2. PI3K/Akt/mTOR
  3. PI3K
  4. A66

A66 is a highly specific and selective p110α inhibitor with an IC50 of 32 nM.

For research use only. We do not sell to patients.

A66 Chemical Structure

A66 Chemical Structure

CAS No. : 1166227-08-2

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10 mM * 1 mL in DMSO
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10 mM * 1 mL in DMSO USD 106 In-stock
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10 mg USD 156 In-stock
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Customer Review

Based on 4 publication(s) in Google Scholar

A66 Related Antibodies

Top Publications Citing Use of Products

View All PI3K Isoform Specific Products:

View All Isoforms
PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

A66 is a highly specific and selective p110α inhibitor with an IC50 of 32 nM.

IC50 & Target[1]

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)

Cellular Effect
Cell Line Type Value Description References
Rat1 IC50
> 10 μM
Compound: A66
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
[PMID: 26199119]
Rat1 IC50
> 10 μM
Compound: A66
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
[PMID: 26199119]
Rat1 IC50
0.2 μM
Compound: A66
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
[PMID: 26199119]
In Vitro

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.

A66 Related Antibodies
In Vivo

The optimal dosing strategy for xenograft studies is determined by investigating the drug pharmacokinetics after a dose of 10 mg/kg of body weight by intraperitoneal injection in CD-1 mice. Despite a short half-life of only 0.42 h, the large Cmax (8247 nM) of A66 S that is reached 30 min after dosing ensured that the AUC0-inf (area under the curve from zero time to infinity) (6809 nM h) is similar to that of BEZ-235 (7333 nM h), which has a longer half-life of 2.73 h. Furthermore, the A66 on SK-OV-3 tumour tissue is tested using a single dose of 100 mg/kg of body weight to determine whether a long-lasting effect of the drug could be achieved on target tissues. These studies show that A66 causes a profound reduction in the phosphorylation of Akt/PKB and p70 S6 kinase, but not of ERK (extracellular-signal-regulated kinase), at both 1 and 6 h after dosing. Levels of A66 in plasma are determined to be 21.1±1.2 μM and 9.1±1.1 μM at 1 and 6 h after drug injection, whereas levels of A66 in the tumor are 22.7±2.1 μM and 16.0±1.3 μM at the same time points[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

393.53

Formula

C17H23N5O2S2
CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

CC(C)(C1=NC(C2=C(N=C(S2)NC(N3[C@@H](CCC3)C(N)=O)=O)C)=CS1)C
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.5411 mL 12.7055 mL 25.4110 mL
5 mM 0.5082 mL 2.5411 mL 5.0822 mL
View the 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.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation

Purity: 99.73%

SDS (393 KB)

COA (251 KB) LCMS (94 KB)

Handling Instructions (2659 KB)
References
Kinase Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

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.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

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
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A66 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

A661166227-08-2A 66A-66PI3KPhosphoinositide 3-kinaseInhibitorinhibitorinhibit

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