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Rocaglamide (Rocaglamide A)

Catalog No.: GC33426

Rocaglamide (Rocaglamide A) is isolated from the genus Aglaia (family Meliaceae). 

Rocaglamide (Rocaglamide A) Chemical Structure

Size Price Stock Qty
500μg
$180.00
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1mg
$225.00
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5mg
$495.00
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10mg
$855.00
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25mg
$1,665.00
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50mg
$2,835.00
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100mg
$4,455.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

HepG2 and Huh-7 cells

Preparation Method

HepG2 and Huh-7 cells were seeded in 96-well plates in complete culture medium and incubated for 24 h. The cells were then exposed to 100 nM Rocaglamide (Rocaglamide A) and TRAIL for 24 h.

Reaction Conditions

100 nM;24h

Applications

Rocaglamide (Rocaglamide A) significantly enhanced TRAIL induced apoptosis.

Animal experiment [2]:

Animal models

Female SCID mice (6-week-old)

Preparation Method

The Huh-7 cells, suspended in 100 µl mix, were implanted subcutaneously into the right flank of 10 female SCID mice (6-week-old) and then randomly divided into two equal groups, one of which received an intraperitoneal injection of Rocaglamide (Rocaglamide A) (2.5 mg/kg in 80 µl olive oil; n=5) and the other, used as a vehicle contro. These treatments were performed once daily for 32 days and the tumor volumes and body weights of the animals were measured twice a week.

Dosage form

2.5 mg/kg; i.p.; 32 days

Applications

Rocaglamide (Rocaglamide A) induced tumor cell apoptosis in a SCID mouse model (Huah-7 cells) without causing weight loss in mice, and no significant signs of toxicity were observed during treatment, suggesting that Rocaglamide is generally well tolerated in vivo.

References:

[1]. Luan Z, He Y, et,al. Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation. Mol Med Rep. 2015 Jan;11(1):203-11. doi: 10.3892/mmr.2014.2718. Epub 2014 Oct 21. PMID: 25333816; PMCID: PMC4237083.

Background

Rocaglamide (Rocaglamide A) is isolated from the genus Aglaia (family Meliaceae). Rocaglamide (Rocaglamide A)(IC50 of 50 nM) inhibits the function of the translation initiation factor eIF4A, a DEAD box RNA helicase [1,2].

Rocaglamide (Rocaglamide A) (100 nM;24h) significantly enhanced TRAIL induced apoptosis[4]. Rocaglamide (Rocaglamide A) (20- 100 nM;48h)can induce 10-30% apoptosis of L1236 and KM-H2 cells [3]. Rocaglamide (Rocaglamide A) are able to suppress the PMA-induced expression of NF-kappaB target genes and sensitize leukemic T cells to apoptosis induced by TNFalpha, cisplatin, and gamma-irradiation [5]. Rocaglamide (Rocaglamide A)( 30/50 nM;21d) prevented TNF-α mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells [6].

Rocaglamide (Rocaglamide A)( 2.5 mg/kg; i.p.; 32 days) induced tumor cell apoptosis in a SCID mouse model (Huah-7 cells) without causing weight loss in mice, and no significant signs of toxicity were observed during treatment, suggesting that Rocaglamide is generally well tolerated in vivo[4]. Rocaglamide (Rocaglamide A)( 0.5 mg/kg; i.p.; five times per week for two weeks) overcomes CPT resistance in U266 in vitro and significant increases in anti-tumor efficacies of CPT in mice xenografted with U266[7].

References:
[1]. Santagata S, Mendillo ML, et,al. Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science. 2013 Jul 19;341(6143):1238303. doi: 10.1126/science.1238303. PMID: 23869022; PMCID: PMC3959726.
[2]. Kim S, Salim AA, Swanson SM and Kinghorn AD: Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy. Anticancer Agents Med Chem. 6:319-345. 2006.
[3]. Giaisi M, KÖhler R, et,al. Rocaglamide and a XIAP inhibitor cooperatively sensitize TRAIL-mediated apoptosis in Hodgkin's lymphomas. Int J Cancer. 2012 Aug 15;131(4):1003-8. doi: 10.1002/ijc.26458. Epub 2011 Nov 8. PMID: 21952919.
[4]. Luan Z, He Y, et,al. Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation. Mol Med Rep. 2015 Jan;11(1):203-11. doi: 10.3892/mmr.2014.2718. Epub 2014 Oct 21. PMID: 25333816; PMCID: PMC4237083.
[5]. Baumann B, Bohnenstengel F, et,al. Rocaglamide derivatives are potent inhibitors of NF-kappa B activation in T-cells. J Biol Chem. 2002 Nov 22;277(47):44791-800. doi: 10.1074/jbc.M208003200. Epub 2002 Sep 16. PMID: 12237314.
[6]. Li A, Yang L, et,al. Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling. Mol Cells. 2015 Nov;38(11):941-9. doi: 10.14348/molcells.2015.2353. Epub 2015 Nov 6. PMID: 26549505; PMCID: PMC4673408.
[7]. Wu Y, Giaisi M, et,al. Rocaglamide breaks TRAIL-resistance in human multiple myeloma and acute T-cell leukemia in vivo in a mouse xenogtraft model. Cancer Lett. 2017 Mar 28;389:70-77. doi: 10.1016/j.canlet.2016.12.010. Epub 2016 Dec 18. PMID: 27998762.

