| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
QS11 (QS-11) is a novel and potent inhibitor of GTPase activating protein of ADP-ribosylation factor 1 (ARF-GAP1) [EC50 of 1.5 µM] with anticancer activity.
| Targets |
QS11 binds to ARF GTPase-activating protein 1 (ARFGAP1) and inhibits its enzymatic activity [1].
It acts as a Wnt synergistic agonist, activating the Wnt/β-catenin signaling pathway [1]. |
|---|---|
| ln Vitro |
It is possible that QS11 controls Wnt/β-catenin signaling via influencing protein trafficking because it binds to and inhibits the GTPase-activating protein ARFGAP1 [1]. In the presence of Wnt-3a conditioned media, QS11 (2.5 μM) can activate the Super(8X)TOPFlash reporter gene 200-fold, whereas Wnt-3a treatment alone can boost reporter gene activity by 40-fold [2]. QS11 has strong anti-HEK293 and human primary fibroblast activity (EC50=0.5 μM) and minimal cytotoxicity [2]. In vitro, QS11 efficiently inhibits the migration of human breast cancer cells that have spread [2].
QS11 (3a) at 10 µM and 20 µM inhibits ARFGAP1 enzymatic activity by 67% and 90%, respectively, in a biochemical assay using purified proteins [1]. The inactive analog QS11-NC (3b) shows no inhibitory activity against ARFGAP1 [1]. Structure-activity relationship studies identified analogs with modified potency: compound 8(2,r) shows approximately 2-fold improved EC50 in the TOPFlash reporter assay compared to QS11 [1]. |
| ln Vivo |
QS11 (10 μM, 10 nL) injected into Xenopus embryos synergizes with XWnt-8 RNA (0.5 pg) to induce axis duplication. In embryos treated with QS11 alone, 1.8% showed partial axis duplication; with XWnt-8 RNA alone, 20.5% showed partial axis duplication; with combination, 20.9% showed full and 30.2% showed partial axis duplication [2].
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| Enzyme Assay |
ARFGAP1 enzymatic activity was measured using myristoylated wild-type ARF1 and wild-type ARFGAP1. ARF1 was preloaded with radiolabeled [γ-32P]GTP in the presence of liposomes. GTP hydrolysis was initiated by mixing with full-length ARFGAP1 that had been pre-incubated with QS11 analogs for 10 minutes. The reaction was stopped by charcoal precipitation to scavenge protein and non-hydrolyzed GTP. Hydrolyzed 32P-labeled phosphate remained in the supernatant and was collected for scintillation counting. ARFGAP1 inhibition was tested at two compound concentrations (10 µM and 20 µM) with replicates [1].
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| Cell Assay |
Wnt/β-catenin signaling pathway activation was tested in HEK293 cells stably transfected with the TOPFlash reporter. Cells were stimulated with Wnt3A conditional medium for 24 hours before luciferase activity was measured using a luminescence kit [1].
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| Animal Protocol |
Xenopus embryos at the 16- to 32-cell stage were injected ventrally with 10 nL of QS11 (10 μM), 0.5 pg of XWnt-8 RNA, or a combination of both. Axis duplication was assessed after 2 days [2].
Xenopus embryos at the 16- to 32-cell stage were injected ventrally with 10 nL of QS11 (10 μM), 0.5 pg of XWnt-8 RNA, or a combination of both. Axis duplication was assessed after 2 days [2]. |
| Toxicity/Toxicokinetics |
QS11 shows little cytotoxicity toward HEK293 and human primary fibroblast cells at concentrations up to approximately 10 μM, which is its maximum solubility in culture media [2].
|
| References | |
| Additional Infomation |
(2S)-2-[[2-(2,3-dihydro-1H-indene-5-yloxy)-9-[(4-phenylphenyl)methyl]-6-purine]amino]-3-phenyl-1-propanol is a member of the biphenyl class of compounds.
QS11 is a small molecule previously reported to synergize with Wnt proteins to activate β-catenin signaling. Its mechanism was proposed to involve binding and inhibition of ARFGAP1. The present study confirms direct inhibition of ARFGAP1 by QS11 and suggests the presence of other potential cellular targets based on distinct SAR profiles between ARFGAP1 inhibition and Wnt synergy assays [1]. The structural differences between QS11 and its inactive analog QS11-NC highlight the critical role of the N9 substitution for activity [1]. |
| Molecular Formula |
C36H33N5O2
|
|---|---|
| Molecular Weight |
567.69
|
| Exact Mass |
567.263
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| CAS # |
944328-88-5
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| Related CAS # |
944328-88-5;
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| PubChem CID |
42623900
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
852.2±75.0 °C at 760 mmHg
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| Flash Point |
469.2±37.1 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.685
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| LogP |
6.67
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
43
|
| Complexity |
842
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C(C1C=CC(C2C=CC=CC=2)=CC=1)N1C=NC2C(=NC(=NC1=2)OC1C=CC2CCCC=2C=1)N[C@H](CO)CC1C=CC=CC=1
|
| InChi Key |
DOKZLKDGUQWMSX-HKBQPEDESA-N
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| InChi Code |
InChI=1S/C36H33N5O2/c42-23-31(20-25-8-3-1-4-9-25)38-34-33-35(40-36(39-34)43-32-19-18-28-12-7-13-30(28)21-32)41(24-37-33)22-26-14-16-29(17-15-26)27-10-5-2-6-11-27/h1-6,8-11,14-19,21,24,31,42H,7,12-13,20,22-23H2,(H,38,39,40)/t31-/m0/s1
|
| Chemical Name |
(2S)-2-[[2-(2,3-Dihydro-1H-inden-5-yloxy)-9-[(4-phenylphenyl)methyl]purin-6-yl]amino]-3-phenylpropan-1-ol
|
| Synonyms |
QS-11 QS11 QS 11
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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) |
DMSO : ≥ 100 mg/mL (~176.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7615 mL | 8.8076 mL | 17.6152 mL | |
| 5 mM | 0.3523 mL | 1.7615 mL | 3.5230 mL | |
| 10 mM | 0.1762 mL | 0.8808 mL | 1.7615 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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