A-674563
Based on 5 publication(s) in Google Scholar
A-674563 is an orally active Akt1 inhibitor with a Ki of 11 nM.
For research use only. We do not sell to patients.
- Purity: 99.78%
- CAS No.: 552325-73-2
- Formula: C22H22N4O
- Molecular Weight:358.44
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Protocol
- Purity & Documentation
- References
-
Help & FAQs
-
Kinase Inhibitor Library
HY-L009
-
PI3K/Akt/mTOR Compound Library
HY-L015
-
Stem Cell Signaling Compound Library
HY-L017
-
Anti-Cancer Compound Library
HY-L025
-
Autophagy Compound Library
HY-L029
-
Anti-Aging Compound Library
HY-L034
-
Differentiation Inducing Compound Library
HY-L038
-
Oxygen Sensing Compound Library
HY-L045
-
Glycolysis Compound Library
HY-L058
-
Cytoskeleton Compound Library
HY-L060
-
Glutamine Metabolism Compound Library
HY-L064
-
Anti-Breast Cancer Compound Library
HY-L074
-
Anti-Lung Cancer Compound Library
HY-L075
-
Anti-Pancreatic Cancer Compound Library
HY-L077
-
Anti-Blood Cancer Compound Library
HY-L079
-
Anti-Cancer Metabolism Compound Library
HY-L083
-
Anti-Obesity Compound Library
HY-L087
-
Angiogenesis-Related Compound Library
HY-L088
-
Glucose Metabolism Compound Library
HY-L092
-
Targeted Diversity Library
HY-L099
-
Anti-Liver Cancer Compound Library
HY-L101
-
Anti-Colorectal Cancer Compound Library
HY-L103
-
Anti-Prostate Cancer Compound Library
HY-L124
-
Anti-Pulmonary Fibrosis Compound Library
HY-L125
-
Cancer Stem Cells Compound Library
HY-L135
-
Heterocyclic Compound Library
HY-L138
-
Pain-Related Compound Library
HY-L139
-
Highly Selective Inhibitors Library
HY-L158
-
Serine/Threonine Kinase Inhibitor Library
HY-L164
-
Anti-Hematopathy Compound Library
HY-L171
-
Anti-Ovarian Cancer Compound Library
HY-L173
-
Multi-Target Compound Library
HY-L176
-
Bioactive Compound Library Max
HY-L181
-
MCE Bioactive Compound Library
HY-L001V
-
Bioactive Compound Library
HY-L001
-
Anti-Gastric Cancer Compound Library
HY-L184
-
Anti-Fibrosis Compound Library
HY-L185
-
Protein Kinase Compound Library
HY-L196
-
Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
-
Cell Proliferation Compound Library
HY-L201
-
High-Throughput Bioactive Compound Library
HY-L205
-
Posttranslational Modification Library
HY-L226
-
Lactylation Compound Library
HY-L249
Publications Citing Use of MedChemExpress (MCE) A-674563
More
Customer Validation & Images
-
WB
Biological Activity
|
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) |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MIA PaCa-2 | EC50 |
0.4 μM
Compound: 11g
|
Antiproliferative activity against human MiaPaCa2 cell line
Antiproliferative activity against human MiaPaCa2 cell line
|
[PMID: 16678413] |
| MOLM-13 | EC50 |
0.17 μM
Compound: 17; A674563
|
Cytotoxicity against human MOLM13 cells
Cytotoxicity against human MOLM13 cells
|
[PMID: 31207462] |
| MOLM-14 | EC50 |
0.06 μM
Compound: 17; A674563
|
Cytotoxicity against human MOLM14 cells
Cytotoxicity against human MOLM14 cells
|
[PMID: 31207462] |
| MV4-11 | EC50 |
0.092 μM
Compound: 17; A674563
|
Cytotoxicity against human MV4-11 cells
Cytotoxicity against human MV4-11 cells
|
[PMID: 31207462] |
| Sf9 | IC50 |
>100 μM
Compound: A674563
|
Inhibition of Akt1 (1 to 480) expressed in Sf9 cells by indirect affinity mass spectrometry assay
Inhibition of Akt1 (1 to 480) expressed in Sf9 cells by indirect affinity mass spectrometry assay
|
[PMID: 22533986] |
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 μM (SW684) to 0.35 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.
