Silvestrol

Silvestrol 是一种真核翻译起始因子 4A (eIF4A) 抑制剂，从 Agave americana Linn 中分离出来。Silvestrol 诱导自噬和半胱天冬酶介导的细胞凋亡。

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库存: 现货

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1mg

￥10687.00

8550.00

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2mg

￥17625.00

14100.00

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货号: ajci7152
CAS: 697235-38-4
别名: (1R,2R,3S,3AR,8BS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-二羟基乙基]-3-甲氧基-1,4-二氧己环-2-基]氧基]-2,3,3A,8B-四氢-1,8B-二羟基-8-甲氧基-3A-(4-甲氧基苯基)-3-苯基-1H-环戊烯并[B]苯并呋喃-2-羧酸甲酯,(-)-Silvestrol
分子式: C34H38O13
分子量: 654.66
纯度: >98%
溶解度: Soluble in DMSO
储存: Store at -20°C
库存: 现货

Background

Silvestrol inhibited protein synthesis in MDA-MB-231 breast and PC-3 prostate cancer cell lines with IC50 ~60 nM following a 1 h exposure) [1]. Silvestrol inhibited cell growth with an IC50 of 12.5-86 nM in four different HCC cell lines [3].
Silvestrol, a member of flavagline family of natural products from the genus of Aglaia exhibiting anti-cancer activity in vitro and in vivo and inhibiting translation initiation, was shown to be capable of modulating chemosensitivity in a mechanism-based mouse model.
Preclinical study: A previous study demonstrated that silvestrol showed antileukemia activity at nanomolar concentrations in both FLT3-wt overexpressing (THP-1) and FLT3-ITD (MV4-11) expressing AML cell lines (IC50 = 3.8 and 2.7 nM, respectively) and patients' primary blasts [IC50 = ~12 nM (FLT3-wt) and ~5 nM (FLT3-ITD)]. Moreover, silvestrol was observed to efficiently inhibite FLT3 translation resulting in a decrese of FLT3 protein expression by 80–90%. Animal study indicated that the median survival of silvestrol-treated mice significantly increased (silvestrol-treated vs vehicle-treated = 63 vs 29 days postengraftment) [2]. Another study showed that silvestrol could increase the activities of apoptosis and caspase 3/7. In vivo, the antitumor effect was found with 0.4 mg/kg silvestrol, and the survival of tumor-bearing mice was improved with a median survival time of 42 and 28 days in the silvestrol and control groups, respectively [3].
Clinical study: Currently, there is no clinical data about the anti-cancer efficacy of silvestrol. A grant application proposeed to pursue a Phase I clinical trial to assess the safety, maximum tolerated dose, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of silvestrol in patients with relapsed, refractory Chronic lymphocytic leukemia (Pre-Clinical and Clinical Development of Silvestrol in Chronic Lymphocytic).
参考文献:
[1] Cencic R, Carrier M, Galicia-Vázquez G, Bordeleau ME, Sukarieh R, Bourdeau A, Brem B, Teodoro JG, Greger H, Tremblay ML, Porco JA Jr, Pelletier J Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol. PLoS One. 2009;4(4):e5223. doi: 10.1371/journal.pone.0005223.
[2] Alachkar H, Santhanam R, Harb JG, Lucas DM, Oaks JJ, Hickey CJ, Pan L, Kinghorn AD, Caligiuri MA, Perrotti D, Byrd JC, Garzon R, Grever MR, Marcucci G. Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia. J Hematol Oncol. 2013;6:21. doi: 10.1186/1756-8722-6-21.
[3] Kogure T, Kinghorn AD, Yan I, Bolon B, Lucas DM, Grever MR, Patel T. Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer. PLoS One. 2013;8(9):e76136. doi: 10.1371/journal.pone.0076136.

Protocol

Cell experiment [1]:
Cell lines	Human HCC cells
Preparation method	This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	0 ~ 200 nM; 72 hrs
Applications	Silvestrol potently inhibited human HCC cell growth in a concentration-dependent manner, with an IC50 value of 23.9 nM in PLC/PRF-5 cells, 12.5 nM in Hep-3B cells, 14.6 nM in Huh-7 cells and 86 nM in HepG2 cells.
Animal experiment [1]:
Animal models	Nude mice bearing human HCC xenografts
Dosage form	0.4 or 1 mg/kg; i.p.; 5 days/week, for 4 weeks
Applications	In nude mice bearing human HCC xenografts, a therapeutic response was observed in 36.4% of mice receiving 1 mg/kg Silvestrol and in 20% of mice receiving 0.4 mg/kg Silvestrol. At both doses, Silvestrol significantly increased the survival.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
参考文献: [1]. Kogure T, Kinghorn AD, Yan I, Bolon B, Lucas DM, Grever MR, Patel T. Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer. PLoS One. 2013;8(9):e76136. doi: 10.1371/journal.pone.0076136.