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IAA-94 (Synonyms: R(+)-IAA 94)

Catalog No.GC15308

IAA-94 (Indanyloxyacetic acid-94) is an intracellular chloride channel blocker.

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IAA-94 Chemical Structure

Cas No.: 54197-31-8

Size Price Stock Qty
10mM (in 1mL DMSO)
$94.00
In stock
10mg
$85.00
In stock
50mg
$285.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Description of IAA-94

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.

Protocol of IAA-94

Cell experiment [1]:

Cell lines

murine microglial cell line BV-2, Primary microglial cell

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.

Reaction Conditions

30 µM for 3 h

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]:

Animal models

Male CD-1 mice weighing 25-30 g

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.

Dosage form

1, 3, 10 µg in 5 µl, i.t.

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.

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.
[2]:Yamazaki M, Mizoguchi H, Ohsawa M, et al. Implications of Ca2+-activated Cl- channels in the δ-opioid receptor-mediated antinociception in the mouse spinal cord[J]. Neuroscience letters, 2000, 295(3): 113-115.

Chemical Properties of IAA-94

Cas No. 54197-31-8 SDF
Synonyms R(+)-IAA 94
Chemical Name 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
Formula C17H18Cl2O4 M.Wt 357.2
Solubility ≤15mg/ml in ethanol;15mg/ml in DMSO;15mg/ml in dimethyl formamide Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table of IAA-94

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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
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