Powder: -20°C for 3 years | In solvent: -80°C for 1 year
A-443654 is a pan-Akt inhibitor. A-443654 has equal potency against Akt1, Akt2, or Akt3 within cells (Ki=160 pM).
説明 | A-443654 is a pan-Akt inhibitor. A-443654 has equal potency against Akt1, Akt2, or Akt3 within cells (Ki=160 pM). |
ターゲット&IC50 | CK2:2.4 μM (ki), Chk1:2.3 μM (ki), c-Kit:1.2 μM (ki), ERK2:340 nM (ki), Akt3:160 pM (ki), PKCδ:33 nM (ki), PKCγ:24 nM (ki), MAPK-AP2:3.3 μM (ki), KDR:3.1 μM (ki), PKA:6.3 nM (ki), CDK2:24 nM (ki), RSK2:11 nM (ki), Akt2:160 pM (ki), Src:2.6 μM (ki), Akt1:160 pM (ki), GSK-3β:41 nM (ki) |
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[1], and shows marked selectivity for mutant cells, inhibiting their growth more than 3.5 times compared to wild-type (WT) cells[3]. 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[2]. |
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 [1]. |
分子量 | 397.47 |
分子式 | C24H23N5O |
CAS No. | 552325-16-3 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 100 mg/mL (251.59 mM)
You can also refer to dose conversion for different animals. 詳細
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A-443654 552325-16-3 Angiogenesis Cell Cycle/Checkpoint Chromatin/Epigenetic Cytoskeletal Signaling MAPK Metabolism PI3K/Akt/mTOR signaling Stem Cells Tyrosine Kinase/Adaptors Casein Kinase FLT GSK-3 VEGFR ERK Chk CDK PKA Akt Src PKC S6 Kinase A443654 inhibit A 443654 Inhibitor PKB Protein kinase B inhibitor