ML352_突触前胆碱转运体抑制剂_1649450-12-3_Apexbio

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DIDS_阴离子运输抑制剂_67483-13-0_Apexbio

Limited solubility
Store at +4°C
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
实验操作
细胞实验: 细胞系溶解方法
反应时间应用
来源于 6-8 周龄 Sprague-Dawley 大鼠的 DRG（背根神经节）神经元细胞
在 DMSO 中的溶解度>10mM。为了获得更高的浓度，可以将离心管在 37℃加热 10 分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月
0.1, 1, 3, 10, 100μm 作用 2min，加入第一滴药物开始同时观察
在 DGR 神经元中，尽管 DIDS 并没有诱导 TRPV1（瞬时受体电位香草酸亚型 1 型）自身的活化，但是显著提高了辣椒素或低 pH 诱导的 TRPV1 电流。DIDS 可以以激动剂依赖的方式改变 TRPV1 通道功能。
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。
参考文献: [1] Wulff, Heike. "New light on the “Old” chloride channel blocker DIDS." ACS chemical biology 3.7 (2008): 399-401. [2] Hogg, R. C., Q. Wang, and W. A. Large. "Effects of Cl channel blockers on Ca‐activated chloride and potassium currents in smooth muscle cells from rabbit portal vein." British journal of pharmacology 111.4 (1994): 1333-1341. [3] Nelson, Mark T., et al. "Chloride channel blockers inhibit myogenic tone in rat cerebral arteries." The Journal of Physiology 502.2 (1997): 259-264. [4] Lyons, John C., Brian D. Ross, and Chang W. Song. "Enhancement of hyperthermia effect in vivo by amiloride and DIDS." International Journal of Radiation Oncology* Biology* Physics 25.1 (1993): 95-103

Mexiletine HCl_钠通道抑制剂_5370-01-4_Apexbio

Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request
生物活性
靶点 : 信号通路: 产品描述:
Mexiletine HCl belongs to Class IB anti-arrhythmic group of medicines, inhibits sodium channels to reduce the inward sodium current. 参考文献:
产品说明书
化学性质产品名Biblioteka Cas No.: 分子量: 分子式:
Mexiletine HCl 5370-01-4 215.72 C11H17NO.HCl
产品名: Mexiletine HCl 修订日期: 6/30/2016
化学名: SMILES: 溶解性: 储存条件: 一般建议:
运输条件:
1-(2,6-dimethylphenoxy)propan-2-amine;hydrochloride
ApexBio Technology
特别声明
产品仅用于研究，不针对患者销售，望谅解。每个产品具体的储存和使用信息显示在产品说明书中。ApexBio 产品在推荐的条件下是稳定的。产品会根据不同的推荐温度进行运输。许多产品短期运输是稳定的，运输温度不同于长期储存的温度。我们确保我们的产品是在保持试剂质量的条件下运输的。收到产品后，按照产品说明书上的要求进行储存。
CC1=C(C(=CC=C1)C)OCC(C)N.Cl
>10.2mg/mL in DMSO
Store at -20°C

依达拉奉右莰醇通过抑制TLR4NF-κB信号通路减轻实验性自身免疫性脑脊髓炎小鼠炎症反应

实验研究依达拉奉右莰醇通过抑制TLR4/NF-κB信号通路减轻实验性自身免疫性脑脊髓炎小鼠炎症反应晚丽，李作孝△摘要：目的探讨依达拉奉右莰醇对实验性自身免疫性脑脊髓炎（EAE）小鼠炎症反应的影响及其机制。

