A66
Based on 3 publication(s) in Google Scholar
A66 is a highly specific and selective p110α inhibitor with an IC50 of 32 nM.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.73%
- No. CAS: 1166227-08-2
- Fòrmula: C17H23N5O2S2
- Peso molecular:393.53
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) A66
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Actividad biológica
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p110α 32 nM (IC50) |
p110α E545K 30 nM (IC50) |
p110α H1047R 43 nM (IC50) |
p110γ 3480 nM (IC50) |
PI3K-C2β 462 nM (IC50) |
PI4Kβ 236 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Rat1 | IC50 |
>10 μM
Compound: A66
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Inhibition of N-terminal myristoylated human PI3Kbeta expressed in Rat1 cells assessed as inhibition of Akt phosphorylatuion at Ser473 by ELISA
Inhibition of N-terminal myristoylated human PI3Kbeta expressed in Rat1 cells assessed as inhibition of Akt phosphorylatuion at Ser473 by ELISA
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[PMID: 26199119] |
| Rat1 | IC50 |
>10 μM
Compound: A66
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Inhibition of N-terminal myristoylated human PI3Kgamma expressed in Rat1 cells assessed as inhibition of Akt phosphorylatuion at Ser473 by ELISA
Inhibition of N-terminal myristoylated human PI3Kgamma expressed in Rat1 cells assessed as inhibition of Akt phosphorylatuion at Ser473 by ELISA
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[PMID: 26199119] |
| Rat1 | IC50 |
>10 μM
Compound: 14, A66
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Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum
Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum
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[PMID: 26206504] |
| Rat1 | IC50 |
>10 μM
Compound: 14, A66
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Inhibition of PI3Kgamma in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum
Inhibition of PI3Kgamma in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum
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[PMID: 26206504] |
| Rat1 | IC50 |
0.2 μM
Compound: A66
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Inhibition of N-terminal myristoylated human PI3Kalpha expressed in Rat1 cells assessed as inhibition of Akt phosphorylatuion at Ser473 by ELISA
Inhibition of N-terminal myristoylated human PI3Kalpha expressed in Rat1 cells assessed as inhibition of Akt phosphorylatuion at Ser473 by ELISA
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[PMID: 26199119] |
| Rat1 | IC50 |
0.2 μM
Compound: 14, A66
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Inhibition of PI3Kalpha in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum
Inhibition of PI3Kalpha in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum
|
[PMID: 26206504] |
A66 is a potent inhibitor of the wild-type and oncogenic forms of p110α but not other class-I PI3K isoforms[1]. The p110α-specific inhibitor A66 (0.7 μM) induces a 75-80% reduction in focus formation by the highly transforming iSH2 mutants KS459delN, DKRMNS560del, and K379E. The p110α-specific inhibitor A66 reduced phosphorylation of Akt on T308 by all p85 mutants[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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No. CAS 1166227-08-2
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Appearance Solid
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Peso molecular 393.53
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Fòrmula C17H23N5O2S2
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Color Off-white to light yellow
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SMILES
CC(C)(C1=NC(C2=C(N=C(S2)NC(N3[C@@H](CCC3)C(N)=O)=O)C)=CS1)C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (3)
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Journal Impact Factor
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Most Recent
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EMBO Rep
2020 Dec 3;21(12):e49756. PMID: 33159421 -
Molecules
In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors Against Leishmania donovani and Trypanosoma brucei. [Abstract]2020 Apr 23;25(8):1980. PMID: 32340370 -
Cytokine
PI3K mediates tumor necrosis factor induced-necroptosis through initiating RIP1-RIP3-MLKL signaling pathway activation. [Abstract]2020 May;129:155046. PMID: 32114297
