切换导航

Etazolate hydrochloride

现货
Catalog No.
B6304
PDE-4抑制剂和选择性GABA-A受体调节剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL H2O)
¥ 500.00
现货
10mg
¥ 990.00
现货
50mg
¥ 4,190.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

Etazolate hydrochloride is a PDE-4 inhibitor and selective GABA-A receptor modulator [3].

PDE-4 modulates the release of inflammatory mediators through cAMP-dependent and -independent mechanisms. Selective targeting PDE-4 is a novel therapeutic approach in the treatment of inflammation-associated respiratory diseases, such as asthma and COPD (chronic obstructive pulmonary disease) [1].

In rat neuronal cortical cells, etazolate hydrochloride (0.2 μM) induced sAPPα through the stimulation of the α-secretase pathway, and exerted a neuroprotective effect against Aβ which was associated with sAPPα induction via the GABA-A receptor [2].

In 159 Alzheimer’s Disease patients, etazolate hydrochloride in combination with one AchEI (acetycholinesterase inhibitor) was shown to be safe and generally well tolerated in the Phase IIA study over a 3-month treatment period [3].

References:
[1] Dastidar S G, Rajagopal D, Ray A.  Therapeutic benefit of PDE4 inhibitors in inflammatory diseases.[J]. Current Opinion in Investigational Drugs, 2007, 8(5):364-72.
[2] Marcade M, Bourdin J, Loiseau N, et al.  Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing.[J]. Journal of Neurochemistry, 2008, 106(1):392-404.
[3] Vellas B; Sol O; Snyder PJ; Ousset PJ; Haddad R; Maurin M; Lemarié JC; Désiré L; Pando MP; EHT0202/002 study group.  EHT0202 in Alzheimer's disease: a 3-month, randomized, placebo-controlled, double-blind study.[J]. Current Alzheimer Research, 2011, 8(2):203-12.

文献引用

1. Alzoubi KH, Al Subeh ZY, et al. "Molecular targets for the interactive effect of etazolate during post-traumatic stress disorder: Role of oxidative stress, BDNF and histones." Behav Brain Res. 2019 Sep 2;369:111930. PMID:31047921
2. Alzoubi KH, Mokhemer E, et al. "Beneficial effect of etazolate on depression-like behavior and, learning, and memory impairment in a model of Parkinson's disease." Behav Brain Res. 2018 Sep 17;350:109-115. PMID:29758248
3. Alzoubi KH, Al Subeh ZY, et al. "Evaluating the protective effect of etazolate on memory impairment, anxiety- and depression-like behaviors induced by post traumatic stress disorder." Brain Res Bull. 2017 Oct;135:185-192. PMID:29107895

Chemical Properties

Physical AppearanceA solid
StorageStore at RT
M.Wt325.8
Cas No.35838-58-5
FormulaC14H19N5O2.HCl
Solubility≥3.9mg/mL in H2O
Chemical Nameethyl 1-ethyl-4-(2-(propan-2-ylidene)hydrazinyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate hydrochloride
SDFDownload SDF
Canonical SMILESO=C(C1=CN=C2N(CC)N=CC2=C1N/N=C(C)\C)OCC.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

Wistar大鼠胚胎的脑皮质细胞

溶解方法

在蒸馏水中的溶解度为50 mM。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。

反应时间

48 h,0~2 μM

应用

在皮质神经元中,0~2 μM etazolate hydrochloride可剂量依赖性地增加非淀粉样sAPPα。0.2 μM etazolate hydrochloride通过调控GABA-A受体,阻碍皮质神经元中Aβ的神经毒性,这与α-分泌酶活性和sAPPα的诱导相关。Etazolate hydrochloride通过刺激α分泌酶途径,诱导sAPPα的产生,但不影响淀粉样变性途径。

临床实验[2]:

临床模型

阿尔茨海默病患者

剂量

40 和 80 mg,每天两次,给药3个月,口服

应用

在IIA期的研究中,对159位阿尔茨海默病患者进行3个月的治疗,结果显示etazolate hydrochloride与AChEI(乙酰胆碱酯酶抑制剂)联用是安全的且耐受性良好。大多数精神病和神经病相关的副作用发生在高剂量组(etazolate hydrochloride 80 mg,2次/天),表明具有潜在的剂量效应关系。跟placebo组相比,胃肠道和心血管相关的副作用在etazolate hydrochloride 处理组中很少发生,表明AChEI与etazolate hydrochloride之间没有潜在的不良反应。

注意事项

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。

References:

[1] Marcade M, Bourdin J, Loiseau N, et al. Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing.[J]. Journal of Neurochemistry, 2008, 106(1):392-404.

[2] Vellas B; Sol O; Snyder PJ; Ousset PJ; Haddad R; Maurin M; Lemarié JC; Désiré L; Pando MP; EHT0202/002 study group. EHT0202 in Alzheimer's disease: a 3-month, randomized, placebo-controlled, double-blind study.[J]. Current Alzheimer Research, 2011, 8(2):203-12.

质量控制

化学结构

Etazolate hydrochloride

相关生物数据

Etazolate hydrochloride

相关生物数据

Etazolate hydrochloride

相关生物数据

Etazolate hydrochloride