方法30只雌性C57BL/6小鼠随机分为空白组、模型组、依达拉奉右莰醇干预组各10只。

除空白组外，其余2组小鼠均采用髓鞘少突胶质细胞糖蛋白35-55（MOG35-55）多肽诱导EAE模型。

从造模次日开始，依达拉奉右莰醇干预组腹腔注射依达拉奉右莰醇12.5mg/kg，空白组及模型组腹腔注射等量生理盐水，1次/d，连续14d。

观察小鼠发病情况，并行神经功能障碍评分；HE和LFB染色观察脊髓组织病理改变；实时荧光定量PCR检测脑组织匀浆中白细胞介素（IL）-1β、IL-6及肿瘤坏死因子（TNF）-αmRNA表达水平；蛋白免疫印迹法检测脊髓组织中Toll样受体4（TLR4）、核因子κB p65（NF-κB p65）蛋白表达水平。

结果空白组小鼠均未发病，其余2组小鼠不同程度发病。

与模型组相比，依达拉奉右莰醇干预组小鼠的发病潜伏期、高峰期延迟，高峰期神经功能障碍评分降低（P＜0.01）。

空白组小鼠脊髓组织未见异常；模型组脊髓组织大量炎性细胞浸润、髓鞘结构紊乱；依达拉奉右莰醇干预组较模型组的炎性细胞浸润减少、髓鞘结构紊乱情况改善。

与空白组相比，其余2组小鼠脑组织匀浆中IL-1β、IL-6、TNF-αmRNA表达水平以及脊髓组织中TLR4、NF-κB p65蛋白表达水平显著升高，以依达拉奉右莰醇干预可逆转建模引起的上述改变（P＜0.05）。

结论依达拉奉右莰醇可减轻EAE小鼠炎症反应，其机制可能与抑制TLR4/NF-κB信号通路活化有关。

关键词：脑脊髓炎，自身免疫性，实验性；Toll样受体4；NF-κB；炎症；白细胞介素类；肿瘤坏死因子α；依达拉奉右莰醇；TLR4/NF-κB信号通路中图分类号：R744.51文献标志码：A DOI：10.11958/20212362Edaravone dexborneol reduces inflammation in mice with experimental autoimmuneencephalomyelitis by inhibiting TLR4/NF-κB signaling pathwayWAN Li,LI Zuoxiao△Department of Neurology,the Affiliated Hospital of Southwest Medical University,Luzhou646000,China△Corresponding Author E-mail:****************Abstract:Objective To investigate the effect and mechanism of edaravone dexborneol on the inflammatory response in mice with experimental autoimmune encephalomyelitis(EAE).Methods Thirty female C57BL/6mice were randomly divided into the blank group,the model group and the edaravone dexborneol intervention group,with10mice in each group. Except for the blank group,EAE model was induced by myelin oligodendrocyte glycoprotein35-55(MOG35-55) polypeptide in the other two groups.From the day after modeling,mice in the edaravone dexborneol intervention group were intraperitoneally injected with edaravone dexborneol12.5mg/kg,while the mice in the blank group and the model group were intraperitoneally injected with the equal amount normal saline,once a day for consecutive14days.The behavioral changes of mice were observed,and neurological dysfunction scores were performed.HE and LFB staining were used to detect spinal cord pathological changes.The mRNA expression levels of interleukin(IL)-1β,IL-6and tumor necrosis factor-α(TNF-α)in brain homogenate were detected by real-time fluorescence quantitative PCR.The protein expression levels of Toll-like receptor4(TLR4)and nuclear factorκB p65(NF-κB p65)in spinal cord tissue were detected by Western blot assay.Results None of the mice in the blank group had the disease,and the other two groups of mice had different degrees of pared with the model group,the incubation period and peak period were delayed in the edaravone dexborneol intervention group,and neurological deficit scores in peak period decreased(P＜0.01).No abnormality was found in spinal cord tissue structure in mice of the blank group,and a large number of inflammatory cell infiltration,myelin structure 基金项目：泸州市人民政府-西南医科大学科技战略合作基金项目（2018LZXNYD-ZK17）作者单位：西南医科大学附属医院神经内科（邮编646000）作者简介：晚丽（1994），女，硕士在读，主要从事神经免疫方面研究。

