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
中文名称 | 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 |
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中文同义词 | 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;MTOR抑制剂(WYE-354);4-(6-(4-((甲氧羰基)氨基)苯基)-4-吗啉基-1H-吡唑并[3,4-D]嘧啶-1-基)哌啶-1-甲酸甲酯;化合物AOB2796 |
英文名称 | WYE-354 |
英文同义词 | WYE-354;4-[6-[4-[(Methoxycarbonyl)amino]phenyl]-4-(4-morpholinyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylic acid methyl ester;methyl 4-[6-[4-(methoxycarbonylamino)phenyl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate;WYE-354 (Degrasyn);WYE-354;WYE 354; WYE354;Methyl 4-(6-(4-(methoxycarbonylamino)phenyl)-4-morpholino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pip;CS-441;1-Piperidinecarboxylic acid, 4-[6-[4-[(methoxycarbonyl)amino]phenyl]-4-(4-morpholinyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-, methyl ester |
CAS号 | 1062169-56-5 |
分子式 | C24H29N7O5 |
分子量 | 495.53 |
EINECS号 | |
相关类别 | 小分子抑制剂,天然产物;细胞生物学试剂;Amines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators;PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K |
Mol文件 | 1062169-56-5.mol |
结构式 | ![]() |
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 性质
密度 | 1.46 |
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储存条件 | Sealed in dry,Store in freezer, under -20°C |
溶解度 | DMSO 中≥49.6 mg/mL;不溶于水;不溶于乙醇 |
形态 | 固体 |
酸度系数(pKa) | 13.42±0.70(Predicted) |
颜色 | 白色至米白色 |
mTOR 5 nM (IC 50 ) |
mTORC1
|
mTORC2
|
PI3K alpha 1.89 μM (IC 50 ) |
PI3K gamma 7.37 μM (IC 50 ) |
Autophagy
|
In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-354 inhibits recombinant mTOR enzyme with an IC 50 of 5 nM. Cell viability is analyzed by MTS assay. G-415 and TGBC-2TKB cell lines are treated with increasing concentrations of WYE-354 (0.1, 1, 5 and 10 μM) for 24, 48, and 72 hours. WYE-354 significantly reduces cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines (P<0.001). A decrease in cell viability is not observed at a dose of 100 nM, except for the TGBC-2TKB cell line after 72 hours of treatment.
The effect of Rapamycin and WYE-354 on tumor growth is evaluated in xenograft GBC tumor models. 2×10 6 or 5×10 6 cells of G-415 or TGBC2TKB, respectively, are xenotransplanted into NOD-SCID mice subcutaneously. When tumors reach an average volume of 100 mm 3 , the mice are treated either with Rapamycin or WYE354. Rapamycin is administered i.p. at a concentration of 10 mg/kg, daily for 5 days per week for 3 weeks, while WYE-354 is administrated at a daily i.p. dose of 50 mg/kg for 5 days. Mice are sacrificed 30 days after the initiation of the treatments and an autopsy is performed that include removal of the entire tumor area. Mice treated with WYE-354 exhibit 68.6% and 52.4% reduction in average tumor size (P<0.01; P<0.01), as well as 82.9% and 45.5% (P<0.01; ns) reduction in tumor weight, respectively.
A pyrazolopyrimidines derivative that is a potent and ATP-competitive mTOR inhibitor with much reduced activity against PI 3-Kα or PI 3-Kγ. WYE-354 is equally potent against mTORC1 and mTORC2 activiti es in HEK293 immune complex kinase assays using S6K and Akt as the respective substrate (IC50 <200 nM; [ATP] = 100 μM) and effectively blocks cellular phosphorylation of S6K on T389 and Akt on S473 bo th in cultures and in a murine xenograft model, resulting in a significant suppression of PC3MM2-derived tumor growth (by 86% on day 7; 50 mg/kg, i.p twice per day) in vivo.
安全信息
更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
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2024/08/19 | HY-12034 | WYE-354 | 1 mg | 209元 | |
2024/08/19 | HY-12034 | 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 WYE-354 | 1062169-56-5 | 5mg | 650元 |