A-443654

SKU: orb1308705

Description

A-443654 is a potent pan-Akt inhibitor with equipotent activity against Akt1, Akt2, and Akt3 isoforms, exhibiting a cellular Ki of 160 pM. This compound is widely used in biochemical and cellular research to investigate the PI3K/Akt signaling pathway in cancer and metabolic studies, with applications in both in vitro and in vivo experimental models.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Metabolism Research, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 552325-16-3
• MW: 397.47
• Purity: 99.51% (May vary between batches)
• Formula: C₂₄H₂₃N₅O
• SMILES: C([C@@H](COC=1C=C(C=NC1)C=2C=C3C(=CC2)NN=C3C)N)C=4C=5C(NC4)=CC=CC5
• Target: PKA,Casein Kinase,Akt,GSK-3,PKC,ERK,VEGFR,S6 Kinase,FLT,MAPK,Chk,CDK,Src
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (10.06 mM);DMSO:100 mg/mL (251.59 mM)

Bioactivity

• Target IC50:
  RSK2:11 nM (Ki)|PKA:6.3 nM (Ki)|Akt2:160 pM (Ki)|PKCγ:24 nM (Ki)|CDK2:24 nM (Ki)|GSK-3β:41 nM (Ki)|CK2:2.4 μM (Ki)|Akt1:160 pM (Ki)|Src:2.6 μM (Ki)|Akt3:160 pM (Ki)|KDR:3.1 μM (Ki)|MAPK-AP2:3.3 μM (Ki)|Flt1:3.6 μM (Ki)|c-Kit:1.2 μM (Ki)|PKCδ:33 nM (Ki)|ERK2:340 nM (Ki)|Chk1:2.3 μM (Ki)
• In Vivo:
  A-443654, administered subcutaneously at a dosage of 7.5 mg/kg per day, effectively inhibits tumor growth in the 3T3-Akt1 flank tumor model. At a higher concentration of 30 mg/kg, this compound increases phosphorylated Akt1 levels in MiaPaCa-2 tumors. Furthermore, a dosage of 50 mg/kg induces apoptosis in 3T3-Akt1 flank tumors .
• In Vitro:
  A-443654 demonstrates a significant improvement in potency with a K_i of 160 pM, a 30,000-fold increase compared to the initial lead molecule. It effectively reduces P-GSK3 in a dose-dependent manner across three cell lines and exhibits 40-fold greater selectivity for Akt over PKA, equally inhibiting Akt1, Akt2, and Akt3 within cells. Morphological changes induced by A-443654 are rapid, occurring within 2 to 4 hours in 10A and 10CA1a cells, with the latter being more sensitive. The compound hinders tumor cell proliferation, with an EC50 of 0.1 μM, and shows marked selectivity for mutant cells, inhibiting their growth more than 3.5 times compared to wild-type (WT) cells. Furthermore, A-443654, especially when combined with rapamycin, significantly decreases Bcl-2 protein levels in 10A and 10CA1a cells, exhibiting a notable reduction in 10CA1a cells by approximately 70%. At 2 μM, A-443654 alone prompts 10CA1a cells to detach from the plate after 12 hours, illustrating a differential response compared to 10A cells, which remain unaffected at the same concentration.

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

PKB, PKA, PKCγ, PKCδ, SRC, S6 Kinase, S6Kinase, Protein kinase B, RSK2, inhibit, KDR, ERK2, GSK3, GSK-3β, GSK3β, Flt1, Inhibitor, MAPK, MAPK-AP2, CDK2, Casein Kinase, CaseinKinase, Chk1, CK2, cKIT, Akt, A 443654, A443654, A-443654, Akt1, Akt3, Akt2

Compound Identifiers

PubChem CID

10172943