A-674563 HCl (552325-73-2(free base))

SKU: orb1302854

Description

Research Area

Cell Biology, Epigenetics & Chromatin, Signal Transduction

Images & Validation

−

Key Properties

−

CAS Number	2070009-66-2
MW	394.9
Purity	99.69%
Formula	C₂₂H₂₃ClN₄O
SMILES	CC=1C=2C(=CC=C(C2)C=3C=C(OC[C@H](CC4=CC=CC=C4)N)C=NC3)NN1.Cl
Target	PKA,PKC,ERK,CDK,Akt
Solubility	DMSO:>30 mg/mL

Bioactivity

−

Target IC50	CDK2:46 nM (Ki)\|PKCδ:360 nM (Ki)\|ERK2:260 nM (Ki)\|PKA:16 nM (Ki)\|GSK-3β:110 nM (Ki)\|Akt1:11 nM (Ki)
In Vivo	In the PC-3 prostate cancer xenograft model, A-674563 (40 mg/kg/d, p.o.) has no marked monotherapy activity, but the efficacy of the combination therapy (A-674563+paclitaxel) is significantly improved. In an oral glucose tolerance test, A-674563 (20, 100 mg/kg) can increase plasma insulin. 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. A-674563 (25, 100 mg/kg, lavage daily) effectively inhibits A375 xenograft growth in mice. A-674563 (15, 40 mg/kg) injection inhibits U937 xenograft in vivo growth and improves mice survival. Read more...
In Vitro	A-674563 reduces phosphorylation of Akt downstream targets in cells and slows proliferation of tumor cells in vitro (EC50: 0.4 μM) . A563 (0-10 μM) markedly 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 to 0.35 μM. A563 induces G2 cell cycle arrest and apoptosis in STS cells. A563 (1 μM/12 hr) upregulates the expression of GADD45A independent of p53. 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. A-674563 is cytotoxic and anti-proliferative when added to U937 and AmL progenitor cells activate caspase-3/9 and apoptosis in U937 and AmL progenitor cells and manipulate other signalings in AmL cells whiling blocking Akt. Read more...
Cell Research	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. The analysis is done using a fmax Fluorescence Microplate Reader, set at the excitation wavelength of 544 nm and the emission wavelength of 595 nm. Data are analyzed using SOFTmax PRO software. Read more...
Animal Research	A-674563 is formulated in 5% dextrose.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. Read more...

Storage & Handling

−

Storage	Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice/Shipping at ambient temperature.
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

Alternative Names

−

Akt1, A674563 HCl (552325732(free base)), A-674563 HCl (552325-73-2(free base)), A 674563 HCl (552325 73 2(free base)), CDK2, ERK2, PKA, PKCδ

Quality Guarantee

Explore bioreagents carefree to elevate your research. All our products are rigorously tested for performance. If a product does not perform as described on its datasheet, our scientific support team will provide expert troubleshooting, a prompt replacement, or a refund. For full details, please see our Terms & Conditions and Buying Guide. Contact us at support@biorbyt.com.

Compound Identifiers

PubChem CID

73357690 ↗

Key Properties

−

No computed properties available.

Documents Download

Datasheet

Product Information

Download

Request a Document

Protocol Information

Find More Protocols