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A-674563

CAS No. : 552325-73-2

產品活性：A-674563 is an orally active and selective Akt1 inhibitor with a K_i of 11 nM.

研究領域：PI3K/Akt/mTOR

作用靶點：Akt

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 µM (SW684) to 0.35 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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