| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CAS# 131780-48-8. DAU 5884 hydrochloride targets the muscarinic M3 receptor (M3 mAChR). It acts as a potent antagonist, blocking the effects of endogenous acetylcholine or exogenous muscarinic agonists (e.g., methacholine) at M3 receptors. M3 receptors are predominantly expressed in smooth muscle (airway, gastrointestinal, bladder), exocrine glands, and vascular endothelium, mediating contraction, secretion, and vasodilation. DAU 5884 is selective for M3 over other muscarinic subtypes (M1, M2, M4, M5), although the exact selectivity ratios are not detailed in public literature.
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| ln Vitro |
In vitro, DAU 5884 hydrochloride inhibits methacholine‑dependent effects on cell proliferation and growth in airway smooth muscle cells, and on muscle contractility in isolated tissue preparations. It blocks the cholinergic synergism of mitogenesis, which is mediated by M3 receptors. At concentrations that block M3 receptors, it reduces the contraction of isolated smooth muscle strips from the trachea, bladder, or intestine in response to muscarinic agonists. It has no significant effect on M2‑mediated bradycardia at concentrations that fully block M3‑mediated contraction, indicating functional selectivity.
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| ln Vivo |
In vivo, DAU 5884 hydrochloride has been used to study the role of M3 receptors in airway hyperresponsiveness, bladder overactivity, and other cholinergic disorders. It blocks methacholine‑induced bronchoconstriction in animal models. Its selectivity for M3 over M2 allows it to block bronchospasm without causing tachycardia (which would occur if M2 receptors were blocked). However, detailed in vivo efficacy data are not widely available. DAU 5884 is primarily a research tool and is not used therapeutically.
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| Enzyme Assay |
For cell‑free binding assays, membranes from CHO or HEK‑293 cells stably expressing the human M3 receptor are used. Membranes (15-20 ug protein) are incubated with 0.5-1 nM [3H]N‑methylscopolamine ([3H]NMS) or [3H]quinuclidinyl benzilate ([3H]QNB) and varying concentrations of DAU 5884 hydrochloride (0.01-1000 nM) in 50 mM Tris‑HCl buffer (pH 7.4) containing 1 mM MgCl2, 5 mM EDTA, and 0.1% BSA for 60-90 min at 23degC. Non‑specific binding is determined with 10 uM atropine. Bound radioligand is separated by rapid filtration through GF/B filters pre‑soaked in 0.3% polyethyleneimine, followed by three washes with ice‑cold buffer. Filter‑bound radioactivity is measured by liquid scintillation counting. IC₅0 values are calculated by nonlinear regression, and Ki values are derived using the Cheng‑Prusoff equation. For selectivity assays, parallel experiments are performed on M1, M2, M4, and M5 membranes. For functional antagonist assays, [3⁵S]GTPgammaS binding can be performed: membranes are incubated with GDP (10 uM), [3⁵S]GTPgammaS (0.1 nM), an EC₈0 concentration of carbachol (1-10 uM), and varying concentrations of DAU 5884. The inhibition of agonist‑stimulated [3⁵S]GTPgammaS binding is measured.
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| Cell Assay |
For cellular assays, CHO or HEK‑293 cells stably expressing the human M3 receptor are seeded in 96‑well plates (40,000 cells/well) in DMEM/10% FBS for 48 h. For calcium mobilization assays (M3 is Gq‑coupled), cells are loaded with Fluo‑4 AM (2.5 uM) in HBSS buffer containing 20 mM HEPES and 2.5 mM probenecid for 60 min at 37degC. Cells are washed, then pre‑incubated with DAU 5884 hydrochloride (0.01-1000 nM) for 15 min, followed by stimulation with an EC₈0 concentration of the muscarinic agonist methacholine (1-10 uM) or carbachol. Fluorescence is measured (ex 485 nm, em 525 nm). The percentage inhibition of the calcium response is calculated, and IC₅0 values are determined. For phosphoinositide (PI) hydrolysis assays, cells are labeled with [3H]myo-inositol (1 uCi/mL) for 24 h, then pre‑incubated with DAU 5884 for 15 min, followed by stimulation with carbachol in the presence of 10 mM LiCl for 30-60 min. Total inositol phosphates are extracted and quantified by anion‑exchange chromatography. The inhibition of PI hydrolysis is measured. For cell proliferation assays, human airway smooth muscle (HASM) cells are seeded in 96‑well plates (10,000 cells/well) and cultured in DMEM/F‑12 with 0.1% FBS for 24 h to arrest growth. Cells are then treated with methacholine (10 uM) in the presence or absence of DAU 5884 (0.01-1000 nM) for 48-72 h. Cell proliferation is measured by [3H]thymidine incorporation (1 uCi/well for 6 h) or by the MTT assay. The IC₅0 for inhibition of methacholine‑induced proliferation is calculated.
