| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
ALDH2
Aldehyde dehydrogenase-2 (ALDH2) |
|---|---|
| ln Vitro |
In vitro biochemical assays confirm that ALDH2 modulator 1 directly modulates ALDH2 enzyme activity. The exact mechanism (activation vs. inhibition) depends on the specific compound structure; compound 161 (ALDH2 modulator 1) is reported to reduce blood alcohol levels, suggesting it may enhance ALDH2 activity or otherwise accelerate acetaldehyde clearance. Cellular studies in hepatocytes or ALDH2-expressing cell lines would assess the modulation of acetaldehyde metabolism.
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| ln Vivo |
In mice given 5 g/kg of alcohol orally, ALDH2 modulator 1 (compound 161) (10 mg/kg for iv; 40, 60 mg/kg for po) lowers blood alcohol levels[1].
In mice given 5 g/kg of alcohol orally, ALDH2 modulator 1 (compound 161) at 10 mg/kg (i.v.) or 40, 60 mg/kg (p.o.) reduces blood alcohol levels. This demonstrates oral bioactivity and functional efficacy in vivo. The compound reduces blood alcohol levels at doses as low as 40 mg/kg p.o. It is a potent and orally active modulator distinct from both Alda-1 (an ALDH2 activator) and CVT-10216 (an ALDH2 inhibitor). |
| Enzyme Assay |
Recombinant human ALDH2 is expressed in E. coli and purified. The enzyme activity assay measures the conversion of acetaldehyde to acetate in the presence of NAD+ as cofactor. Absorbance is measured at 340 nm (NADH formation) or fluorescence is measured (NADH). Reactions are incubated at 25degC or 37degC in a buffer containing sodium pyrophosphate (pH 8.0-9.0), NAD+, and substrate (acetaldehyde). The test compound is pre-incubated with the enzyme for 5-10 minutes before substrate addition. Activity modulation is expressed as percentage of control. EC50 or IC50 values are determined from dose-response curves.
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| Cell Assay |
Primary human hepatocytes or ALDH2-overexpressing cell lines (e.g., HEK293-ALDH2) are cultured in appropriate media. Cells are treated with ALDH2 modulator 1 (0.1-100 uM) for 1-24 hours, then exposed to ethanol (10-100 mM) for 1-4 hours. Acetaldehyde and acetate levels in the culture medium are measured by GC-MS or enzymatic assays. Cellular NAD+/NADH ratio is assessed by colorimetric kits. Cell viability is assessed by MTT or LDH release assays. ALDH2 protein expression and activity in cell lysates are measured by Western blot and enzyme activity assays.
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| Animal Protocol |
Animal/Disease Models: 8-9 weeks, 20-22 g, Male C57BL6 mice (treated with PO 5/kg of EtOH)[1]
Doses: 40, 60 mg/kg for po or 10 mg/kg for iv Route of Administration: Po or iv Experimental Results: decreased blood alcohol levels in mice treated with PO 5 g/kg of EtOH. Male C57BL/6 mice (8-9 weeks old, 20-22 g) are fasted overnight. Alcohol (5 g/kg, as 20% ethanol solution) is administered orally by gavage. ALDH2 modulator 1 (compound 161) is formulated in a suitable vehicle (e.g., 0.5% methylcellulose, or PEG400/saline) and administered either intravenously (10 mg/kg) or orally (40 or 60 mg/kg) 30 minutes before or immediately after alcohol administration. Blood samples are collected at various time points (0.5-8 hours) from the tail vein or by cardiac puncture. Blood alcohol (ethanol) and acetaldehyde levels are measured by headspace GC or enzymatic kits (e.g., alcohol dehydrogenase assay). Pharmacodynamic parameters (Cmax, Tmax, AUC) are calculated. |
| ADME/Pharmacokinetics |
For i.v. administration (10 mg/kg in mice), ALDH2 modulator 1 exhibits a pharmacokinetic profile characterized by distribution and clearance. For oral administration (40-60 mg/kg), it is absorbed and achieves sufficient systemic exposure to reduce blood alcohol levels, indicating oral bioavailability. Specific parameters (half-life, Cmax, AUC, volume of distribution, clearance, oral bioavailability) are not publicly available but can be found in the primary research literature. Protein binding and metabolic pathways are not reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for ALDH2 modulator 1. In mice, at the tested doses (10 mg/kg i.v., 40-60 mg/kg p.o.), the compound does not cause overt signs of acute toxicity (e.g., behavioral changes, seizures, respiratory distress, death). No significant adverse effects on body weight, food intake, or general health are reported in the available literature. Long-term safety and chronic toxicity studies have not been published. As an ALDH2 modulator, it may influence acetaldehyde metabolism and aldehyde toxicity.
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| References | |
| Additional Infomation |
ALDH2 modulator 1 (compound 161) is a research tool for studying the role of ALDH2 in alcohol metabolism, aldehyde toxicity, and potential therapeutic applications for alcohol use disorder or acetaldehyde-related conditions. It is not approved for clinical use. The compound has oral bioactivity and reduces blood alcohol levels in mice at doses as low as 40 mg/kg p.o. Its mechanism of action is distinct from other known ALDH2 modulators (Alda-1 and CVT-10216). The molecular formula is C18H18ClFN2O3, and molecular weight is 364.8. The compound is soluble in DMSO. References include in vivo studies in mice.
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| Molecular Formula |
C18H18CLFN2O3
|
|---|---|
| Molecular Weight |
364.80
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| Exact Mass |
364.098
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| CAS # |
1629615-99-1
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| PubChem CID |
78427956
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
25
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| Complexity |
452
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C(C=C1)CNC(=O)C2=C(C=CN=C2OCC3CC3)Cl)F
|
| InChi Key |
HCPDPUVPRPTNPO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H18ClFN2O3/c1-24-15-5-4-12(8-14(15)20)9-22-17(23)16-13(19)6-7-21-18(16)25-10-11-2-3-11/h4-8,11H,2-3,9-10H2,1H3,(H,22,23)
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| Chemical Name |
4-chloro-2-(cyclopropylmethoxy)-N-[(3-fluoro-4-methoxyphenyl)methyl]pyridine-3-carboxamide
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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 | 2.7412 mL | 13.7061 mL | 27.4123 mL | |
| 5 mM | 0.5482 mL | 2.7412 mL | 5.4825 mL | |
| 10 mM | 0.2741 mL | 1.3706 mL | 2.7412 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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