| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
Purity: =97.15%
| Targets |
Topoisomerase II
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| ln Vitro |
To investigate if such favorable changes in pO2 and CYP450 activating enzymes in tumors can strengthen AQ4N activation in vivo, we quantified the intratumoral AQ4 concentrations using the established HPLC‐MS/MS method (Figure 7F, and Figure S11, Supporting Information). Treatment without VP involved, such as c(RGDfK)‐ppGO/AQ4N and c(RGDfK)‐ppGO/AQ4N‐siHIF‐1α, only conferred extremely low AQ4 contents (<0.1 µg g−1) in tumors, which was in sharp contrast to any other treatments containing VP, demonstrating the importance of VP‐mediated VTP for hypoxia induction and AQ4N activation (Figure 7A,F). The positive effect of siHIF‐1α on AQ4N activation in tumors was also observed. At 48 h after irradiation, almost twofold AQ4 concentration was found in the tumors treated with the targeted trimodal nanosystem compared to that of control without siHIF‐1α (c(RGDfK)‐ppGO/VP‐AQ4N) (Figure 7F). Such effect of siHIF‐1α can be ascribed to its role of upregulating CYP1A1 and 2B6 prodrug‐activating enzymes (Figure 7B–E). It is also noticed that at 24 h after irradiation, no more AQ4 in tumors was obtained in the group of targeted trimodal nanosystem (Figure 7F), which may be ascribed to the moderate changes in the HIF‐1α inhibition and CYP450 upregulation in this duration (Figure S12, Supporting Information). [1]
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| Enzyme Assay |
AQ4N Activation into AQ4 after Treatment with Targeted Trimodal Nanosystem plus Irradiation: AQ4N can be reductively activated into AQ4 under hypoxic conditions by several cellular enzymes, such as CYP450. At 24 and 48 h after irradiation, three nude mice from each group (c(RGDfK)‐ppGO/AQ4N, c(RGDfK)‐ppGO/AQ4N‐siHIF‐1α, c(RGDfK)‐ppGO/VP‐AQ4N, ppGO/VP‐AQ4N‐siHIF‐1α, c(RGDfK)‐ppGO/VP‐AQ4N‐siHIF‐1α; VP 1 mg kg−1, AQ4N 5 mg kg−1, and siHIF‐1α 0.5 mg kg−1 in all groups with drug involved) were sacrificed, and tumors were excised and homogenized. Protein precipitation was produced with three volumes of acetonitrile for AQ4 sample preparation. Analyses were performed on an Agilent 6410 triple quadrupole mass spectrometer (Agilent Technologies, USA) equipped with electrospray ionization and an Agilent 1200 HPLC system (Agilent Technologies, USA). A Merck ZIC‐HILIC column (2.1 mm × 100 mm, 3.5 µm) was used for analyte separation. Isocratic elution with a mobile phase consisting of acetonitrile and water (60: 40, v/v, the aqueous phase contained 0.1% formic acid and 10 × 10−9 m ammonium formate, 0.3 mL min−1) was used for the separation. Two MRM transitions, AQ4 (m/z 413.2–72.2, fragmentor 140 eV, collision energy 20 eV) and IS (glycyrrhetic acid, m/z 471.5–177.1, fragmentor 160 eV, collision energy 30 eV) were monitored. Data processing of MS was performed on the MassHunter software package (VersionB.04.00, Agilent Technologies).[1]
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| Animal Protocol |
Quantification of Intratumoral AQ4:** Male BALB/c nude mice bearing PC-3 subcutaneous xenografts were treated with various nanoparticle formulations. At 24 and 48 hours after laser irradiation (690 nm, 50 mW cm⁻², 20 min), three mice from each group were sacrificed. Tumors were excised, weighed, and homogenized. Proteins were precipitated with three volumes of acetonitrile. AQ4 concentrations in the tumor homogenates were analyzed using an Agilent 6410 triple quadrupole mass spectrometer equipped with an Agilent 1200 HPLC system. Separation was performed on a Merck ZIC-HILIC column with isocratic elution using acetonitrile and water (60:40, v/v, aqueous phase contained 0.1% formic acid and 10 mM ammonium formate). Two MRM transitions were monitored: AQ4 (m/z 413.2 → 72.2) and internal standard (glycyrrhetic acid, m/z 471.5 → 177.1). Data were processed using MassHunter software [1].
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| References | |
| Additional Infomation |
AQ4 is the active metabolite of the hypoxia-activated prodrug AQ4N (banoxantrone) [1].
It is generated from AQ4N via enzymatic reduction by cytochrome P450 (CYP450) reductases (mainly CYP1A1 and CYP2B6) under hypoxic conditions [1].
AQ4 acts as a potent inhibitor of topoisomerase II and exerts cytotoxic effects on hypoxic tumor cells [1].
In the referenced study, AQ4 concentrations in tumors were measured by LC-MS/MS to assess AQ4N activation and its contribution to antitumor efficacy in combination with vascular-targeted photodynamic therapy and HIF-1α siRNA [1].
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| Molecular Formula |
C22H28N4O4
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|---|---|
| Molecular Weight |
412.48212
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| Exact Mass |
412.211
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| Elemental Analysis |
C, 64.06; H, 6.84; N, 13.58; O, 15.51
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| CAS # |
70476-63-0
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| PubChem CID |
135468
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| Appearance |
Solid powder
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| LogP |
1.966
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
30
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| Complexity |
562
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCNC1C2=C(C(=O)C3C(C2=O)=C(O)C=CC=3O)C(NCCN(C)C)=CC=1
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| InChi Key |
DBAMBJQJKDHEQX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H28N4O4/c1-25(2)11-9-23-13-5-6-14(24-10-12-26(3)4)18-17(13)21(29)19-15(27)7-8-16(28)20(19)22(18)30/h5-8,23-24,27-28H,9-12H2,1-4H3
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| Chemical Name |
1,4-bis[2-(dimethylamino)ethylamino]-5,8-dihydroxyanthracene-9,10-dione
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| Synonyms |
AQ4; AQ 4;
1,4-Bis((2-(dimethylamino)ethyl)amino)-5,8-dihydroxyanthracene-9,10-dione; 9,10-Anthracenedione, 1,4-bis((2-(dimethylamino)ethyl)amino)-5,8-dihydroxy-; DTXSID00220741; 1,4-Bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione; ...; 70476-63-0; AQ-4
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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 | 2.4244 mL | 12.1218 mL | 24.2436 mL | |
| 5 mM | 0.4849 mL | 2.4244 mL | 4.8487 mL | |
| 10 mM | 0.2424 mL | 1.2122 mL | 2.4244 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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