GLPBio

MONNA

Catalog No.: GC18358Purity:>98%
COASDSData Sheet
MONNA ist ein potenter Blocker des Transmembranproteins 16A (TMEM16A, Anoctamin-1) mit einer IC50 von 80 nM.

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MONNA
Cas No.: 1572936-83-4
10mM (in 1mL DMSO)In Stock
$57.00
1
1mgIn Stock
$30.00
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5mgIn Stock
$77.00
1
10mgIn Stock
$112.00
1
25mgIn Stock
$245.00
1
50mgIn Stock
$385.00
1
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Beschreibung (Description)

MONNA is a specific blocker of ANO1 (anoctamin-1/TMEM16A) calcium-activated chloride channels, with an IC50 of 0.08μM for xANO1 in Xenopus laevis oocytes[1]. MONNA modulates epithelial chloride transport and smooth muscle contraction by selectively blocking ANO1-mediated chloride currents[2]. MONNA is commonly used in research on diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia[3][4].

In vitro, MONNA (1μM; 30s) caused reproducible elevations in intracellular Ca2+ concentration in isolated mouse bronchial smooth muscle cells[5].

In vivo, MONNA (1μM; 30min perfusion) reversed the U46619-induced decrease in coronary flow in Langendorff-perfused rat hearts[6]. MONNA (10μg/day; 3 days; starting on day 4 after SNL; intrathecal injection) reduced SNL-induced up-regulation of anoctamin-1, ATF-3, and caspase-3 protein expression in injured L5 dorsal root ganglia of rats[7].

References:
[1] Oh SJ, Hwang SJ, Jung J, et al. MONNA, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1. Mol Pharmacol. 2013;84(5):726-735.
[2] Liu Y, Liu Z, Wang K. The Ca2+-activated chloride channel ANO1/TMEM16A: An emerging therapeutic target for epithelium-originated diseases?. Acta Pharm Sin B. 2021;11(6):1412-1433.
[3] Galietta LJV. TMEM16A (ANO1) as a therapeutic target in cystic fibrosis. Curr Opin Pharmacol. 2022;64:102206.
[4] Boedtkjer DM, Kim S, Jensen AB, Matchkov VM, Andersson KE. New selective inhibitors of calcium-activated chloride channels - T16A(inh) -A01, CaCC(inh) -A01 and MONNA - what do they inhibit?. Br J Pharmacol. 2015;172(16):4158-4172.
[5] Dwivedi R, Drumm BT, Alkawadri T, et al. The TMEM16A blockers benzbromarone and MONNA cause intracellular Ca2+-release in mouse bronchial smooth muscle cells. Eur J Pharmacol. 2023;947:175677.
[6] Askew Page HR, Dalsgaard T, Baldwin SN, et al. TMEM16A is implicated in the regulation of coronary flow and is altered in hypertension. Br J Pharmacol. 2019;176(11):1635-1648.
[7] García G, Martínez-Rojas VA, Oviedo N, Murbartián J. Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain. Brain Res. 2018;1696:38-48.

Protokoll (Protocol)

Cell experiment [1]:

Cell lines

Single airway smooth muscle cells

Preparation Method

Single airway smooth muscle cells were isolated using a collagenase/proteinase mixture consisting of (per 5mL of Hanks Ca2+-free solution): 15mg/ml of collagenase (type II), 10mg/ml bovine serum albumin, 10mg/ml trypsin inhibitor and 1mg/ml proteinase. In order to examine the effects of MONNA on cytosolic [Ca2+] in isolated cells, MONNA (1μM) was applied three times for 30s. Cells were plated and incubated in 0.4μM fluo-4AM (Molecular Probes) for 6–8min at room temperature in Hank’s Ca2+-free solution to which 100μM Ca2+ was added. During experiments, dishes containing cells were continuously perfused with Hanks solution (Solution C) at 35±2℃. Additionally, the cell under study was continuously superfused with Hanks solution by means of a custom built close delivery system with a pipette tip diameter of 200μm placed approximately 300μm from the cell. The Hanks solution in the close delivery system could be switched to a drug-containing solution with a dead-space time of less than 5s. Cells were imaged using an iXon 887 EMCCD camera coupled to a Nipkow spinning disk confocal head.

Reaction Conditions

1μM; 30s

Applications

MONNA caused reproducible elevations in intracellular Ca2+ concentration in isolated mouse bronchial smooth muscle cells.
Animal experiment [2]:

Animal models

Female Wistar rats

Preparation Method

Female Wistar rats of 130-150g of weight (6-7 weeks) were housed in cages on a standard 12/12h light/dark cycle and had free access to food and water before experiments. Rats were sacrificed in a CO2 chamber at the end of experiments. Neuropathic pain was induced by L5/L6 spinal nerve ligation [SNL]. In order to determine the effect of MONNA in nerve injuryinduced neuropathic pain, rats were treated with MONNA (1-10μg; i.t.) or vehicle (1% or 15% DMSO; i.t.) daily for 3 days, starting on day 4 after nerve injury (SNL). Then, tactile allodynia was assessed from 7 to 21 days after injury.

Dosage form

1-10μg/day; 3 days; starting on day 4 after SNL; intrathecal injection

Applications

MONNA reverted SNL-induced tactile allodynia in a dose-dependent manner in injured L5 dorsal root ganglia of rats.

References:
[1] Dwivedi R, Drumm BT, Alkawadri T, et al. The TMEM16A blockers benzbromarone and MONNA cause intracellular Ca2+-release in mouse bronchial smooth muscle cells. Eur J Pharmacol. 2023;947:175677.
[2] García G, Martínez-Rojas VA, Oviedo N, Murbartián J. Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain. Brain Res. 2018;1696:38-48.

Chemische Eigenschaften (Chemical Properties)

CAS-Nr.
1572936-83-4
Chemischer Name
2-[(4-methoxy-2-naphthalenyl)amino]-5-nitro-benzoic acid
SMILES
COC1=CC(NC2=C(C(O)=O)C=C([N+]([O-])=O)C=C2)=CC3=CC=CC=C31
Summenformel
C18H14N2O5
Molekulargewicht
338.3
Löslichkeit
DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml,Ethanol: slightly soluble
Lagerung
Store at -20°C
Allgemeine Hinweise
Wählen Sie anhand der Löslichkeitsdaten des Produkts ein geeignetes Lösungsmittel. Aliquotieren Sie die Stammlösung nach der Herstellung, um wiederholte Gefrier-Auftau-Zyklen zu vermeiden.
Verwenden Sie Stammlösungen bei Lagerung bei -80°C innerhalb von 6 Monaten bzw. bei -20°C innerhalb von 1 Monat.
Zur Verbesserung der Löslichkeit das Röhrchen auf 37°C erwärmen und für eine angemessene Dauer beschallen.
Versandbedingungen
Evaluierungsmuster werden mit Kühlakkus versandt. Andere verfügbare Größen werden bei Raumtemperatur oder auf Anfrage mit Kühlakkus versandt.

Rechner (Calculators)Molarität / Verdünnung / Molekulargewicht / Einheitenumrechnung / In-vivo-Formulierung / Löslichkeit

g/mol

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