Home PI3K/Akt/mTOR Akt inhibitor - CDK inhibitor - PKA inhibitor A-674563 HCl For research use only.

A-674563 HCl

A-674563 HCl is an Akt1 inhibitor with Ki of 11 nM in cell-free assays, modest potent to PKA and >30-fold selective for Akt1 over PKC.

A-674563 HCl Chemical Structure

A-674563 HCl Chemical Structure

CAS: 2070009-66-2

Selleck's A-674563 HCl has been cited by 28 Publications

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Purity & Quality Control

Batch: Purity: 99.66%
99.66

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation 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

Biological Activity

Description A-674563 HCl is an Akt1 inhibitor with Ki of 11 nM in cell-free assays, modest potent to PKA and >30-fold selective for Akt1 over PKC.
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
Akt1 [1]
(Cell-free assay)		 PKA [1]
(Cell-free assay)		 CDK2 [1]
(Cell-free assay)		 GSK-3β [1]
(Cell-free assay)		 ERK2 [1]
(Cell-free assay)		 Click to View More Targets
11 nM(Ki) 16 nM(Ki) 46 nM(Ki) 110 nM(Ki) 260 nM(Ki)
In vitro
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. [1] 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. [2]
Kinase Assay Akt 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 (Km = 40 μM), 5 μM peptide (Km = 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.
Cell Research Cell lines MiaPaCa-2 cells
Concentrations 0-30 μM
Incubation Time 48 hours
Method

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 M) 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 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 provided by the manufacturer.
In Vivo
In vivo

20 mg/kg A-674563 increases plasma insulin in an oral glucose tolerance test. A-674563 shows no significant monotherapy tumor inhibitory activity; the efficacy of the combination therapy is significantly improved compared to paclitaxel monotherapy. [1] 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. [2] 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. [3]
Animal Research Animal Models Fasted mice
Dosages 20 or 100 mg/kg
Administration A-674563 is administered 30 minutes before the 1 g/kg glucose challenge.

Chemical lnformation & Solubility

Molecular Weight 394.9 Formula

C22H22N4O.CIH
CAS No. 2070009-66-2 SDF --
Smiles CC1=C2C=C(C=CC2=NN1)C3=CC(=CN=C3)OCC(CC4=CC=CC=C4)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 72 mg/mL ( (182.32 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 72 mg/mL

Ethanol : 18 mg/mL


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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