A-674563 HCl (552325-73-2(free base))

Research use only, not for human use.

A-674563 is an orally available, ATP-competitive, and reversible inhibitor of Akt (Ki: 11 nM for Akt1) .

A-674563 hydrochloride is a potent and selective Akt1 inhibitor with Ki of 11 nM.

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.

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.

——

Cell Cycle/DNA Damage

CDK

CDK | ERK | PKA | PKC | Akt

——

——

2070009-66-2

394.9

C22H23ClN4O

>98% (HPLC)

In Vitro:?H2O : 100 mg/mL (253.23 mM; Ultrasonic) DMSO : 50 mg/mL (126.61 mM; Ultrasonic )

CC=1C=2C(=CC=C(C2)C=3C=C(OC[C@H](CC4=CC=CC=C4)N)C=NC3)NN1.Cl

——

(-20℃)

With Ice Pack

≥ 2 years