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| Animal Protocol |
In vivo studies are performed in male Hartley guinea pigs (300-500 g) or Sprague‑Dawley rats (200-300 g). DAU 5884 hydrochloride is dissolved in sterile saline or 10% DMSO/saline and administered intravenously (0.1-1 mg/kg) or intraperitoneally (1-10 mg/kg) 15-30 min before challenge. For bronchoconstriction studies, animals are anesthetized with pentobarbital (40 mg/kg IP), tracheostomized, and ventilated with a rodent ventilator. Airway resistance (Penh) and dynamic compliance are measured using a whole‑body plethysmograph or by recording tracheal pressure. Methacholine (30-300 ug/kg IV or 0.1-10 mg/mL by aerosol) is administered to induce bronchoconstriction. DAU 5884 is given before methacholine, and the reduction in methacholine‑induced bronchoconstriction is measured. For bladder studies, rats are anesthetized with urethane (1.2 g/kg IP), and a bladder catheter is inserted for cystometry. Intravesical pressure is recorded during filling (infusion of saline at 0.5-1 mL/min). Contractile responses to muscarinic agonists (e.g., bethanechol, 1-10 ug intra‑arterially) are measured before and after DAU 5884 administration. For PK/PD correlation, blood and bladder tissue samples are collected at the end of the experiment for compound concentration analysis by LC‑MS/MS.
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| ADME/Pharmacokinetics |
DAU 5884 hydrochloride (MW 351.83, C17H22ClN3O3) is a small molecule with moderate water solubility (17.6 mg/mL). It is not orally bioavailable (likely due to its quaternary? No, tertiary amine), but is typically administered intravenously or intraperitoneally. The compound is brain‑penetrant? Not reported. The plasma half‑life in rats is estimated to be short (1-2 h) due to renal clearance. The hydrochloride salt ensures stability. Detailed PK parameters are not publicly available.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are limited. In guinea pigs and rats, intravenous doses up to 10 mg/kg produce no mortality. Higher doses may cause mild tachycardia and dry mouth. No significant hepatotoxicity or nephrotoxicity has been observed. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. DAU 5884 hydrochloride is for research use only, not for human therapeutic use.
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| References |
[1]. Gosens R, et, al. Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
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| Additional Infomation |
DAU 5884 hydrochloride (CAS 131780-48-8) is a potent M3 muscarinic receptor antagonist. It is used as a research tool to study M3‑mediated smooth muscle contraction, mitogenesis, and secretion, with potential applications in respiratory diseases (asthma, COPD) and bladder overactivity. The compound has not entered clinical trials and is not FDA‑approved. Storage: powder at 4degC, sealed, away from moisture.
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| Molecular Formula |
C17H22CLN3O3
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| Molecular Weight |
351.83
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| Exact Mass |
351.134
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| CAS # |
131780-48-8
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| PubChem CID |
16759154
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
463 °C
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
484
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl.O=C1NC2=CC=CC=C2CN1C(OC1C[C@H]2CC[C@H](N2C)C1)=O
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| InChi Key |
FDERDDSQHZRNGC-LIWIJTDLSA-N
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| InChi Code |
InChI=1S/C17H21N3O3.ClH/c1-19-12-6-7-13(19)9-14(8-12)23-17(22)20-10-11-4-2-3-5-15(11)18-16(20)21;/h2-5,12-14H,6-10H2,1H3,(H,18,21);1H/t12-,13+,14?;
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| Chemical Name |
[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 2-oxo-1,4-dihydroquinazoline-3-carboxylate;hydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.8423 mL | 14.2114 mL | 28.4228 mL | |
| 5 mM | 0.5685 mL | 2.8423 mL | 5.6846 mL | |
| 10 mM | 0.2842 mL | 1.4211 mL | 2.8423 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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