GTS 21 dihydrochloride_烟碱型乙酰胆碱受体(nAChRs)激动剂_156223-05-1_Apexbio

产品说明书
化学性质
产品名: Cas No.: 分子量: 分子式:
GTS 21 dihydrochloride 156223-05-1 381.3 C19H20N2O2.2HCl
产品名: GTS 21 dihydrochloride 修订日期: 6/30/2016
化学名: SMILESdihydrochloride 是一种新型的烟碱型乙酰胆碱受体（nAChRs）激动剂[1]。 nAChRs 是神经元受体蛋白，被神经递质乙酰胆碱（ACh）的结合所激活。在暴露于高氧（≥99％ O2）的 RAW 264.7 细胞（巨噬细胞样细胞系）中，GTS-21 以剂量依赖的方式显著增加巨噬细胞的吞噬活性，减少高氧诱导的 HMGB1 超乙酰化。GTS-21 也抑制 HMGB1 的细胞质易位以及从巨噬细胞中的释放[1]。GTS-21 与人α4β2 nAChR 结合的效力（Ki
Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request
靶点 :
Neuroscience
信号通路:
Nicotinic Receptor
参考文献: [1]. Sitapara RA, Antoine DJ, Sharma L, et al. The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function. Mol Med, 2014, 20: 238-247. [2]. Briggs CA, Anderson DJ, Brioni JD, et al. Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo. Pharmacol Biochem Behav, 1997, 57(1-2): 231-241.

Milnacipran_5-羟色胺-去甲肾上腺素再摄取抑制剂(SNRI)_92623-85-3_Apexbio

产品说明书
化学性质
产品名: Cas No.: 分子量: 分子式:
Milnacipran 92623-85-3 246.35 C15H22N2O
产品名: Milnacipran 修订日期: 6/30/2016
化学名:
SMILES: 溶解性: 储存条件: 一般建议:
运输条件:
(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carbo xamide
CCN(CC)C(=O)C1(CC1CN)C2=CC=CC=C2
Soluble in DMSO
Store at -20°C
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
ApexBio Technology
参考文献:
特别声明
产品仅用于研究，不针对患者销售，望谅解。每个产品具体的储存和使用信息显示在产品说明书中。ApexBio 产品在推荐的条件下是稳定的。产品会根据不同的推荐温度进行运输。许多产品短期运输是稳定的，运输温度不同于长期储存的温度。我们确保我们的产品是在保持试剂质量的条件下运输的。收到产品后，按照产品说明书上的要求进行储存。
Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request

Derquantel_烟碱乙酰胆碱受体拮抗剂_187865-22-1_Apexbio

产品名: Derquantel 修订日期: 6/30/2016产品说明书化学性质产品名:Derquantel //struct// Cas No.:187865-22-1 分子量:479.6 分子式:C28H37N3O4 别名: PF-00520904,PNU141962,2-deoxy-Paraherquamide化学名: (1'R,5'aS,7'R,8'aS,9'aR)-2',3',8'a,9,9',10-hexahydro-1'-hydroxy-1',4,4,8',8',11'-hexamethyl-spiro[4H,8H-[1,4]dioxepino[2,3-g]indole-8,7'(8'H)-[5H,6H-5a,9a](iminomethano)[1H]cyclopent[f]indolizin]-10'-oneSMILES: CC(C=CO1)(C)OC2=C1C(NC3)=C(C=C2)[C@]3(C4(C)C)C[C@]5(N(C)C6=O)[C@@]4([H])C[C@]6([C@](C)(O)CC7)N7C5溶解性: Soluble in DMSO储存条件: Store at -20°C一般建议: For obtaining a higher solubility , please warm the tube at 37°Cand shake it in the ultrasonic bath for a while.Stock solution can bestored below -20°C for several months.运输条件:Evaluation sample solution : ship with blue iceAll other available size: ship with RT , or blue ice upon request生物活性靶点 :Neuroscience 信号通路:Nicotinic Receptor 产品描述:Derquantel is a nicotinic acetylcholine receptor antagonist.Nicotinic acetylcholine receptors are receptor proteins that respond to the neurotransmitter acetylcholine. They are widely expressed in the central nervous system of humans, playing important roles in the peripheral nervous system.In vitro: A previous study investigated the effects of derquantel, abamectin and their combination on somatic muscle nicotinic acetylcholine receptors and pharyngeal muscle glutamate gated chloride receptor channels of Ascaris suum. Results showed that in combination, inhibition of the higher acetylcholine concentration response was greater than the predicted additive effect. Moreover, derquantel produced a potent reversible antagonism of acetylcholine depolarizations on somatic muscle. In addition, the effect of the combination was found to be significantly greater than the predicted additive effect of both drugs at higher acetylcholine concentrations [1].In vivo: Derquantel in combination with abamectin is a new approach for the treatment and control of parasites in sheep. 19 studies demonstrated the efficacy of derquantel-abamectin against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, which supported its registration. Another 11 studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance [2].Clinical trial: So far, no clinical study has been conducted.参考文献:产品仅用于研究，不针对患者销售，望谅解。

