A-443654

Name: A-443654
Brand: MedChemExpress
SKU: HY-10425
Rating: 5.0 (13 reviews)

Cat. No.: HY-10425 Purity: 99.71%: FAQs
Data Sheet SDS COA Handling Instructions

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A-443654 is a pan-Akt inhibitor and has equal potency against Akt1, Akt2, or Akt3 within cells (K_i=160 pM).

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

A-443654 Chemical Structure

CAS No. : 552325-16-3

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 275	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 275	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 250	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 390	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 720	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 1100	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1650	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 13 publication(s) in Google Scholar

10 Publications Citing Use of MCE A-443654

IHC

: A-443654 purchased from MedChemExpress. Usage Cited in: CNS Neurosci Ther. 2018 Jun;24(6):495-507. [Abstract]; The MPP/PHTPP-and G15-induced decreases in p-AKT, AKT, and rictor expression are differently affected by mTORC2 activation with A-443654 in the adult female hippocampus.

: A-443654 purchased from MedChemExpress. Usage Cited in: CNS Neurosci Ther. 2018 Jun;24(6):495-507. [Abstract]; Immunohistochemistry results show that the MPP/PHTPP- and G15-induced dramatic decrease in profilin-1 expression is significantly reversed by A-443654.

: A-443654 purchased from MedChemExpress. Usage Cited in: J Steroid Biochem Mol Biol. 2017 Nov;174:96-113. [Abstract]; A443654 rescues the methylphenolpyrazole (MPP) + PHTPP-induced downregulation of p-AKT.

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View All Isoforms

Akt Akt1 Akt2 Akt3

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

A-443654 is a pan-Akt inhibitor and has equal potency against Akt1, Akt2, or Akt3 within cells (K_i=160 pM)^[1].

IC₅₀ & Target

Akt1

160 pM (Ki)

Akt2

160 pM (Ki)

Akt3

160 pM (Ki)

PKA

6.3 nM (Ki)

RSK2

11 nM (Ki)

PKCγ

24 nM (Ki)

CDK2

24 nM (Ki)

PKCδ

33 nM (Ki)

GSK3β

41 nM (Ki)

ERK2

340 nM (Ki)

cKIT

1.2 μM (Ki)

Chk1

2.3 μM (Ki)

CK2

2.4 μM (Ki)

SRC

2.6 μM (Ki)

KDR

3.1 μM (Ki)

MAPK-AP2

3.3 μM (Ki)

Flt1

3.6 μM (Ki)

Cellular Effect

Cell Line	Type	Value	Description	References
HEK-293T	IC₅₀	2.5 nM Compound: A-443654	Inhibition of myristoylated wild type AKT1 expressed in HEK293T cells by in vitro immunoprecipitation kinase assay Inhibition of myristoylated wild type AKT1 expressed in HEK293T cells by in vitro immunoprecipitation kinase assay	[PMID: 19465931]
HEK-293T	IC₅₀	30 nM Compound: A-443654	Inhibition of myristoylated wild type AKT2 expressed in HEK293T cells by in vitro immunoprecipitation kinase assay Inhibition of myristoylated wild type AKT2 expressed in HEK293T cells by in vitro immunoprecipitation kinase assay	[PMID: 19465931]
HEK-293T	IC₅₀	51 nM Compound: A-443654	Inhibition of myristoylated wild type AKT3 expressed in HEK293T cells by in vitro immunoprecipitation kinase assay Inhibition of myristoylated wild type AKT3 expressed in HEK293T cells by in vitro immunoprecipitation kinase assay	[PMID: 19465931]

In Vitro

A-443654 exhibits a K_i of 160 pM, a 30,000-fold improvement in potency versus the initial lead molecule. A-443654 is 40-fold selective for Akt over PKA. A-443654 inhibits Akt1, Akt2, or Akt3 equally within cells. A-443654 reduces the P-GSK3 in a dose-responsive manner in all three cell lines. A-443654 inhibits the proliferation of tumor cells with EC₅₀ of 0.1 μM^[1]. A-443654-induced morphological changes occur very rapidly (within 2 to 4 h) in both 10A and 10CA1a cells, with 10CA1a cells more sensitive to A-443654 than the 10A cells. A-443654 alone at 2 μM causes the 10CA1a cells, but not the 10A cells, to detach from the plate after 12 h, whereas 1 μM of A-443654 causes 10CA1a cells to detach from the plate after 12 h. FACScan Analysis of rapamycin and A-443654 effects on DNA content in 10A and 10CA1a cells. In contrast, A-443654 at 2 and 5 μM decreases Bcl-2 levels by 30 to 40% in the 10CA1a cells at 8h. The combination of rapamycin with 2 or 5 μM A-443654, however, markedly decreases Bcl-2 protein levels by appr 40 to 50% in the 10A cells and by appr 70% in the 10CA1a cells, respectively^[2]. A-443654 demonstrates the greatest selective effect on the mutant cells compared to the WT cells with greater than 3.5 fold relative growth inhibition of the mutant cells^[3].

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

In Vivo

A-443654 (7.5 mg/kg/d, s.c.) inhibits tumor growth in the 3T3-Akt1 flank tumor model. A-443654 (50 mg/kg, s.c.) induces apoptosis in 3T3-Akt1 flank tumors. A-443654 (30 mg/kg, s.c.) leads to increased levels of phosphorylated Akt1 in MiaPaCa-2 tumors^[1].

