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RSV A405

Cat No.:V38108 Purity: ≥98%
RSVA405 is a potent and orally bioactive AMPK activator with EC50 of 1 μM.
RSV A405
RSV A405 Chemical Structure CAS No.: 140405-36-3
Product category: JAK
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
RSVA405 is a potent and orally bioactive AMPK activator with EC50 of 1 μM. RSVA405 inhibits mTOR by promoting CaMKKβ-dependent AMPK activation, and promotes autophagy to increase Aβ degradation. RSVA405 has anti-inflammatory effects by inhibiting STAT3 function. RSVA405 can also be used in obesity research.
RSV A405 (RSVA405, CAS 140405-36-3) is a potent and orally bioactive AMPK activator with an EC50 of 1 μM. The molecular formula is C17H20N4O2 with a molecular weight of 312.37 g/mol. RSVA405 inhibits mTOR by promoting CaMKKβ-dependent AMPK activation and promotes autophagy to increase Aβ degradation. It also inhibits STAT3 function, providing anti-inflammatory effects. This compound is an analog of resveratrol that can significantly activate AMPK and inhibit acetyl-CoA carboxylase (ACC), a key regulator of fatty acid biogenesis.
Biological Activity I Assay Protocols (From Reference)
Targets
AMPK 1 μM (EC50, in cell-based assays)
RSV A405 targets multiple pathways. It is a potent AMPK (AMP-activated protein kinase) activator with an EC50 of 1 μM. It inhibits mTOR by promoting CaMKKβ-dependent AMPK activation. RSVA405 also inhibits STAT3, providing anti-inflammatory effects. Additionally, it inhibits acetyl-CoA carboxylase (ACC), a downstream target of AMPK and key regulator of fatty acid biosynthesis. This compound may have potential for treating obesity and metabolic disorders.
ln Vitro
RSVA405 (0.2-2 μM; 24 h) suppresses the development of adipocytes[2]. In 3T3-L1 cells, the production of fatty acid synthase (FAS), PPAR-γ, and fatty acid binding protein 4 (aP2) is strongly inhibited by RSVA405 (0.2-2 μM; 24 h)[2]. In activated RAW 264.7 macrophages, RSVA405 (1-3 μM; 16 h) suppresses LPS-induced STAT3 activity, intracellular signaling, and cytokine response[3]. With an EC50 of approximately 1 μM in APP-HEK293 cells, RSVA405 (1-3 μM; 24 h) suppresses mTOR, induces autophagy, and promotes the lysosomal breakdown of Aβ[4].
In vitro, RSV A405 demonstrates potent activation of AMPK with an EC50 of 1 μM. It promotes CaMKKβ-dependent AMPK activation, which leads to mTOR inhibition. This activation promotes autophagy, increasing the degradation of Aβ (amyloid-beta). RSVA405 also inhibits acetyl-CoA carboxylase (ACC) in non-differentiated and proliferating 3T3-L1 adipocytes. Through STAT3 inhibition, it exerts anti-inflammatory effects. These activities suggest potential applications in neurodegenerative diseases, metabolic disorders, and inflammation.
ln Vivo
In rats undergoing ischemia-reperfusion (I/R), RSVA405 (3 mg/kg; ip) reduces kidney damage and preserves renal function[1]. Mice on a high-fat diet have significantly less body weight gain when given RSVA405 (20–100 mg/kg/d; po for 11 weeks)[2].
In vivo, RSV A405 is orally bioactive and has demonstrated efficacy in animal models. It activates AMPK and promotes autophagy, potentially increasing Aβ degradation. Its anti-inflammatory effects via STAT3 inhibition may be beneficial in various inflammatory conditions. The compound has been studied for its potential in treating obesity by inhibiting fatty acid biosynthesis. In vivo studies would typically assess AMPK activation, autophagy induction, and anti-inflammatory effects in relevant animal models.
Enzyme Assay
Non-cellular enzyme/receptor binding assay protocols for RSV A405 involve measuring AMPK activation. AMPK activity can be assessed using kinase assays with recombinant AMPK and peptide substrates. The EC50 for AMPK activation is 1 μM. STAT3 inhibition can be measured using binding assays or phosphorylation studies. ACC inhibition can be assessed by measuring enzyme activity. Binding affinity studies can be performed using SPR or ITC.
Cell Assay
Cell Viability Assay[2]
Cell Types: 3T3-L1 preadipocytes
Tested Concentrations: 0.2, 0.5, 1, 2 μM
Incubation Duration: 24 h
Experimental Results: Increased the phosphorylation of AMPK and its substrate acetyl- CoA carboxylase (ACC). Inhibited the accumulation of lipid droplets in a dose-dependent manner, with an IC50 of 0.5 μM.
Cellular assay protocols for RSV A405 involve treating cells with the compound. Cells are incubated with RSVA405 at various concentrations, and AMPK activation is assessed by measuring phosphorylation of AMPK and its downstream targets (e.g., ACC) by western blot. mTOR inhibition is assessed by measuring phosphorylation of mTOR and its downstream targets. Autophagy is measured by LC3-II accumulation and p62 degradation. STAT3 inhibition is assessed by measuring STAT3 phosphorylation. Aβ degradation can be measured in neuronal cell models.
Animal Protocol
Animal/Disease Models: Male SD (Sprague-Dawley) rats (300-350 g) are induced I/ R injury[1]
Doses: 3 mg/kg
Route of Administration: Ip one hour before inducing I/R injury
Experimental Results: diminished the levels of creatinine and blood urea nitrogen (BUN), by 35.8% and 44.3% in serum, respectively. diminished the levels of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) by 33.0% and 59.8% in serum, respectively.
In vivo animal experiment protocols for RSV A405 involve administering the compound orally to rodents. Doses are determined based on PK studies. Efficacy studies may include mouse models of obesity, metabolic syndrome, or neurodegenerative diseases. Endpoints include measurement of AMPK activation in tissues, assessment of autophagy markers, measurement of Aβ levels, evaluation of anti-inflammatory effects, and assessment of metabolic parameters. Tissue samples are collected for biochemical analysis.
ADME/Pharmacokinetics
Pharmacokinetic properties of RSV A405 indicate it is orally bioactive. As a small molecule (MW 312.37 g/mol), it is expected to have reasonable oral bioavailability. The compound is a light yellow to yellow solid powder. Further PK studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion profile, including half-life (t½), maximum concentration (Cmax), and clearance (CL).
Toxicity/Toxicokinetics
Toxicity of RSV A405 has not been extensively reported. As a research compound, standard toxicological evaluation would include acute and sub-chronic toxicity studies in rodents, genotoxicity testing (Ames test, micronucleus assay), and cardiovascular safety assessments (hERG channel inhibition). The compound is for research use only and not for human therapeutic applications.
References

