WYE-354
作者：齐岳
发布时间：2023-09-11
09:04:58
点击数：
产品名称：WYE-354
产品描述：
| 产品描述 | WYE-354(IC50=5 nM) is an effective, selective and ATP-competitive mTOR inhibitor. It blocks mTORC2/P-AKT(S473) and mTORC1/P-S6K(T389), not P-AKT(T308). The selectivity for mTOR is higher than PI3Kα (>100-fold) and PI3Kγ (>500-fold). |
| 靶点活性 | PI3Kγ:7.37 μM, mTOR:5 nM, PI3Kα:1.89 μM |
| 体外活性 | In HEK293 cells, WYE-354 (0.2 μM–5 μM) effectively inhibits both mTORC1 and mTORC2. In U87 mg and MDA361 cells, WYE-354 (0.3 μM–10 μM) significantly blocks mTOR signaling and Akt activation. In tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, A498, and HCT116, WYE-354 effectively inhibits proliferation with IC50 values ranging from 0.28 μM to 2.3 μM. In endothelial HUVEC cells, WYE-354 also inhibits both mTORC1 and mTORC2 signaling with IC50 values ranging from 10 nM to 1 μM, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively. The apoptosis induced by WYE-354 is accompanied by G1 cell cycle arrest and caspases activation.WYE-354 (10 nM–1 μM) activates mitogen-activated protein kinase (MAPK) signaling, which may be due to its inhibition of mTORC1. |
| 体内活性 | WYE-354 (50 mg/kg) potently inhibits mTOR signaling and tumor growth In a mice xenograft model of PTEN-null PC3 mM2 tumor. |
| 激酶实验 | The assays were incubated at room temperature for 2 hours. In 96-well plates (25 μL) contains 6 nM Flag-TOR(3.5) (estimated 5-10% purity), 1 μM His6-S6K and 100 μM ATP.For inhibitor versus ATP matrix competition, mTOR kinase reactions are carried out with varying concentrations of ATP (0, 25, 50 100, 200, 400 and 800 μM) in combination with varying concentrations of inhibitor.The assays are performed and detected by DELFIA employing the Euphospho-p70S6K T389 antibody. |
| 细胞实验 | Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116, are plated in 96-well plates at 1000 to 3000 cells per well for 24 hours, treated with DMSO or varying concentrations of WYE-354(0–50 μM, dissolved in DMSO) for72 hours. |
| 动物实验 | Nude mice (BALB/c, nu/nu, female) bearing PC3 mM2 xenograft were intraperitoneally injected with WYE-354（50 mg/kg）dissolved in 5% ethanol, 5% polysorbate 80, 5% PEG-400. |
| 别名 | 4-[6-[4-[(甲氧羰基)氨基]苯基]-4-(4-吗啉基)-1H-吡唑并[3,4-D]嘧啶-1-基]-1-哌啶羧酸甲酯 |
| 分子量 | 495.53 |
| 分子式 | C24H29N7O5 |
| CAS No. | 1062169-56-5 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
DMSO: 92 mg/mL (185.7 mM)
Ethanol: <1 mg/mL
H2O: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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公司介绍：
西安齐岳生物科技有限公司是集化学科研和定制与一体的高科技化学公司。业务范围包括化学试剂和产品的研发、生产、销售等。涉及产品为通用试剂的分销、非通用试剂的定制与研发，涵盖生物科技、化学品、中间体和化工材料等领域。
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