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177262-30-5

中文名稱 DIDESMETHYLROCAGLAMIDE
英文名稱 1H-Cyclopenta[b]benzofuran-2-carboxamide, 2,3,3a,8b-tetrahydro-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-3-phenyl-, (1R,2R,3S,3aR,8bS)-
CAS 177262-30-5
分子式 C27H27NO7
分子量 477.51
MOL 文件 177262-30-5.mol
177262-30-5 結(jié)構(gòu)式 177262-30-5 結(jié)構(gòu)式

基本信息

英文別名
Didesmethylrocaglamide
(1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-2-carboxamide
1H-Cyclopenta[b]benzofuran-2-carboxamide, 2,3,3a,8b-tetrahydro-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-3-phenyl-, (1R,2R,3S,3aR,8bS)-

物理化學(xué)性質(zhì)

沸點(diǎn)691.4±55.0 °C(Predicted)
密度1.379±0.06 g/cm3(Predicted)
儲(chǔ)存條件-20°C儲(chǔ)存
溶解度DMSO: 100 mg/mL (209.42 mM)
酸度系數(shù)(pKa)11.70±0.70(Predicted)
形態(tài)Solid
顏色White to off-white

常見(jiàn)問(wèn)題列表

生物活性
Didesmethylrocaglamide 是一種 Rocaglamide 的衍生物,也是一種有效的真核起始因子 4A (eIF4A) 抑制劑。Didesmethylrocaglamide 具有有效的生長(zhǎng)抑制活性,IC50 為 5 nM。Didesmethylrocaglamide 抑制多種促進(jìn)生長(zhǎng)的信號(hào)通路,并誘導(dǎo)腫瘤細(xì)胞凋亡 (apoptosis)。抗腫瘤活性。
靶點(diǎn)

Eukaryotic initiation factor 4A (eIF4A)

體外研究

Didesmethylrocaglamide (5 nM, and 10 nM; 72 hours; MPNST cells) treatment arrests MPNST cells at G2-M, increases the sub-G1 population, induces cleavage of caspases and PARP, and elevates the levels of the DNA-damage response marker γH2A.X, while decreasing the expression of AKT and ERK1/2.
Didesmethylrocaglamide inhibits MPNST cell proliferation by inducing cell cycle arrest at G2/M and subsequently, cell death. Didesmethylrocaglamide-treated 697-R cells exhibits IC 50 values is very similar to those of parental 697 cells (4 vs 3nM of IC 50 , respectively).
Didesmethylrocaglamide induces apoptosis in both neurofibromatosis type 1 (NF1)-expressing and NF1-deficient MPNST cells, possibly subsequent to the activation of the DNA damage response. Didesmethylrocaglamide-treated sarcoma cells show decreased levels of multiple oncogenic kinases, including insulin-like growth factor-1 receptor.

Western Blot Analysis

Cell Line: Malignant peripheral nerve sheath tumors (MPNST) cells
Concentration: 5 nM, and 10 nM
Incubation Time: 72 hours
Result: Induced cleavage of caspases and PARP, and elevated the levels of the DNA-damage response marker γH2A.X.
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