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Alda 1 Sale

(Synonyms: N-(1,3-苯并二氧杂环戊烯-5-基甲基)-2,6-二氯苯甲酰胺) 目录号 : GC16597

Alda 1是一种醛脱氢酶2(ALDH2)激活剂。

Alda 1 Chemical Structure

Cas No.:349438-38-6

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10mM (in 1mL DMSO)
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5mg
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10mg
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50mg
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Description

Alda 1 is an aldehyde dehydrogenase 2 (ALDH2) activator [1]. Alda 1 specifically activating the ALDH2 enzyme in mitochondria, enhances the enzyme's ability to metabolize toxic aldehydes such as acetaldehyde, thereby reducing cellular damage caused by these substances [2-3]. Alda 1 is primarily used to study diseases associated with abnormal acetaldehyde metabolism [4].

In human pulmonary alveolar epithelial cells, Alda 1 (20μM; 1h) pretreatment can alleviate lung ischemia-reperfusion injury [5]. In SH-SY5Y cells, pretreatment with Alda 1 (20 μM; 24 h) restored ALDH2 activity and content, increased mitochondrial membrane potential, and reduced reactive oxygen species in cells [6].

In C57BL/6J mice, after Alda 1 (5mg/kg; ip; single injection) administration elevated hepatic ALDH activity, which was blocked by the specific ALDH2 inhibitor, daidzin [7]. In liver ischemia-reperfusion injury (IRI) mice model, Alda 1 (30mg/kg; ip; single injection) mediated ALDH2 activation may improve hepatic IRI by scavenging reactive aldehydes and enhancing autophagy [8]. In hyperoxia mice model, Alda 1 (8mg/kg; sc; 48h) pretreatment attenuates hyperoxia-induced immune cell infiltration [9].

References:
[1]. Stachowicz A, Olszanecki R, Suski M, et al. Proteomic analysis of mitochondria-enriched fraction isolated from the frontal cortex and hippocampus of apolipoprotein E knockout mice treated with Alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH2)[J]. International Journal of Molecular Sciences, 2017, 18(2): 435.
[2]. Stachowicz A, Głombik K, Olszanecki R, et al. The impact of mitochondrial aldehyde dehydrogenase (ALDH2) activation by Alda-1 on the behavioral and biochemical disturbances in animal model of depression[J]. Brain, Behavior, and Immunity, 2016, 51: 144-153.
[3]. Ikeda T, Takahashi T, Tsujita M, et al. Effects of Alda-1, an aldehyde dehydrogenase-2 agonist, on hypoglycemic neuronal death[J]. PLoS One, 2015, 10(6): e0128844.
[4]. Stachowicz A, Olszanecki R, Suski M, et al. Mitochondrial aldehyde dehydrogenase activation by Alda‐1 inhibits atherosclerosis and attenuates hepatic steatosis in apolipoprotein E‐knockout mice[J]. Journal of the American Heart Association, 2014, 3(6): e001329.
[5]. Ding J, Zhang Q, Luo Q, et al. Alda-1 attenuates lung ischemia-reperfusion injury by reducing 4-hydroxy-2-nonenal in alveolar epithelial cells[J]. Critical care medicine, 2016, 44(7): e544-e552.
[6]. Deza-Ponzio R, Albrecht P A, Fernandez-Hubeid L E, et al. ALDH2 inhibition by lead and ethanol elicits redox imbalance and mitochondrial dysfunction in SH-SY5Y human neuroblastoma cell line: Reversion by Alda-1[J]. Neurotoxicology, 2023, 97: 12-24.
[7]. Zhong W, Zhang W, Li Q, et al. Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice[J]. Journal of hepatology, 2015, 62(6): 1375-1381.
[8]. Li M, Xu M, Li J, et al. Alda‐1 Ameliorates Liver Ischemia‐Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice[J]. Journal of Immunology Research, 2018, 2018(1): 9807139.
[9]. Sidramagowda Patil S, Hernández-Cuervo H, Fukumoto J, et al. Alda-1 attenuates hyperoxia-induced acute lung injury in mice[J]. Frontiers in pharmacology, 2021, 11: 597942.