AG 555_EGFR激酶抑制剂_133550-34-2_Apexbio

O=C(/C(C#N)=C/C(C=C1O)=CC=C1O)NCCCC2=CC=CC=C2
Soluble in DMSO > 10 mM
Desiccate at +4°C
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
ApexBio Technology
参考文献: [1]. Ben-Bassat H, Rosenbaum-Mitrani S, Hartzstark Z, et al. Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent kinase 2 activation induce growth arrest, differentiation, and apoptosis of human papilloma virus 16-immortalized human keratinocytes. Cancer Res, 1997, 57(17): 3741-3750. [2]. Kleinberger-Doron N, Shelah N, Capone R, et al. Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase. Exp Cell Res, 1998, 241(2): 340-351. [3]. Sion-Vardy N, Vardy D, Rodeck U, et al. Antiproliferative effects of tyrosine kinase inhibitors (tyrphostins) on human bladder and renal carcinoma cells. J Surg Res, 1995, 59(6): 675-680. [4]. Seri I, Aflalo E, Gazit A, et al. Tyrphostin AG-555 inhibits early and late stages of Moloney murine leukemia virus replication cycle. Int J Oncol, 1997, 10(6): 1185-1189.

药理学胆碱受体阻断药

二、非去极化型肌松药又称竞争型肌松药（competive muscular relaxants）1：小剂量时，
竞争性阻断Ach对N2胆碱受体的兴奋，减少离子通道开放频率。2：大剂量时，药物也可进入突触前膜钠离子通道内，直接妨碍通道内离子转运，干扰神经末梢Ach的流动性，干扰Ach释放，有助于进一步抑制神经肌肉兴奋传递。本类药物的阻断作用可被胆碱酯酶抑制剂所拮抗。筒箭毒碱d-tubocurarine [药动学]：口服难吸收，静注后2min即显效，3-4min达分。大部分以原形从肾排出，仅有一小部分在体内代谢。其药理作用维持2040min。作用的消失主要由于药物在体内重分布，故重复用药要注意剂量，防止
• Nbl2o胆ck碱ing受dr体ug阻s）断药（N-cholinoceptor
能阻断节后胆碱能神经支配的效应器细胞上的M胆碱受体，发挥抗M样作用，表现出与毛果芸香碱相反的作用。本类药物均为竞争性拮抗剂，典型的药物是atropine。
又称神经节阻断剂，选择性的阻断神经节细胞上的N1胆碱受体。代表药：六甲双铵，美加明。
反应不良：常见有口干、心率加快、视力模糊、皮肤干燥、小便困难、心悸等。
酸中毒是影响机体对阿托品的敏感性与耐受性的重要因素，在酸中毒未纠正前，病人可耐受极大剂量的阿托品，同时不易显效。
阿托品中毒除上述外周症状加重外，中枢兴奋现象严重，呼吸加快加深，烦躁不安，谵妄，幻觉及惊厥等。
严重中毒可由兴奋转入抑制导致昏迷，后因呼吸麻痹而死亡。青光眼及前列腺肥大患者禁用。
剂量阿托品基本不影响动脉血压。大剂量阿托品用于感染性休克病人的治疗，能解除微血管痉挛,增加组织的有效灌注,改善微循环, 缓减休克症状。这种作用可能与阿托品在细胞水平的作用有关，而并非是直接作用于血管所致。 5中枢神经系统 : 治疗量对中枢神经系统作用不明显，较大剂量（1-2mg)可兴奋延脑呼吸中枢；高大剂量（2-5mg)则能兴奋大脑，出现烦躁不安、多言、瞻望等反应；

