| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Sirtuin-3 (SIRT3) (KD: 2.756 in binding assay) [1]
|
|---|---|
| ln Vitro |
- SIRT3 activation: 2-APQC potently activated SIRT3 deacetylase activity in a dose-dependent manner, with a KD value of 2.756 μM. The activation was confirmed by increased deacetylation of mitochondrial proteins, including pyruvate dehydrogenase E1 subunit α (PDHA1) and manganese superoxide dismutase (SOD2) [1].
- Mitochondrial homeostasis regulation: In H9c2 cardiomyoblasts, 2-APQC (1–10 μM) significantly reduced reactive oxygen species (ROS) levels, restored mitochondrial membrane potential, and increased ATP production under oxidative stress conditions. These effects were abrogated in SIRT3-knockdown cells, confirming SIRT3 dependency [1]. - Pathway inhibition: 2-APQC (5 μM) suppressed the phosphorylation of mTOR (Ser2448), p70S6K (Thr389), JNK (Thr183/Tyr185), and Smad3 (Ser423/425) in ISO-induced hypertrophic cardiomyocytes, indicating inhibition of pro-hypertrophic signaling pathways [1]. |
| ln Vivo |
- Myocardial hypertrophy and fibrosis alleviation: In ISO-induced rat models, 2-APQC (10 mg/kg, intraperitoneal injection daily for 14 days) significantly reduced heart weight/body weight ratio (from 4.8 ± 0.3 mg/g to 3.5 ± 0.2 mg/g), cardiomyocyte cross-sectional area (by 32%), and collagen deposition (as assessed by Masson’s trichrome staining). These effects were abolished in SIRT3 knockout mice [1].
- Mitochondrial protection: 2-APQC treatment restored mitochondrial cristae structure, reduced mitochondrial ROS generation, and increased SOD2 activity in the hearts of ISO-treated rats. RNA-seq analysis revealed upregulation of PYCR1 and downregulation of p38MAPK signaling, suggesting a role for mitochondrial proline metabolism in cardioprotection [1]. |
| Enzyme Assay |
SIRT3 deacetylase activity assay: Recombinant human SIRT3 was incubated with a fluorogenic substrate (Fluor de Lys™) and NAD+ in a buffer containing 50 mM Tris-HCl (pH 8.0), 137 mM NaCl, and 2.7 mM KCl. 2-APQC (0.1–10 μM) was added, and fluorescence intensity was measured at excitation/emission wavelengths of 360/460 nm. The KD value was determined by fitting dose-response curves to a binding model [1].
|
| Cell Assay |
- Cardiomyocyte hypertrophy assay: Primary neonatal rat ventricular cardiomyocytes were treated with ISO (10 μM) to induce hypertrophy, followed by 2-APQC (1–10 μM) for 48 hours. Cell surface area was measured using wheat germ agglutinin staining, and ANP/BNP mRNA levels were quantified by qPCR. 2-APQC significantly attenuated ISO-induced hypertrophy in a dose-dependent manner [1].
- Apoptosis assay: H9c2 cells subjected to hypoxia-reoxygenation injury were treated with 2-APQC (5 μM). Annexin V/PI staining and caspase-3 activity assays showed reduced apoptotic cell death, accompanied by increased Bcl-2/Bax ratio and decreased cleaved caspase-3 levels [1]. |
| Animal Protocol |
- ISO-induced hypertrophy model: Male Sprague-Dawley rats (200–250 g) received subcutaneous ISO injections (5 mg/kg/day for 7 days) to induce myocardial hypertrophy. 2-APQC (10 mg/kg) was dissolved in 0.5% carboxymethylcellulose and administered intraperitoneally once daily for 14 days. Hearts were harvested for histological and biochemical analyses [1].
- SIRT3 knockout mice: SIRT3-/- mice and wild-type littermates were treated with 2-APQC (10 mg/kg, intraperitoneal) during ISO challenge. Cardiac function was assessed by echocardiography, and tissue samples were analyzed for fibrosis and mitochondrial markers [1]. |
| References | |
| Additional Infomation |
- Mechanism of action: 2-APQC binds to the NAD+ binding pocket (L pocket) of SIRT3, stabilizing the enzyme's active conformation and enhancing its deacetylase activity. This leads to PYCR1-mediated activation of proline metabolism, inhibition of the ROS-p38MAPK signaling pathway, and inhibition of necrotizing apoptosis via the AMPK-Parkin pathway [1]. - Therapeutic potential: 2-APQC represents a novel class of SIRT3-targeting activators that have shown efficacy in preclinical models of heart failure, providing a potential strategy for mitochondrial protective therapy [1].
|
| Molecular Formula |
C23H24FN5O
|
|---|---|
| Molecular Weight |
405.47
|
| Elemental Analysis |
C, 68.13; H, 5.97; F, 4.69; N, 17.27; O, 3.95
|
| CAS # |
500271-63-6
|
| Appearance |
White to off-white solid powder
|
| SMILES |
FC1C=CC(=CC=1)CN1C(=C(C(NCCCCC)=O)C2C1=NC1C=CC=CC=1N=2)N
|
| Synonyms |
2-APQC; 2APQC; 2-amino-1-(4-fluorobenzyl)-N-pentyl-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide; 500271-63-6; orb2646181; 2-amino-1-[(4-fluorophenyl)methyl]-N-pentylpyrrolo[3,2-b]quinoxaline-3-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 (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 | 2.4663 mL | 12.3314 mL | 24.6627 mL | |
| 5 mM | 0.4933 mL | 2.4663 mL | 4.9325 mL | |
| 10 mM | 0.2466 mL | 1.2331 mL | 2.4663 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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