Alda 1是一种醛脱氢酶2(ALDH2)激活剂 [1]。Alda 1特异性激活线粒体中的ALDH2酶,增强该酶代谢乙醛等毒性醛类物质的能力,从而减轻这些物质对细胞造成的损伤 [2-3]。Alda 1主要用于研究与乙醛代谢异常相关的疾病 [4]

在人肺泡上皮细胞中,Alda 1(20μM;1h)预处理可减轻肺缺血-再灌注损伤 [5]。在SH-SY5Y细胞中,Alda 1(20μM;24h)预处理可恢复ALDH2活性和含量,提高线粒体膜电位,并降低细胞中的活性氧 [6]

在C57BL/6J小鼠中,给予Alda 1(5mg/kg;ip;单次注射)后,肝脏ALDH活性升高,而该活性可被特异性ALDH2抑制剂大豆苷元阻断 [7]。在肝脏缺血-再灌注损伤(IRI)小鼠模型中,Alda 1(30mg/kg;ip;单次注射)介导的ALDH2激活可能通过清除活性醛和增强自噬来改善肝脏IRI [8]。在高氧小鼠模型中,Alda 1(8mg/kg;sc;48h)预处理可减轻高氧诱导的免疫细胞浸润 [9]

实验参考方法

Cell experiment [1]:

Cell lines

Human pulmonary alveolar epithelial cells

Preparation Method

Primary human pulmonary alveolar epithelial cells were cultured at 37℃ and 5% CO2, in alveolar epithelial cell medium and endothelial cell-growth medium MV2. Hypoxia was induced by exposing the cells for 24 hours to serum-deprived media in a sealed anaerobic jar fitted with an AnaeroPack to scavenge any free oxygen. The cells were then washed with PBS and were reoxygenated for 2 hours under normal conditions in complete medium. Alda 1, 20μM, was added to the medium for 1 hour before hypoxic exposure of the hypoxia/reoxygenation (H/R) + Alda 1 group.

Reaction Conditions

20μM; 1h

Applications

Alda 1 pretreatment can alleviate lung ischemia-reperfusion injury.
Animal experiment [2]:

Animal models

C57BL/6J mice

Preparation Method

Mice were given 5mg/kg body weight (BW) Alda 1 (dissolved in dimethyl sulfoxide, DMSO) at 9:00 am via three routes, intraperitoneal injection (i.p.). Livers were collected 3 hours after treatments, and hepatic ALDH activity was immediately measured. To assess the specificity of Alda 1 on activating ALDH2, mice were given an ALDH2 specific inhibitor, daidzin, at 50mg/kg BW (dissolved in DMSO) via i.p. along with 5mg/kg BW Alda 1 administration at 9:00 am (n = 4). Three hours later, liver and ileum were collected, mitochondrial and cytosolic fractions from the liver were isolated, and ALDH activity was immediately measured.

Dosage form

5mg/kg; ip; single injection

Applications

One dose of Alda 1 administration elevated hepatic ALDH activity, which was blocked by the specific ALDH2 inhibitor, daidzin.

References:
[1]. Ding J, Zhang Q, Luo Q, et al. Alda-1 attenuates lung ischemia-reperfusion injury by reducing 4-hydroxy-2-nonenal in alveolar epithelial cells[J]. Critical care medicine, 2016, 44(7): e544-e552.
[2]. Zhong W, Zhang W, Li Q, et al. Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice[J]. Journal of hepatology, 2015, 62(6): 1375-1381.

化学性质

Cas No. 349438-38-6 SDF
别名 N-(1,3-苯并二氧杂环戊烯-5-基甲基)-2,6-二氯苯甲酰胺
化学名 N-(benzo[d][1,3]dioxol-5-ylmethyl)-2,6-dichlorobenzamide
Canonical SMILES ClC1=CC=CC(Cl)=C1C(NCC2=CC=C3OCOC3=C2)=O
分子式 C15H11Cl2NO3 分子量 324.16
溶解度 ≥ 15.15mg/mL in DMSO 储存条件 Store at -20°C
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1 mM 3.0849 mL 15.4245 mL 30.849 mL
5 mM 617 μL 3.0849 mL 6.1698 mL
10 mM 308.5 μL 1.5424 mL 3.0849 mL
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