A-674563

SKU: orb1688647

Description

A-674563

Research Area

Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 552325-73-2
• MW: 358.44
• Purity: 99.21%
• Formula: C₂₂H₂₂N₄O
• SMILES: Cl.Cc1n[nH]c2ccc(cc12)-c1cncc(OC[C@@H](N)Cc2ccccc2)c1
• Target: PKA,GSK-3,Akt,ERK,CDK
• Solubility: H2O:66 mg/mL (184.13 mM);DMSO:67 mg/mL (186.92 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.58 mM);Ethanol:15 mg/mL (41.85 mM)

Bioactivity

• Target IC50:
  ERK2:260 nM (Ki)|Chk1:2.6 μM (Ki)|MAPK-AP2:1.1 μM (Ki)|CDK2:46 nM (Ki)|SRC:13 μM (Ki)|PKCδ:360 nM (Ki)|RSK2:580 nM (Ki)|PKA:16 nM (Ki)|PKCγ:1.2 μM (Ki)|Akt1:11 nM(Ki)|CK2:5.4 μM (Ki)|GSK-3β:110 nM (Ki)
• 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. 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.
• In Vitro:
  A-674563 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.
• 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 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. (Only for Reference)

Storage & Handling

• Storage: store at low temperature | Pure form: -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

CDK2, Akt1, Akt, A 674563, A674563, A-674563, Inhibitor, ERK2, GSK-3β, GSK3, inhibit, PKA, PKB, Protein kinase B

Compound Identifiers

PubChem CID

73357690