A-443654

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性 Akt 抑制剂，Akt1 的 Ki 值为 0.16 nM。

A potent and selective Akt inhibitor with Ki of 0.16 nM for Akt1; has equal potency against Akt1, Akt2, or Akt3 within cells, displays 40-fold selectivity over PKA, and CMGC family kinases; inhibits Akt-dependent signal transduction, inhibits proliferation of MiaPaCa-2 cells with EC50 of 0.1 uM; inhibits tumor growth in vivo, and is more potent and more selective than A-674563.

A-443654 exhibits a?Ki?of 160 pM, a 30,000-fold improvement in potency versus the initial lead molecule. A-443654 is 40-fold selective for Akt over PKA. A-443654 inhibits Akt1, Akt2, or Akt3 equally within cells. A-443654 reduces the P-GSK3 in a dose-responsive manner in all three cell lines. A-443654 inhibits the proliferation of tumor cells with EC50 of 0.1 μM. A-443654-induced morphological changes occur very rapidly (within 2 to 4 h) in both 10A and 10CA1a cells, with 10CA1a cells more sensitive to A-443654 than the 10A cells. A-443654 alone at 2 μM causes the 10CA1a cells, but not the 10A cells, to detach from the plate after 12 h, whereas 1 μM of A-443654 causes 10CA1a cells to detach from the plate after 12 h. FACScan Analysis of rapamycin and A-443654 effects on DNA content in 10A and 10CA1a cells. In contrast, A-443654 at 2 and 5 μM decreases Bcl-2 levels by 30 to 40% in the 10CA1a cells at 8h. The combination of rapamycin with 2 or 5 μM A-443654, however, markedly decreases Bcl-2 protein levels by appr 40 to 50% in the 10A cells and by appr 70% in the 10CA1a cells, respectively. A-443654 demonstrates the greatest selective effect on the mutant cells compared to the WT cells with greater than 3.5 fold relative growth inhibition of the mutant cells.

A-443654 (7.5 mg/kg/d, s.c.) inhibits tumor growth in the 3T3-Akt1 flank tumor model. A-443654 (50 mg/kg, s.c.) induces apoptosis in 3T3-Akt1 flank tumors. A-443654 (30 mg/kg, s.c.) leads to increased levels of phosphorylated Akt1 in MiaPaCa-2 tumors.

A 443654 | A443654

Cytoskeleton/Cell Adhesion Molecules

Akt

Akt

Cancer

——

552325-16-3

397.4723

C24H23N5O

>98% (HPLC)

10 mM in DMSO

N[C@H](COC1=CC(C2=CC3=C(C)NN=C3C=C2)=CN=C1)CC4=CNC5=C4C=CC=C5

1H-Indole-3-ethanamine, .alpha.-[[[5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy]methyl]-, (.alpha.S)-

(-20℃)

With Ice Pack

≥ 2 years