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| Targets |
MONNA specifically targets the anoctamin-1 (ANO1/TMEM16A) calcium-activated chloride channel (CaCC). It is a selective inhibitor of ANO1, with an IC50 of 0.08 microM for xANO1 in Xenopus oocytes. MONNA is selective for ANO1 over other chloride channels, including bestrophin-1, chloride channel protein 2 (ClC-2), and the cystic fibrosis transmembrane conductance regulator (CFTR), as these channels are not appreciably blocked by 10-30 microM MONNA. ANO1 is implicated in multiple physiological processes, including epithelial chloride secretion, smooth muscle contraction, and cancer cell proliferation.
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| ln Vitro |
In cell-free electrophysiological assays using Xenopus laevis oocytes expressing xANO1, MONNA fully blocks xANO1 chloride currents with an IC50 of 0.08 microM (80 nM). Selectivity tests reveal that other chloride channels, including bestrophin-1, chloride channel protein 2 (ClC-2), and CFTR, are not appreciably blocked by 10-30 microM MONNA. This indicates a high degree of selectivity for ANO1 over other chloride channels. In HEK293 cells expressing human ANO1, MONNA blocks rhTMEM16A channel currents with an IC50 of 1.27 microM. Structure-activity relationship (SAR) studies revealed that the -NO2 group at position 5 of the naphthyl group is critical for potent blocking activity.
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| ln Vivo |
Specific in vivo activity data for MONNA has not been published. However, as a potent and selective ANO1 blocker, it is hypothesized to modulate epithelial chloride transport and smooth muscle contraction in vivo. ANO1 is known to be involved in the pathogenesis of hypertension, asthma, gastrointestinal motility disorders, and certain cancers. MONNA may be used in animal models to study the role of ANO1 in these diseases and to validate ANO1 as a therapeutic target.
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| Enzyme Assay |
The specific protocol for assessing ANO1 inhibition uses the two-electrode voltage-clamp (TEVC) technique in Xenopus laevis oocytes. ANO1 cRNA is injected into defolliculated stage V-VI oocytes. After 2-4 days of expression, oocytes are placed in a recording chamber perfused with ND96 solution (96 mM NaCl, 2 mM KCl, 1.8 mM CaCl2, 1 mM MgCl2, 5 mM HEPES, pH 7.6). Intracellular calcium concentration is elevated to activate ANO1 channels either by injection of CaCl2 (50 nL of 100 mM) or by including Ca2+ in the pipette solution. MONNA is dissolved in DMSO (100 mM stock) and diluted to final concentrations of 0.1-1000 nM in perfusion solution. Voltage steps from -80 to +80 mV are applied, and current amplitudes are measured. The IC50 (0.08 microM) is calculated from concentration-response curves. For mammalian expression systems, whole-cell patch-clamp recordings in HEK293 cells expressing hANO1 are used.
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| Cell Assay |
For in vitro cellular assays, human bronchial epithelial cells (e.g., 16HBE14o- or Calu-3 cells) or HEK293 cells stably expressing ANO1 are seeded on glass coverslips. Whole-cell patch-clamp recordings are performed. The external solution contains (in mM): 140 NaCl, 2 CaCl2, 1 MgCl2, 10 HEPES, 10 glucose (pH 7.4). Pipettes (3-5 Momega) are filled with internal solution containing (in mM): 130 CsCl, 1 MgCl2, 0.5 EGTA, 5 HEPES, 2 Mg-ATP (pH 7.2). The free Ca2+ concentration is adjusted to 0.5-1 uM to activate ANO1. MONNA is applied via perfusion at concentrations of 0.01-10 uM. The reduction in current amplitude is measured, and the IC50 is calculated. For high-throughput screening, a YFP-based halide influx assay can be used in ANO1-expressing cells.
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| Animal Protocol |
An in vivo protocol for MONNA would involve a mouse model of airway hyperresponsiveness (asthma). Female BALB/c mice are sensitized with ovalbumin (OVA) and challenged with aerosolized OVA. MONNA is dissolved in a suitable vehicle (e.g., 5% DMSO/95% saline) and administered via intraperitoneal (1-10 mg/kg) or intranasal (0.1-1 mg/kg) routes, 30-60 minutes before OVA challenge. Airway resistance is measured using a whole-body plethysmograph (Penh). Bronchoalveolar lavage fluid (BALF) is collected after the experiment to measure inflammatory cell counts and cytokine levels. Lung tissues are collected for histopathological examination (H&E, PAS staining). The compound should reduce airway hyperresponsiveness if ANO1 plays a role in asthma pathogenesis.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for MONNA is not available. As a small molecule (molecular weight 382.33), it is expected to have moderate oral bioavailability and good cell membrane permeability. For in vivo studies, it is typically formulated in 5% DMSO/95% saline or in 10% DMSO/40% PEG300/5% Tween-80/45% saline for intraperitoneal or intravenous administration. The nitro group in MONNA may undergo metabolic reduction, which could affect its metabolic stability. Standard PK studies would involve IV/PO administration in mice followed by LC-MS/MS analysis to determine T1/2, Cmax, AUC, and oral bioavailability.
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| Toxicity/Toxicokinetics |
Toxicology data for MONNA has not been published. As an inhibitor of ANO1, which is widely expressed in epithelial tissues, smooth muscle, and cancer cells, the primary safety concern would be on-target toxicity due to disruption of normal ANO1 function. ANO1 is involved in epithelial fluid secretion, smooth muscle contraction, and cell proliferation. Chronic inhibition could potentially lead to gastrointestinal disturbances (due to impaired intestinal motility) or respiratory issues (due to altered airway surface liquid secretion). Standard toxicity assessment would include in vitro hERG testing, CYP inhibition screening, and a 14-day repeat-dose toxicity study in rodents.
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| References | |
| Additional Infomation |
MONNA is a research-grade chemical and is not approved for clinical use. Its molecular formula is C18H13N2O6 with a molecular weight of 353.31. It is a potent and selective blocker of anoctamin-1 (ANO1/TMEM16A) calcium-activated chloride channels (CaCCs) with an IC50 of 0.08 uM (80 nM) for xANO1 in Xenopus laevis oocytes. MONNA displays >100-fold selectivity for ANO1 over bestrophin-1, ClC-2, and CFTR. The compound is stored at -20degC and is soluble in DMSO. MONNA is a valuable tool for studying the physiological functions of ANO1/CaCC in health and disease.
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| Molecular Formula |
C18H14N2O5
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| Molecular Weight |
338.31
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| Exact Mass |
338.09
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| CAS # |
1572936-83-4
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| PubChem CID |
72165188
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| Appearance |
Brown to dark brown solid powder
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| LogP |
4.794
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
494
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC(=CC2=CC=CC=C21)NC3=C(C=C(C=C3)[N+](=O)[O-])C(=O)O
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| InChi Key |
JIVRLHBAUUZTNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14N2O5/c1-25-17-9-12(8-11-4-2-3-5-14(11)17)19-16-7-6-13(20(23)24)10-15(16)18(21)22/h2-10,19H,1H3,(H,21,22)
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| Chemical Name |
2-[(4-methoxynaphthalen-2-yl)amino]-5-nitrobenzoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 55.56 mg/mL (164.23 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9559 mL | 14.7793 mL | 29.5587 mL | |
| 5 mM | 0.5912 mL | 2.9559 mL | 5.9117 mL | |
| 10 mM | 0.2956 mL | 1.4779 mL | 2.9559 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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