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特别声明
产品仅用于研究，
不针对患者销售，望谅解。
每个产品具体的储存和使用信息显示在产品说明书中。ApexBio 产品在推荐的条件下是稳定的。产品会根据不同的推荐温度进行运输。许多产品短期运输是稳定的，运输温度不同于长期储存的温度。我们确保我们的产品是在保持试剂质量的条件下运输的。收到产品后，按照产品说明书上的要求进行储存。
Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request
生物活性
靶点 :
Neuroscience
信号通路:
AChR
产品描述:
神经递质乙酰胆碱(ACh)在自主功能\运动控制\注意力\学习与记忆以及奖励中起着关键作用.高亲和力的胆碱转运体(CHT)是乙酰胆碱合成的限速因素,但 CHT 在突触胆碱信号检测与调控方面的应用仍有待开发.ML352 是新型的非竞争性突触前胆碱转运体抑制剂. 体外:在转染细胞与神经末梢制备物中,ML352 在完全拮抗 CHT 的浓度下对乙酰胆碱酯酶或胆碱乙酰转移酶无抑制作用,也缺乏对多巴胺\血清素\去甲肾上腺素转运体\多种受体以及离子
产品说明书
化学性质
产品名: Cas No.: 分子量: 分子式:
ML352 1649450-12-3 387.47 C21H29N3O4
产品名: ML352 修ILES: 溶解性: 储存条件: 一般建议:
运输条件:
(Z)-N-((3-isopropylisoxazol-5-yl)methyl)-4-methoxy-3-((1-methylpipe ridin-4-yl)oxy)benzimidic acid
CC(C1=NOC(C/N=C(O)/C2=CC(OC(CC3)CCN3C)=C(OC)C=C2)=C1)C
Soluble in DMSO
Store at -20°C
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
通道的活性.ML352 呈非竞争性地抑制完整细胞摄取胆碱并减少膜试验中密胆碱 3 结合位点的表观密度,这提示 ML352 与转运体之间的变构相互作用[1]. 体内:DMPK 实验表明,ML352 具有较高的静脉血浆清除率.此外,药物口服生物利用度以及脑内总浓度表明,ML352 有望作为一种合适的探针,用于研究啮齿动物体内可变的乙酰胆碱信号以及行为学效应[2]. 临床试验:到目前为止,ML352 还处于临床前开发阶段.
ApexBio Technology
参考文献: [1] Ennis EA, Wright J, Retzlaff CL, McManus OB, Lin Z, Huang X, Wu M, Li M, Daniels JS, Lindsley CW, Hopkins CR, Blakely RD. Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter. ACS Chem Neurosci. 2015 Mar 18;6(3):417-27. [2] Elizabeth Ennis Miss, Jane Wright, James Tarr, Charles Locuson, Corey Hopkins, J Daniels, Craig Lindsley and Randy Blakely. A Novel Approach to Cholinergic Signaling Modulation: Development and Characterization of ML352, a Novel, Noncompetitive Inhibitor of the Presynaptic Choline Transporter. The FASEB Journal vol. 29 no. 1 Supplement 932.6