A-674563 hydrochloride

Name: A-674563 hydrochloride
Brand: MedChemExpress
SKU: HY-13254A
Rating: 5.0 (5 reviews)

Cat. No.: HY-13254A Purity: 99.86%: FAQs
Data Sheet SDS COA Handling Instructions

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A-674563 hydrochloride is a potent and selective Akt1 inhibitor with K_i of 11 nM.

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

A-674563 hydrochloride Chemical Structure

CAS No. : 2070009-66-2

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 154	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 154	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 60	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 140	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 220	In-stock	Estimated Time of Arrival: December 31
50 mg		Get quote
100 mg		Get quote

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Customer Review

Based on 5 publication(s) in Google Scholar

Other Forms of A-674563 hydrochloride:

A-674563 In-stock

4 Publications Citing Use of MCE A-674563 hydrochloride

: A-674563 hydrochloride purchased from MedChemExpress. Usage Cited in: Oncotarget. 2016 May 17;7(20):29131-42. [Abstract]; A674563 selectively inhibits FLT3-ITD. Inhibitory Effects of A674563 against auto-phosphorylation of FLT3 wt/mt kinases in the FLT3 wt/mt transformed BaF3 isogenic cell lines.

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Akt Akt1 Akt2 Akt3

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

A-674563 hydrochloride is a potent and selective Akt1 inhibitor with K_i of 11 nM.

IC₅₀ & Target^[1]

Akt1

11 nM (Ki)

PKA

16 nM (Ki)

CDK2

46 nM (Ki)

GSK3β

110 nM (Ki)

ERK2

260 nM (Ki)

PKCδ

360 nM (Ki)

RSK2

580 nM (Ki)

MAPK-AP2

1.1 μM (Ki)

PKCγ

1.2 μM (Ki)

Chk1

2.6 μM (Ki)

CK2

5.4 μM (Ki)

SRC

13 μM (Ki)

In Vitro

A-674563 slows proliferation of tumor cells with an EC₅₀ of 0.4 μM^[1]. A563 (0-10 µM) significantly decreases GSK3 and MDM2 phosphorylation in STS cells. A563 shows inhibitory effect on all STS cell lines, with IC₅₀ values at 48 hours ranging from 0.22±0.034 µM (SW684) to 0.35 ±0.06 µM (SKLMS1). A563 induces G2 cell cycle arrest and apoptosis in STS cells. A563 (1 µM/12 hr) upregulates the expression of GADD45A independent of p53^[2]. A-674563 (10-1000 nM) is anti-proliferative and cytotoxic in cultured human melanoma cells, induces melanoma cell apoptotic death, inhibited by caspase inhibitors, and inhibits melanoma cells via Akt-dependent and -independent mechanisms^[3]. A-674563 is cytotoxic and anti-proliferative when added to U937 and AmL progenitor cells, activates caspase-3/9 and apoptosis in U937 and AmL progenitor cells, and manipulates other signalings in AmL cells whiling blocking Akt^[4].

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

In Vivo

A-674563 (40 mg/kg/d, p.o.) shows no significant monotherapy activity, but the efficacy of the combination therapy (A-674563+paclitaxel) is significantly improved in the PC-3 prostate cancer xenograft model. A-674563 (20, 100 mg/kg) increases plasma insulin in an oral glucose tolerance test^[1]. A563 (20 mg/kg/bid; p.o.) exhibits slow tumor growth and a significant difference in tumor volume without significant weight loss of mice. A563-treated tumors express increased levels of GADD45α and decreased levels of PCNA (a nuclear marker for proliferation). Additionally, TUNEL assay staining levels (marker for apoptosis) increase in the A563-treated specimens^[2]. A-674563 (25, 100 mg/kg, lavage daily) potently inhibits A375 xenograft growth in mice^[3]. A-674563 (15, 40 mg/kg) injection inhibits U937 xenograft in vivo growth, and improves mice survival^[4].

