Art. -Nr.: HY-13261

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A66

3 Cited Publications

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Based on 3 publication(s) in Google Scholar

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

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Reinheit: 99.73%
CAS. Nr.: 1166227-08-2
Formel: C₁₇H₂₃N₅O₂S₂
Molecular Weight:393.53

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

A66 Chemical Structure

CAS. Nr.: 1166227-08-2

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (3)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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)

Alle PI3K Isoform-spezifische Produkte anzeigen :

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	>10 μM Compound: 14, A66	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	[PMID: 26206504]
Rat1	IC₅₀	>10 μM Compound: 14, A66	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	[PMID: 26206504]
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]
Rat1	IC₅₀	0.2 μM Compound: 14, A66	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]

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.

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 C_max (8247 nM) of A66 S that is reached 30 min after dosing ensured that the AUC_0-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.

Chemical Information

CAS. Nr. 1166227-08-2
Appearance Solid
Molecular Weight 393.53
Formel C₁₇H₂₃N₅O₂S₂
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

EMBO Rep

Class IA PI3Ks regulate subcellular and functional dynamics of IDO1. [Abstract]

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

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.5411 mL

12.7055 mL

25.4110 mL

5 mM

0.5082 mL

2.5411 mL

5.0822 mL

10 mM

0.2541 mL

1.2706 mL

2.5411 mL

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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (6.35 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Protokoll

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].

MedChemExpress (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.

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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (283 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

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Targeted Diversity Library

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Anti-Colorectal Cancer Compound Library

Anti-Prostate Cancer Compound Library

Anti-Pulmonary Fibrosis Compound Library

Cancer Stem Cells Compound Library

Pain-Related Compound Library

Membrane Protein-targeted Compound Library

Highly Selective Inhibitors Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Anti-Fibrosis Compound Library

Anti-Brain Cancer Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Anti-Rheumatic Arthritis Compound Library

Posttranslational Modification Library

Lactylation Compound Library

Publications Citing Use of MedChemExpress (MCE) A66

Alle PI3K Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (3)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

A66 Related Classifications

HY-13261 Related Classifications