IAA-94
(Synonyms: R-(+)-甲基吲唑酮,R(+)-IAA 94) 目录号 : GC15308
IAA-94 (Indanyloxyacetic acid-94) 是一种细胞内氯离子通道阻滞剂。
Cas No.:54197-31-8
Sample solution is provided at 25 µL, 10mM.
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IAA-94 (Indanyloxyacetic acid-94) is an intracellular chloride channel blocker [1]. IAA-94 inhibited CLIC-1-dependent chloride permeability with an apparent IC50 of 8.6 μM [2]. IAA-94 depressed the K+-induced force with an IC50 of 17.0 ± 1.2 μM [3].
In cells treated with IAA-94 (30 μM) with respect to control, the amount of intracellular Aβ1-42 phagocytosis was remarkably increased after 24 hr of incubation [4]. Inhibition of Cl- channels with pan-chloride channel blocker IAA-94 (50 μM) abolished the protection induced by 200 nM CsA pre-treatment in cardiomyocytes [5]. The anion channel blocker IAA-94 (200 μM) significantly blocked glutamate and taurine release against Astrocytes in hypotonic solution [6].
IAA-94 was shown to abrogate cardioprotection mediated by IPC and cyclosporin A (CsA) [7]. Adult male rat hearts were subjected to the left coronary artery occlusion for 45min followed by 3h of reperfusion. A single intravenous bolus of phosphate buffered saline (PBS) (control) or IAA-94 (20mg/kg body weight) was administered 5min before reperfusion. The infarct size (IS) was significantly higher in the IAA-94-treated group compared to control; the ratio of IS to area at risk was 58.1±7% in IAA-94 vs. 33.5±6% in control in this rat model [1].
References:
[1]. Ponnalagu D, Hussain A T, Thanawala R, et al. Chloride channel blocker IAA-94 increases myocardial infarction by reducing calcium retention capacity of the cardiac mitochondria[J]. Life sciences, 2019, 235: 116841.
[2]. Tulk B M, Schlesinger P H, Kapadia S A, et al. CLIC-1 functions as a chloride channel when expressed and purified from bacteria[J]. Journal of Biological Chemistry, 2000, 275(35): 26986-26993.
[3]. Doughty J M, Miller A L, Langton P D. Non‐specificity of chloride channel blockers in rat cerebral arteries: block of the L‐type calcium channel[J]. The Journal of physiology, 1998, 507(2): 433-439.
[4]. Paradisi S, Matteucci A, Fabrizi C, et al. Blockade of chloride intracellular ion channel 1 stimulates Aβ phagocytosis[J]. Journal of neuroscience research, 2008, 86(11): 2488-2498.
[5]. Diaz R J, Fernandes K, Lytvyn Y, et al. Enhanced cell-volume regulation in cyclosporin A cardioprotection[J]. Cardiovascular research, 2013, 98(3): 411-419.
[6]. Ye Z C, Oberheim N, Kettenmann H, et al. Pharmacological “cross‐inhibition” of connexin hemichannels and swelling activated anion channels[J]. Glia, 2009, 57(3): 258-269.
[7]. Diaz R J, Losito V A, Mao G D, et al. Chloride channel inhibition blocks the protection of ischemic preconditioning and hypo-osmotic stress in rabbit ventricular myocardium[J]. Circulation research, 1999, 84(7): 763-775.