Solvente y solubilidad
DMSO : 50 mg/mL (127.06 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.35 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.35 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocolo
IC50 values are evaluated using the PI3K (human) HTRF Assay. p85α/p110δ is obtained from Invitrogen. All other isoforms are produced in-house by co-expressing full-length human p85α with the indicated human full-length catalytic subunit containing a histidine tag at the N-terminus to allow purification. The PI3Ks are titrated and used at a concentration between their EC65-EC80 values. PI3K activity in immunoprecipitates is assayed using an antibody to the N-SH2 (N-Src homology 2) domain of p85α. Assays for other lipid kinases and protein kinases are performed by the National Centre for Protein Kinase Profiling and Invitrogen Drug Discovery Services[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
Age-matched specific pathogen-free Rag1-/- or NIH-III mice are subcutaneously inoculated on the right flank with 5×106 U87MG, SK-OV-3 or HCT-116 cells in PBS. Tumour diameter as measured by electronic calipers is used to calculate tumour volume (mm3) based on the formula (L×w2)×π/6 (where L=longest tumour diameter and w=perpendicular diameter). A66 is administered in 20% 2-hydroxypropyl-β-cyclodextrin in water, whereas BEZ-235 is administered in 10% ethanol. Control mice are administered the A66 dosing vehicle alone. The drugs are dosed by intraperitoneal injection as the free base equivalent at a dosing volume of 10 mL/kg of body weight. For tumour pharmacodynamic studies, mice are administered a single dose of A66 or the control vehicle when tumors reached approximately 8-9 mm in diameter. Animals are killed 1 or 6 h after dosing and the tumors are removed, biopulverized and assayed for protein concentration. For antitumor efficacy studies, dosing began when tumors are well established, averaging approximately 7 mm in diameter. Doses are administered once daily (QD) or twice daily (BID) with injections separated by a minimum of approximately 8 h. Different dosing schedules are used for the three xenograft models depending on the rate of tumor growth and the body weight tolerance of control mice. Animals are dosed daily for 21 days or twice daily for 16 days (SK-OV-3), daily for 14 days (U87MG) and daily for 7 days (HCT-116). Animals are monitored daily for any signs of emerging toxicity and body weight is recorded. Mice are killed if they developed moderate signs of toxicity or if body weight loss exceeded 20% of starting weight. TGI (tumour growth inhibition) is calculated on the final day of dosing by determining the relative tumour size of drug-treated mice as a percentage of the average relative tumour size of control mice. The statistical significance of TGI values is determined by one-way ANOVA with Bonferroni multiple comparison analysis using GraphPad Prism 5.02.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureza y Documentación
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Ficha de datos (283 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Jamieson S, et al. A drug targeting only p110α can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types. Biochem J, 2011, 438(1), 53-62. [Content Brief]
[2]. Sun M, et al. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. Proc Natl Acad Sci U S A, 2010, 107(35), 15547-15552. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.5411 mL | 12.7055 mL | 25.4110 mL | 63.5276 mL |
| 5 mM | 0.5082 mL | 2.5411 mL | 5.0822 mL | 12.7055 mL | |
| 10 mM | 0.2541 mL | 1.2706 mL | 2.5411 mL | 6.3528 mL | |
| 15 mM | 0.1694 mL | 0.8470 mL | 1.6941 mL | 4.2352 mL | |
| 20 mM | 0.1271 mL | 0.6353 mL | 1.2706 mL | 3.1764 mL | |
| 25 mM | 0.1016 mL | 0.5082 mL | 1.0164 mL | 2.5411 mL | |
| 30 mM | 0.0847 mL | 0.4235 mL | 0.8470 mL | 2.1176 mL | |
| 40 mM | 0.0635 mL | 0.3176 mL | 0.6353 mL | 1.5882 mL | |
| 50 mM | 0.0508 mL | 0.2541 mL | 0.5082 mL | 1.2706 mL | |
| 60 mM | 0.0424 mL | 0.2118 mL | 0.4235 mL | 1.0588 mL | |
| 80 mM | 0.0318 mL | 0.1588 mL | 0.3176 mL | 0.7941 mL | |
| 100 mM | 0.0254 mL | 0.1271 mL | 0.2541 mL | 0.6353 mL |
A66 Related Classifications
HY-13261 Related Classifications
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