发布时间 : 星期一 文章A-674563 - Akt 抑制剂- MedChemExpress - 图文更新完毕开始阅读c5041008dc3383c4bb4cf7ec4afe04a1b171b05c
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Inhibitors?Agonists?Screening Librarieswww.MedChemExpress.cnA-674563Cat. No.:CAS No.:HY-13254552325-73-2C??H??N?O358.44AktPI3K/Akt/mTOR4°C, stored under nitrogen*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)分?式:分?量:作?靶点:作?通路:储存?式:溶解性数据体外实验DMSO : 83.33 mg/mL (232.48 mM; Need ultrasonic)H2O : < 0.1 mg/mL (insoluble)Mass1 mg2.7899 mL0.5580 mL0.2790 mL5 mg13.9493 mL2.7899 mL1.3949 mL10 mg27.8987 mL5.5797 mL2.7899 mLSolventConcentration制备储备液1 mM5 mM10 mM请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存?式和期限。体内实验请根据您的实验动物和给药?式选择适当的溶解?案，配制前请先配制澄清的储备液，再依次添加助溶剂 (为保证实验结果的可靠性，体内实验的?作液，建议您现?现配，当天使?；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分?是指该溶剂在您配制终溶液中的体积占?)：1.请依序添加每种溶剂： 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: ≥ 2.08 mg/mL (5.80 mM); Clear solution BIOLOGICAL ACTIVITY?物活性A-674563是有效，选择性的 Akt1 抑制剂，Ki为11 nM。1/3Master of Small Molecules —您?边的抑制剂?师
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IC50 & TargetAkt111 nM (Ki)SRC13 μM (Ki)CK25.4 μM (Ki)PKA16 nM (Ki)CDK246 nM (Ki)Chk12.6 μM (Ki)PKCγ1.2 μM (Ki)ERK2260 nM (Ki)RSK2580 nM (Ki)PKCδ360 nM (Ki)GSK3β110 nM (Ki)MAPK-AP21.1 μM (Ki)体外研究A-674563 slows proliferation of tumor cells with an EC50 of 0.4 μM [1]. 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 [2]. 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 [3]. 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 [4].体内研究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 [1]. 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 [2]. A-674563 (25, 100 mg/kg, lavage daily) potently inhibits A375 xenograft growth in mice [3]. A-674563 (15, 40 mg/kg) injection inhibits U937 xenograft in vivo growth, and improves mice survival [4]. PROTOCOLCell Assay [1]The cells on 96-well plates are gently washed with 200 μL of PBS. Alamar Blue reagent is diluted 1:10 in normal growth media. The diluted Alamar Blue reagent (100 μL) is added to each well on the 96-well plates and incubated until the reaction is complete. Analysis is done using an fmax Fluorescence Microplate Reader, set at the excitation wavelength of 544 nm and emission wavelength of 595 nm. Data are analyzed using SOFTmax PRO software.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration [1]Immunocompromised male scid mice are at 6 to 8 weeks of age. The 1×106 3T3-Akt1 or 2×106 MiaPaCa-2 and PC-3 cells in 50% Matrigel are inoculated s.c. into the flank. For early treatment studies, mice are randomLy assigned to treatment groups and therapy is initiated the day after inoculation. Ten animals are assigned to each group, including controls. For established tumor studies, tumors are allowed to reach a designated size and mice are assigned to treatment groups of equal tumor size (n=10 mice per group). 2/3Master of Small Molecules —您?边的抑制剂?师
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Tumor size is evaluated by twice weekly measurements with digital calipers. Tumor volume is estimated using the formula: V=L×W2/2. A-443654 is given s.c. in a vehicle of 0.2% HPMC. A-674563 is given orally in a vehicle of 5% dextrose. Gemcitabine and paclitaxel are added to the assay.MCE has not independently confirmed the accuracy of these methods. They are for reference only. 客户使?本产品发表的科研?献? J Proteome Res. 2018 Oct 5;17(10):3360-3369.? Oncotarget. 2016 May 17;7(20):29131-42.See more customer validations on www.MedChemExpress.cn REFERENCES[1]. Luo Y, et al. Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol Cancer Ther, 2005, 4(6), 977-986.[2]. Zhu QS, et al. Soft tissue sarcoma cells are highly sensitive to AKT blockade: a role for p53-independent up-regulation of GADD45 alpha. Cancer Res, 2008, 68(8), 2895-2903.[3]. Zou Y, et al. Pre-clinical assessment of A-674563 as an anti-melanoma agent. Biochem Biophys Res Commun. 2016 Aug 12;477(1):1-8.[4]. Xu L, et al. Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells. Biochem Biophys Res Commun. 2016 Apr 15;472(4):662-8.[5]. Wang A, et al. Dual inhibition of AKT/FLT3-ITD by A674563 overcomes FLT3 ligand-induced drug resistance in FLT3-ITD positive AML. Oncotarget. 2016 May 17;7(20):29131-42.McePdfHeightCaution: Product has not been fully validated for medical applications.
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