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

Molecular Weight

394.90

Formula

C₂₂H₂₃ClN₄O

CAS No.

2070009-66-2

Appearance

Solid

Color

Light yellow to khaki

SMILES

N[C@@H](CC1=CC=CC=C1)COC2=CC(C3=CC4=C(C=C3)NN=C4C)=CN=C2.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility

In Vitro:

H₂O : 100 mg/mL (253.23 mM; Need ultrasonic)

DMSO : 50 mg/mL (126.61 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	2.5323 mL	12.6614 mL	25.3229 mL
5 mM	0.5065 mL	2.5323 mL	5.0646 mL
10 mM	0.2532 mL	1.2661 mL	2.5323 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, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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: ≥ 2.08 mg/mL (5.27 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (5.27 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (5.27 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 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 (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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: PBS
Solubility: 100 mg/mL (253.23 mM); Clear solution; Need ultrasonic and warming and heat to 60°C

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.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

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).

Purity & Documentation

Purity: 99.86%

Select Batch:

Data Sheet (280 KB) SDS (252 KB)

COA (247 KB) HNMR (290 KB) LCMS (96 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, 4(6), 977-986. [Content Brief]

[2]. Xu L, et al. Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells. Biochem Biophys Res Commun. 2016 Apr 15;472(4):662-8. [Content Brief]

[3]. Zhu QS, et al. Soft tissue sarcoma cells are highly sensitive to AKT blockade: a role for p53-independent up-regulation of GADD45 alpha. Cancer Res, 2008, 68(8), 2895-2903. [Content Brief]

[4]. Zou Y, et al. Pre-clinical assessment of A-674563 as an anti-melanoma agent. Biochem Biophys Res Commun. 2016 Aug 12;477(1):1-8. [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. Analysis is done using an fmax Fluorescence Microplate Reader, set at the excitation wavelength of 544 nm and emission wavelength of 595 nm. Data are analyzed using SOFTmax PRO software. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Immunocompromised male scid mice are at 6 to 8 weeks of age. 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. Gemcitabine and paclitaxel are added to the assay. 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, 4(6), 977-986. [Content Brief] [2]. Xu L, et al. Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells. Biochem Biophys Res Commun. 2016 Apr 15;472(4):662-8. [Content Brief] [3]. Zhu QS, et al. Soft tissue sarcoma cells are highly sensitive to AKT blockade: a role for p53-independent up-regulation of GADD45 alpha. Cancer Res, 2008, 68(8), 2895-2903. [Content Brief] [4]. Zou Y, et al. Pre-clinical assessment of A-674563 as an anti-melanoma agent. Biochem Biophys Res Commun. 2016 Aug 12;477(1):1-8. [Content Brief]

Complete Stock Solution Preparation Table

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

DMSO / H₂O	1 mM	2.5323 mL	12.6614 mL	25.3229 mL	63.3072 mL
	5 mM	0.5065 mL	2.5323 mL	5.0646 mL	12.6614 mL
	10 mM	0.2532 mL	1.2661 mL	2.5323 mL	6.3307 mL
	15 mM	0.1688 mL	0.8441 mL	1.6882 mL	4.2205 mL
	20 mM	0.1266 mL	0.6331 mL	1.2661 mL	3.1654 mL
	25 mM	0.1013 mL	0.5065 mL	1.0129 mL	2.5323 mL
	30 mM	0.0844 mL	0.4220 mL	0.8441 mL	2.1102 mL
	40 mM	0.0633 mL	0.3165 mL	0.6331 mL	1.5827 mL
	50 mM	0.0506 mL	0.2532 mL	0.5065 mL	1.2661 mL
	60 mM	0.0422 mL	0.2110 mL	0.4220 mL	1.0551 mL
	80 mM	0.0317 mL	0.1583 mL	0.3165 mL	0.7913 mL
	100 mM	0.0253 mL	0.1266 mL	0.2532 mL	0.6331 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.