A-674563

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

A-674563 是一种有效的、选择性的、口服的 AKT 抑制剂，Ki 为 11 nM (Akt1)。

A-674563 is a potent, selective and orally available AKT inhibitor with Ki of 11 nM (Akt1); increases the efficacy of paclitaxel in a PC-3 xenograft model; enhances the transcription of several chondrocyte marker genes, including Col2a1, Acan and Col11a2, in mouse primary chondrocytes by inhibiting Sox9 degradation through the ubiquitin-proteasome pathway; also suppresses FLT3-ITD positive AML both in vitro and in vivo.(In Vitro):A-674563 slows proliferation of tumor cells with an EC50 of 0.4 μM. A563 (0-10 μM) significantly 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±0.034 μM (SW684) to 0.35 ±0.06 μM (SKLMS1). 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, activates caspase-3/9 and apoptosis in U937 and AmL progenitor cells, and manipulates other signalings in AmL cells whiling blocking Akt. (In Vivo):A-674563 (40 mg/kg/d, p.o.) shows no significant monotherapy activity, but the efficacy of the combination therapy (A-674563+paclitaxel) is significantly improved in the PC-3 prostate cancer xenograft model. A-674563 (20, 100 mg/kg) increases plasma insulin in an oral glucose tolerance test. 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) potently inhibits A375 xenograft growth in mice. A-674563 (15, 40 mg/kg) injection inhibits U937 xenograft in vivo growth, and improves mice survival.

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A 674563 | A674563

Cytoskeleton/Cell Adhesion Molecules

Akt

Akt1|CDK2|ERK2|GSK-3β|PKA

Cancer

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552325-73-2

358.4

C22H22N4O

>98% (HPLC)

10 mM in DMSO

N[C@@H](CC1=CC=CC=C1)COC2=CC(C3=CC4=C(NN=C4C)C=C3)=CN=C2

Benzeneethanamine, a-[[[5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy]methyl]-, (aS)-

(-20℃)

With Ice Pack

≥ 2 years