(-)-Silvestrol - CAS 697235-38-4
Catalog number: 697235-38-4
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C34H38O13
Molecular Weight:
654.66
COA:
Inquire
Targets:
Apoptosis Inducer
Description:
A member of flavagline family of natural products from the genus of Aglaia, induces apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7; 5'myc-UTR-LUC inhibtior with IC50 of 0.8 nM.
Purity:
≥95%
Appearance:
Solid Powder
Synonyms:
Methyl (1R,2R,3S,3aR,8bS)-6-({(2S,3R,6R)-6-[(1R)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl}oxy)-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d] furan-2-carboxylate;
Solubility:
Soluble in DMSO
Storage:
Store at -20 °C
MSDS:
Inquire
Application:
Induces early autophagy and apoptosis in human melanoma cells.
Quality Standard:
Enterprise Standard
Shelf Life:
As supplied, 2 years from the QC date provided on the Certificate of Analysis, when stored properly
Quantity:
Milligrams-Grams
InChIKey:
GVKXFVCXBFGBCD-QKDMMWSPSA-N
InChI:
1S/C34H38O13/c1-40-20-12-10-19(11-13-20)34-27(18-8-6-5-7-9-18)26(30(38)42-3)29(37)33(34,39)28-23(41-2)14-21(15-24(28)47-34)45-32-31(43-4)44-17-25(46-32)22(36)16-35/h5-15,22,25-27,29,31-32,35-37,39H,16-17H2,1-4H3/t22-,25-,26-,27-,29-,31-,32-,33+,34+/m1/s1
Canonical SMILES:
CO[C@H]1[C@@H](O[C@H](CO1)[C@@H](CO)O)OC2=CC3=C(C(=C2)OC)[C@@]4([C@@H]([C@@H]([C@H]([C@@]4(O3)C5=CC=C(C=C5)OC)C6=CC=CC=C6)C(=O)OC)O)O
1.Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.
Hwang BY;Su BN;Chai H;Mi Q;Kardono LB;Afriastini JJ;Riswan S;Santarsiero BD;Mesecar AD;Wild R;Fairchild CR;Vite GD;Rose WC;Farnsworth NR;Cordell GA;Pezzuto JM;Swanson SM;Kinghorn AD J Org Chem. 2004 May 14;69(10):3350-8.
Two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol (1) and episilvestrol (2), were isolated from the fruits and twigs of Aglaia silvestris by bioassay-guided fractionation monitored with a human oral epidermoid carcinoma (KB) cell line. Additionally, two new baccharane-type triterpenoids, 17,24-epoxy-25-hydroxybaccharan-3-one (3) and 17,24-epoxy-25-hydroxy-3-oxobaccharan-21-oic acid (4), as well as eleven known compounds, 1beta,6alpha-dihydroxy-4(15)-eudesmene (5), ferulic acid (6), grasshopper ketone (7), apigenin, cabraleone, chrysoeriol, 1beta,4beta-dihydroxy-6alpha,15alpha-epoxyeudesmane, 4-hydroxy-3-methoxyacetophenone, 4-hydroxyphenethyl alcohol, ocotillone, and beta-sitosterol 3-O-beta-D-glucopyranoside, were also isolated and characterized. The structures of compounds 1-4 were elucidated by spectroscopic studies and by chemical transformation. The absolute stereochemistry of silvestrol (1) was established by a X-ray diffraction study of its di-p-bromobenzoate derivative, and the structure of 3 was also confirmed by single-crystal X-ray diffraction. The isolates and chemical transformation products were evaluated for cytotoxicity against several human cancer cell lines, and silvestrol (1) and episilvestrol (2) exhibited potent in vitro cytotoxic activity.
2.Synergistic effect of inhibiting translation initiation in combination with cytotoxic agents in acute myelogenous leukemia cells.
Cencic R;Carrier M;Trnkus A;Porco JA Jr;Minden M;Pelletier J Leuk Res. 2010 Apr;34(4):535-41. doi: 10.1016/j.leukres.2009.07.043. Epub 2009 Sep 1.
We have previously shown that inhibition of translation initiation, using the small molecule inhibitor silvestrol, induces apoptosis in a pre-clinical murine lymphoma model when combined with daunorubicin. Silvestrol blocks ribosome recruitment by targeting the RNA helicase, eIF4A, which is required for this process. Here we investigate the sensitivity of acute myelogenous leukemia (AML) cell lines to protein synthesis inhibition in combination with the standard cytotoxic agents daunorubicin, etoposide, and cytarabine. Silvestrol shows synergy with standard-of-care agents in AML cell lines and synergizes with ABT-737, a small molecule inhibitor of Bcl-X(L) and Bcl-2. The in vitro synergy between silvestrol and the cytotoxic drugs used in AML therapy provides a basis for in vivo evaluation of these combinations.
3.Translation inhibitors induce cell death by multiple mechanisms and Mcl-1 reduction is only a minor contributor.
Lindqvist LM;Vikström I;Chambers JM;McArthur K;Ann Anderson M;Henley KJ;Happo L;Cluse L;Johnstone RW;Roberts AW;Kile BT;Croker BA;Burns CJ;Rizzacasa MA;Strasser A;Huang DC Cell Death Dis. 2012 Oct 11;3:e409. doi: 10.1038/cddis.2012.149.
There is significant interest in treating cancers by blocking protein synthesis, to which hematological malignancies seem particularly sensitive. The translation elongation inhibitor homoharringtonine (Omacetaxine mepesuccinate) is undergoing clinical trials for chronic myeloid leukemia, whereas the translation initiation inhibitor silvestrol has shown promise in mouse models of cancer. Precisely how these compounds induce cell death is unclear, but reduction in Mcl-1, a labile pro-survival Bcl-2 family member, has been proposed to constitute the critical event. Moreover, the contribution of translation inhibitors to neutropenia and lymphopenia has not been precisely defined. Herein, we demonstrate that primary B cells and neutrophils are highly sensitive to translation inhibitors, which trigger the Bax/Bak-mediated apoptotic pathway. However, contrary to expectations, reduction of Mcl-1 did not significantly enhance cytotoxicity of these compounds, suggesting that it does not have a principal role and cautions that strong correlations do not always signify causality. On the other hand, the killing of T lymphocytes was less dependent on Bax and Bak, indicating that translation inhibitors can also induce cell death via alternative mechanisms.
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