells Function assay 5 mins Inhibition of human recombinant 5-LOX expressed in insect cells assessed as decrease in production of 5-HPETE and 5-HETE using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition measured after 20 mins in dark by ferric io, IC50=23.9μM 31774676
Sf21 Function assay 4 mins Inhibition of rat 5-LOX expressed in Sf21 insect cells preincubated for 4 mins followed by AA substrate addition and measured after 4 mins by FOX assay, IC50=0.18μM ChEMBL
RBI-1 Function assay In vitro inhibition of 5-lipoxygenase (5-lo) from the 20000 g supernatant of RBI-1 cells, IC50=0.6μM 2066989
RBL-1 Function assay Inhibitory concentration against 5-lipoxygenase in rat RBL-1 cells, IC50=3.2μM 8831759
basophilic leukemia cells Function assay Inhibitory activity against 5-lipoxygenase obtained from rat basophilic leukemia cells, IC50=0.5μM 9484493
RBL-2H3 Function assay Inhibition of 5-lipoxygenase mediated conversion of [14C]arachidonic acid to leukotrienes in RBL-2H3 cells, IC50=0.804μM 9599246
granulocytes-type cells Function assay The compound was evaluated for its inhibitory activity against 5-lipoxygenase using granulocytes-type cells, IC50=2.9μM 11859001
polymorphonuclear cells Antileukotrienic assay Antileukotrienic activity in rat polymorphonuclear cells assessed as inhibition of LTB4 biosynthesis, IC50=0.01μM 17448575
MC9 Function assay Inhibition of LTB4 production in mouse MC9 cells, IC50=0.55μM 18498150
MC9 Function assay Inhibition of leukotrienes production in mouse MC9 cells 18498150
RBL-2H3 Function assay Inhibition of 5-Lipoxygenase of rat basophilic leukemia cells, IC50=0.14μM ChEMBL
RBL-2H3 Function assay In vitro inhibition of 5-lipoxygenase in RBL-2H3 (Rat basophilic leukemia) cells, IC50=1.25μM ChEMBL
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生物活性

產(chǎn)品描述 Zileuton是一種口服有效的5-脂氧合酶5-lipoxygenase抑制劑，從而抑制白三烯（LTB 4，LTC 4，LTD 4和LTE 4）的形成，用來(lái)緩解哮喘的癥狀。Zileuton 可誘導(dǎo)凋亡而抑制鐵死亡。
靶點(diǎn)
Ferroptosis [6] 5-lipoxygenase [1]
體外研究(In Vitro)
體外研究活性

在巨噬細(xì)胞中，Zileuton過(guò)干擾花生四烯酸（AA）的釋放來(lái)抑制PG生物合成。在活化的小鼠腹腔巨噬細(xì)胞和巨噬細(xì)胞J774中，Zileuton顯著降低PGE2和6酮前列腺素F1α（PGF1α）水平。在LPS刺激的人全血中，Zileuton抑制PGE2產(chǎn)生與抑制PGE2。在大鼠角叉菜膠誘導(dǎo)的胸膜炎中，Zileuton抑制PGE2和6-酮前列腺素F1α胸膜水平。[1]
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

在大鼠中，Zileuton治療4周后顯著降低宏觀損傷評(píng)分。在大鼠結(jié)腸內(nèi)，Zileuton顯著增加血栓素B2在1周的釋放和前列腺素E2在周2和4的釋放。[2] 在小鼠中，Zileuton減小脊髓炎癥和組織損傷，中性粒細(xì)胞浸潤(rùn)，腫瘤壞死因子-α，COX-2和磷酸化ERK1/2的表達(dá)，前列腺素E（2）和LTB（4）的生產(chǎn)。在小鼠中，Zileuton顯著改善肢體功能的恢復(fù)10天。[3] 在5脂氧合酶基因敲除小鼠中，Zileuton在I/R之前給藥顯著降低腎功能不全（尿素，肌酐）和損傷（AST，組織學(xué)）的程度。在5脂氧合酶基因敲除小鼠的腎中，Zileuton降低ICAM-1的表達(dá)和I/R的相關(guān)聯(lián)的中性粒細(xì)胞浸潤(rùn)。[4] 在Zileuton和JNJ-26993135處理的小鼠中，Zileuton更有效地抑制白三烯B（4）的產(chǎn)生，和嗜中性粒細(xì)胞的流入。[5]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01136941 Completed
Sickle Cell Disease
Children''s Hospital Medical Center Cincinnati
 September 2010 Phase 1
NCT01130688 Terminated
Chronic Myelogenous Leukemia
University of Massachusetts Worcester
 January 2010 Phase 1

化學(xué)信息&溶解度

分子量 236.29 分子式

C11H12N2O2S
CAS號(hào) 111406-87-2 SDF Download Zileuton SDF
Smiles CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 47 mg/mL ( (198.9 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Ethanol : 47 mg/mL (198.9 mM)

Water : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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