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

Molecular Weight

397.47

Formula

C₂₄H₂₃N₅O

CAS No.

552325-16-3

Appearance

Solid

Color

White to off-white

SMILES

N[C@H](COC1=CN=CC(C2=CC3=C(NN=C3C)C=C2)=C1)CC4=CNC5=CC=CC=C54

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 : ≥ 100 mg/mL (251.59 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.5159 mL	12.5796 mL	25.1591 mL
5 mM	0.5032 mL	2.5159 mL	5.0318 mL
10 mM	0.2516 mL	1.2580 mL	2.5159 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)

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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 (6.29 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 (6.29 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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.29 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

mg/kg

Animal weight
(per animal)

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: 99.71%

Select Batch:

Data Sheet (280 KB) SDS (251 KB)

COA (247 KB) LCMS (105 KB)

Handling Instructions (2659 KB)

References

[1]. Luo Y, et al. Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol Cancer Ther. 2005 Jun;4(6):977-86. [Content Brief]

[2]. Zheng J, et al. Rapamycin sensitizes Akt inhibition in malignant human breast epithelial cells. Cancer Lett. 2010 Oct 1;296(1):74-87. [Content Brief]

[3]. Gallia GL, et al. Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells. Mol Cancer Ther. 2009 Feb;8(2):386-93. [Content Brief]

[4]. Zhao Y, et al. Estrogen receptor alpha and beta regulate actin polymerization and spatial memory through an SRC-1/mTORC2-dependent pathway in the hippocampus of female mice. J Steroid Biochem Mol Biol. 2017 Nov;174:96-113. [Content Brief]

Cell Assay ^[1]	The cells on 96-well plates are gently washed with 200 μL of PBS. Alamar Blue reagent is diluted 1:10 in normal growth media. The diluted Alamar Blue reagent (100 μL) is added to each well on the 96-well plates and incubated until the reaction is complete as per manufacturer's instructions. Analysis is done using an fmaxFluorescence Microplate Reader, set at the excitation wavelength of 544 nm and emission wavelength of 595 nm. Data are analyzed using SOFTmax PRO software provided by the manufacturer. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Immunocompromised male scid mice are 6 to 8 weeks of age. The 3T3-Akt1 cell line is developed and characterized in our laboratory. The 1×10⁶ 3T3-Akt1 or 2×10⁶ MiaPaCa-2 and PC-3 cells in 50% Matrigel are inoculated s.c. into the flank. For early treatment studies, mice are randomLy assigned to treatment groups and therapy is initiated the day after inoculation. Ten animals are assigned to each group, including controls. For established tumor studies, tumors are allowed to reach a designated size and mice are assigned to treatment groups of equal tumor size (n=10 mice per group). Tumor size is evaluated by twice weekly measurements with digital calipers. Tumor volume is estimated using the formula: V=L×W²/2. A-443654 is given s.c. in a vehicle of 0.2% HPMC. A-674563 is given orally in a vehicle of 5% dextrose. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Luo Y, et al. Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol Cancer Ther. 2005 Jun;4(6):977-86. [Content Brief] [2]. Zheng J, et al. Rapamycin sensitizes Akt inhibition in malignant human breast epithelial cells. Cancer Lett. 2010 Oct 1;296(1):74-87. [Content Brief] [3]. Gallia GL, et al. Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells. Mol Cancer Ther. 2009 Feb;8(2):386-93. [Content Brief] [4]. Zhao Y, et al. Estrogen receptor alpha and beta regulate actin polymerization and spatial memory through an SRC-1/mTORC2-dependent pathway in the hippocampus of female mice. J Steroid Biochem Mol Biol. 2017 Nov;174:96-113. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.5159 mL	12.5796 mL	25.1591 mL	62.8978 mL
	5 mM	0.5032 mL	2.5159 mL	5.0318 mL	12.5796 mL
	10 mM	0.2516 mL	1.2580 mL	2.5159 mL	6.2898 mL
	15 mM	0.1677 mL	0.8386 mL	1.6773 mL	4.1932 mL
	20 mM	0.1258 mL	0.6290 mL	1.2580 mL	3.1449 mL
	25 mM	0.1006 mL	0.5032 mL	1.0064 mL	2.5159 mL
	30 mM	0.0839 mL	0.4193 mL	0.8386 mL	2.0966 mL
	40 mM	0.0629 mL	0.3145 mL	0.6290 mL	1.5724 mL
	50 mM	0.0503 mL	0.2516 mL	0.5032 mL	1.2580 mL
	60 mM	0.0419 mL	0.2097 mL	0.4193 mL	1.0483 mL
	80 mM	0.0314 mL	0.1572 mL	0.3145 mL	0.7862 mL
	100 mM	0.0252 mL	0.1258 mL	0.2516 mL	0.6290 mL

A-443654 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:

A-443654552325-16-3A443654A 443654AktPKBProtein kinase BInhibitorinhibitorinhibit

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A-443654

Customer Review

A-443654 Related Antibodies

10 Publications Citing Use of MCE A-443654

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•Related Screening Libraries:

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View All Akt Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

A-443654 Related Antibodies

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Complete Stock Solution Preparation Table

A-443654 Related Classifications

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