[1]. Novel resveratrol analogues attenuate renal ischemic injury in rats. J Surg Res. 2015 Feb;193(2):807-15.

[2]. Small-molecule activators of AMP-activated protein kinase (AMPK), RSVA314 and RSVA405, inhibit adipogenesis. Mol Med. Sep-Oct 2011;17(9-10):1022-30.

[3]. Identification of potent small-molecule inhibitors of STAT3 with anti-inflammatory properties in RAW 264.7 macrophages. FEBS J. 2012 Oct;279(20):3791-9.

[4]. Novel synthetic small-molecule activators of AMPK as enhancers of autophagy and amyloid-β peptide degradation. FASEB J. 2011 Jan;25(1):219-31.

Additional Infomation
RSV A405 (CAS: 140405-36-3) has a molecular formula of C17H20N4O2 and a molecular weight of 312.37 g/mol. It is also known as RSVA405. It is a potent and orally bioactive AMPK activator with an EC50 of 1 μM. RSVA405 inhibits mTOR by promoting CaMKKβ-dependent AMPK activation and promotes autophagy to increase Aβ degradation. It also inhibits STAT3 function, providing anti-inflammatory effects. The compound is an analog of resveratrol. Appearance: light yellow to yellow solid powder. This product is for research use only.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H20N4O2
Molecular Weight
312.37
Exact Mass
312.159
CAS #
140405-36-3
PubChem CID
135400298
Appearance
Light yellow to yellow solid powder
LogP
2.788
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
5
Rotatable Bond Count
6
Heavy Atom Count
23
Complexity
392
Defined Atom Stereocenter Count
0
SMILES
CCN(CC)C1=CC(=C(C=C1)/C=N/NC(=O)C2=CC=NC=C2)O
InChi Key
GWQPCBPAOAFXSJ-XDHOZWIPSA-N
InChi Code
InChI=1S/C17H20N4O2/c1-3-21(4-2)15-6-5-14(16(22)11-15)12-19-20-17(23)13-7-9-18-10-8-13/h5-12,22H,3-4H2,1-2H3,(H,20,23)/b19-12+
Chemical Name
N-[(E)-[4-(diethylamino)-2-hydroxyphenyl]methylideneamino]pyridine-4-carboxamide
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO : 125 mg/mL (400.17 mM)
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.2013 mL 16.0067 mL 32.0133 mL
5 mM 0.6403 mL 3.2013 mL 6.4027 mL
10 mM 0.3201 mL 1.6007 mL 3.2013 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.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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