IAA-94 (Indanyloxyacetic acid-94) 是一种细胞内氯离子通道阻滞剂[1]。 IAA-94 抑制 CLIC-1 依赖性氯离子渗透性，表观 IC50 为 8.6 μM [2]。 IAA-94 抑制 K+- 诱导力，IC50 为 17.0 ± 1.2 μM [3]。
相对于对照，在用 IAA-94 (30 μM) 处理的细胞中，细胞内 Aβ1-42 吞噬量在孵育 24 小时后显着增加 [4]。用泛氯离子通道阻滞剂 IAA-94 (50 μM) 抑制 Cl- 通道消除了 200 nM CsA 预处理对心肌细胞诱导的保护作用[5]。阴离子通道阻滞剂 IAA-94 (200 μM) 显着阻断谷氨酸和牛磺酸在低渗溶液中对星形胶质细胞的释放[6]。
IAA-94 被证明可以消除由 IPC 和环孢菌素 A (CsA) [7] 介导的心脏保护作用。对成年雄性大鼠心脏进行左冠状动脉闭塞 45 分钟，然后再灌注 3 小时。再灌注前 5 分钟给予单次静脉推注的磷酸盐缓冲盐水 (PBS)（对照）或 IAA-94（20mg/kg 体重）。与对照组相比，IAA-94 治疗组的梗塞面积 (IS) 明显更高；在该大鼠模型中，IS 与风险面积的比率在 IAA-94 中为 58.1±7%，而在对照组中为 33.5±6%[1]。
| Cell experiment [1]: | |
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Cell lines |
murine microglial cell line BV-2, Primary microglial cell |
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Preparation Method |
Flow cytometry was used to measure BV-2 cell uptake of fluorescent beads after stimulation with Aβ25-35, the active fragment of Aβ, and Aβ35-25, the reverse, inactive form. Cells were treated with aggregated Aβ25-35 (50 µM) for 30 min, 90 min, and 3 hr in the presence or not of the CLIC-1 inhibitor IAA-94 and with Aβ35-25 (50 µM) for 3 hr. Treatments were performed on cells in suspension at 37°C; afterward, cells were washed with medium. |
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Reaction Conditions |
30 µM for 3 h |
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Applications |
Primary microglia showed a phagocytic ability that remained substantially unmodified after Aβ treatment. Treatment with IAA-94 did not modify the phagocytic ability of these cells. |
| Animal experiment [2]: | |
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Animal models |
Male CD-1 mice weighing 25-30 g |
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Preparation Method |
Groups of mice were treated i.t. with a selective δ-opioid receptor agonist [D-Ala2]deltorphin II (10 µg) in 10% 2-hydroxypropyl-β-cyclodextrin/saline solution (5 µl), and the antinociception induced by [D-Ala2]deltorphin II was measured for 1 h after the treatment. In order to ascertain the role of Ca2+-activated Cl- channels in the expression of δ-opioid receptor-mediated antinociception, a selective Ca2+-activated Cl- channel blocker IAA-94(2% Tween 20/saline solution, 1, 3, 10 µg in 5 µl) was pretreated i.t. 10 min prior to the [D-Ala2]deltorphin II injection. |
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Dosage form |
1, 3, 10 µg in 5 µl, i.t. |
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Applications |
Mice injected [D-Ala2]deltorphin II showed a marked antinociception (peak effect: 79.5±11.1% MPE). The antinociception induced by [D-Ala2]deltorphin II was attenuated by i.t.-pretreatment with IAA-94 in a dose-dependent manner, and the peak effect was significantly reduced to 44.8±10.0% MPE by 10 µg of IAA-94. |
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References: [1]: Paradisi S, Matteucci A, Fabrizi C, et al. Blockade of chloride intracellular ion channel 1 stimulates Aβ phagocytosis[J]. Journal of neuroscience research, 2008, 86(11): 2488-2498. |
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| Cas No. | 54197-31-8 | SDF | |
| 别名 | R-(+)-甲基吲唑酮,R(+)-IAA 94 | ||
| 化学名 | 2-[[(2R)-6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl]oxy]-acetic acid | ||
| Canonical SMILES | ClC1=C(C([C@](C2CCCC2)(C)C3)=O)C3=CC(OCC(O)=O)=C1Cl | ||
| 分子式 | C17H18Cl2O4 | 分子量 | 357.2 |
| 溶解度 | ≤15mg/ml in ethanol;15mg/ml in DMSO;15mg/ml in dimethyl formamide | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7996 mL | 13.9978 mL | 27.9955 mL |
| 5 mM | 0.5599 mL | 2.7996 mL | 5.5991 mL |
| 10 mM | 0.28 mL | 1.3998 mL | 2.7996 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
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