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.
Chemical Information
-
CAS No. 552325-73-2
-
Appearance Solid
-
Molecular Weight 358.44
-
Formula C22H22N4O
-
Color White to yellow
-
SMILES
N[C@@H](CC1=CC=CC=C1)COC2=CC(C3=CC4=C(C=C3)NN=C4C)=CN=C2
-
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
Publications (5)
-
Journal Impact Factor
-
Most Recent
-
Cell Commun Signal
CDO1 phosphorylation is required for IL-6-induced tumor cell proliferation through governing cysteine availability. [Abstract]2025 Apr 23;23(1):194. PMID: 40269955 -
Aging
Intracellular and extracellular S100A9 trigger epithelial-mesenchymal transition and promote the invasive phenotype of pituitary adenoma through activation of AKT1. [Abstract]2020 Nov 17;12(22):23114-23128. PMID: 33203795 -
Cell Signal
Repurposing a plant alkaloid homoharringtonine targets insulinoma associated-1 in N-Myc-activated neuroblastoma. [Abstract]2023 Sep:109:110753. PMID: 37301315 -
J Proteome Res
2018 Oct 5;17(10):3360-3369. PMID: 30156101 -
Oncotarget
Dual inhibition of AKT/FLT3-ITD by A674563 overcomes FLT3 ligand-induced drug resistance in FLT3-ITD positive AML. [Abstract]2016 May 17;7(20):29131-42. PMID: 27074558
A-674563 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.
Solvent & Solubility
DMSO : 83.33 mg/mL (232.48 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 90% (20% SBE-β-CD in Saline)
Solubility: 5.75 mg/mL (16.04 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 5.75 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (57.5 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.80 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.
Please enter the basic information of animal 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
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.
Protocol
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
-
Data Sheet (279 KB)
-
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Portuguese - PT (396 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]. Wang A, et al. Dual inhibition of AKT/FLT3-ITD by A674563 overcomes FLT3 ligand-induced drug resistance in FLT3-ITD positive AML. Oncotarget. 2016 May 17;7(20):29131-42. [Content Brief]
[5]. 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
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 | 2.7899 mL | 13.9493 mL | 27.8987 mL | 69.7467 mL |
| 5 mM | 0.5580 mL | 2.7899 mL | 5.5797 mL | 13.9493 mL | |
| 10 mM | 0.2790 mL | 1.3949 mL | 2.7899 mL | 6.9747 mL | |
| 15 mM | 0.1860 mL | 0.9300 mL | 1.8599 mL | 4.6498 mL | |
| 20 mM | 0.1395 mL | 0.6975 mL | 1.3949 mL | 3.4873 mL | |
| 25 mM | 0.1116 mL | 0.5580 mL | 1.1159 mL | 2.7899 mL | |
| 30 mM | 0.0930 mL | 0.4650 mL | 0.9300 mL | 2.3249 mL | |
| 40 mM | 0.0697 mL | 0.3487 mL | 0.6975 mL | 1.7437 mL | |
| 50 mM | 0.0558 mL | 0.2790 mL | 0.5580 mL | 1.3949 mL | |
| 60 mM | 0.0465 mL | 0.2325 mL | 0.4650 mL | 1.1624 mL | |
| 80 mM | 0.0349 mL | 0.1744 mL | 0.3487 mL | 0.8718 mL | |
| 100 mM | 0.0279 mL | 0.1395 mL | 0.2790 mL | 0.6975 mL |
Powered by Bioz