Name: A-674563 HCl
Brand: Selleck Chemicals
SKU: S2670
Availability: InStock
Rating: 5 (29 reviews)

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Quality Control

Batch: Purity: 99.66%

99.66

Related Targets	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Other Akt Inhibitors	SC79 Ipatasertib (GDC-0068) MK-2206 Dihydrochloride Perifosine AZD5363 (Capivasertib) GSK690693 Triciribine (API-2) CCT128930 Afuresertib (GSK2110183) AT7867

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Activity Description	PMID
MiaPaCa2 cell	Proliferation assay	Antiproliferative activity against human MiaPaCa2 cell line, EC50=0.4 μM	16678413
MIA PaCa cells	Cytotoxic assay	Cytotoxicity against human MIA PaCa cells by MTT assay, EC50=0.64 μM	17523610
MOLM14	Cytotoxicity assay	Cytotoxicity against human MOLM14 cells, EC50=0.06μM.	31207462
MV4-11	Cytotoxicity assay	Cytotoxicity against human MV4-11 cells, EC50=0.092μM.	31207462
MOLM13	Cytotoxicity assay	Cytotoxicity against human MOLM13 cells, EC50=0.17μM.	31207462
KB-3-1	Function assay	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	31515284
TC32	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	31515284
DAOY	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	31515284
SJ-GBM2	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
Saos-2	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
RD	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
NB1643	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
BT-37	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
fibroblast cells	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells	29435139
Rh18	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 72 mg/mL (182.32 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 72 mg/mL

Ethanol : 18 mg/mL

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	Saline Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (75.97mM)	Taking the 1 mL working solution as an example, add 30 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

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%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	394.9	Formula	C₂₂H₂₂N₄O.CIH	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	2070009-66-2	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=C2C=C(C=CC2=NN1)C3=CC(=CN=C3)OCC(CC4=CC=CC=C4)N

Mechanism of Action

Features	Orally bioavailable compound (achieved by replacing indole of A-443654 with phenyl moiety) and somewhat less selective for Akt over PKA than A-443654.
Targets/IC₅₀/Ki	Akt1 (Cell-free assay) 11 nM(Ki) PKA (Cell-free assay) 16 nM(Ki) CDK2 (Cell-free assay) 46 nM(Ki) GSK-3β (Cell-free assay) 110 nM(Ki) ERK2 (Cell-free assay) 260 nM(Ki) PKCδ (Cell-free assay) 360 nM(Ki) RSK2 (Cell-free assay) 580 nM(Ki)
In vitro	A-674563 HCl is achieved from A-443654 by replacing the indole with a phenyl moiety and getting oral activity. A-674563 slows proliferation of tumor cells with EC50 of 0.4 μM. A-674563 does not inhibit Akt phosphorylation per se, but blocks the phosphorylation of Akt downstream targets in a dose-dependent manner. A-674563 induced Akt blockade results in decreased STS cell downstream target phosphorylation and tumor cell growth inhibiton. A-674563 induces G2 cell cycle arrest and apoptosis in STS cells.
Kinase Assay	Akt Kinase Assay
Kinase Assay	The kinase assay uses His-Akt1 and a biotinylated mouse Bad peptide as substrate. The kinase assay is carried out at room temperature for 30 minutes in 50 μL of reaction buffer [20 mM HEPES, pH 7.5, 10 mM MgCl₂, 0.1% (w/v) Triton X-100, 5 μM ATP (K_m = 40 μM), 5 μM peptide (K_m = 15 μM), 1 mM DTT, 60 ng of Akt1, and 0.5 μCi of [γ-³³P]ATP] in the presence of different concentrations of A-674563. Each reaction is stopped by adding 50 μL of termination buffer (0.1 M EDTA, pH 8.0, and 4 M NaCl). The biotinylated Bad peptides are immobilized on streptavidin-coated FLASH plates. Afterbeing washed with PBS-Tween 20 (0.05%), the ³³P phosphopeptide captured on the FLASH plates is measured with a TopCount Packard Instruments γ counter.
In vivo	A-674563 shows no significant monotherapy tumor inhibitory activity; the efficacy of the combination therapy is significantly improved compared to monotherapy. A674563-treated (20 mg/kg/bid, p.o.) mice exhibits slower tumor growth and more than 50% decrease in the tumor volume at the termination of the study compared with that in control group. A-674563 is identified to have drastically improved PK profile with oral bioavailability of 67% in mouse, but is 70-fold less active than A-443654.
References	[1] https://pubmed.ncbi.nlm.nih.gov/15956255/ [2] https://pubmed.ncbi.nlm.nih.gov/20582381/ [3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932704/

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A-674563 HCl Akt inhibitor

Chemical Structure

Molecular Weight: 394.9