Chemical Properties

Cas No. 84573-16-0 SDF
Synonyms Rocaglamide A; Roc-A
Chemical Name N/A
Canonical SMILES O1C2=CC(OC)=CC(OC)=C2[C@]2(O)[C@H](O)[C@H](C(N(C)C)=O)[C@@H](C3=CC=CC=C3)[C@]12C1=CC=C(OC)C=C1 |&1:11,13,15,21,28,r|
Formula C29H31NO7 M.Wt 505.56
Solubility 150 mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Research Update

Rocaglamide promotes the infiltration and antitumor immunity of NK cells by activating cGAS-STING signaling in non-small cell lung cancer

Int J Biol Sci.2022 Jan 1;18(2):585-598. PMID: 35002511 DOI: 10.7150/ijbs.65019

Background: Natural killer (NK) cell-based immunotherapy is clinically limited due to insufficient tumor infiltration in solid tumors. We have previously found that the natural product rocaglamide (RocA) can enhance NK cell-mediated killing of non-small cell lung cancer (NSCLC) cells by inhibiting autophagy, and autophagic inhibition has been shown to increase NK cell tumor infiltration in melanoma. Therefore, we hypothesized that RocA could increase NK cell infiltration in NSCLC by autophagy inhibition. Methods: Flow cytometry, RNA-sequencing, real-time PCR, Western blotting analysis, and xenograft tumor model were utilized to assess the infiltration of NK cells and the underlying mechanism. Results: RocA significantly increased the infiltration of NK cells and the expressions of CCL5 and CXCL10 in NSCLC cells, which could not be reversed by the inhibitions of autophagy/ULK1, JNK and NF-κB. However, such up-regulation could be suppressed by the inhibitions of TKB1 and STING. Furthermore, RocA dramatically activated the cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) signaling pathway, and the inhibition/depletion of STING ablated the up-regulation of CCL5 and CXCL10, NK cell infiltration, and tumor regression induced by RocA. Besides, RocA damaged mitochondrial DNA (mtDNA) and promoted the cytoplasmic release of mtDNA. The mPTP inhibitor cyclosporin A could reverse RocA-induced cytoplasmic release of mtDNA. Conclusions: RocA could promote NK cell infiltration by activating cGAS-STING signaling via targeting mtDNA, but not by inhibiting autophagy. Taken together, our current findings suggested that RocA was a potent cGAS-STING agonist and had a promising potential in cancer immunotherapy, especially in NK cell-based immunotherapy.

Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species

Nat Prod Rep2014 Jul;31(7):924-39.PMID: 24788392DOI: 10.1039/c4np00006d

Covering: 2006 to 2013. Investigations on the chemistry and biology of rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species during the period 2006-2013 are reviewed. Included are new phytochemical studies of naturally occurring rocaglamide derivatives, an update on synthetic methods for cyclopenta[b]benzofurans, and a description of the recent biological evaluation and mechanism-of-action studies on compounds of this type.

Rocaglamide and silvestrol: a long story from anti-tumor to anti-coronavirus compounds

Nat Prod Rep.2021 Jan 1;38(1):18-23. PMID: 32699874DOI: 10.1039/d0np00024h

Covering: up to the beginning of 2020Many natural substances have been transformed again and again with regard to their pharmaceutical-medical potential, including new members of a growing class of natural products, the flavaglines. Important representatives are rocaglamide and silvestrol, isolated from the Aglaia species, which are highlighted here. These products started as potential anti-tumor agents five decades ago and have recently proved to be very promising antiviral agents, especially against RNA viruses. Today they are discussed as potential starting compounds for developing drug candidates and therapeutics.

Progress in the total synthesis of rocaglamide

ISRN Org Chem.2011 Apr 4;2011:239817. PMID: 24052818DOI: 10.5402/2011/239817

considerable insecticidal activities and excellent potential as a therapeutic agent candidate in cancer chemotherapy; the genus Aglaia has been subjected to further investigation. Both the structural complexity of rocaglamide and its significant activity make it an attractive synthetic target. Stereoselective synthesis of the dense substitution pattern of these targets is a formidable synthetic challenge: the molecules bear five contiguous stereocenters and cis aryl groups on adjacent carbons. In past years of effort, only a handful of completed total syntheses have been reported, evidence of the difficulties associated with the synthesis of rocaglate natural products. The advance on total synthesis of rocaglamide was mainly reviewed from intramolecular cyclization and biomimetic cycloaddition approach.

Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling

Mol Cells.2015 Nov;38(11):941-9. PMID: 26549505DOI: 10.14348/molcells.2015.2353

Rheumatoid arthritis is a chronic inflammatory disease that leads to bone and cartilage erosion. The inhibition of osteoblast differentiation by the inflammatory factor TNF-α is critical for the pathogenesis of rheumatoid arthritis. To modulate TNF-α mediated inhibition of osteoblast differentiation is required to improve therapeutic efficacy of rheumatoid arthritis. Here, we explored the potential role of rocaglamide-A, a component of Aglaia plant, in osteoblast differentiation. Rocaglamide-A prevented TNF-α mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells. Mechanistically, Rocaglamide-A inhibited the phosphorylation of NF-κB component p65 protein and the accumulation of p65 in nucleus, which resulted in the diminished NF-κB responsible transcriptional activity. Oppositely, overexpression of p65 reversed rocaglamide-A's protective effects on osteoblast differentiation. Collectively, rocaglamide-A protected and stimulated osteoblast differentiation via blocking NF-κB pathway. It suggests that rocaglamide-A may be a good candidate to develop as therapeutic drug for rheumatoid arthritis associated bone loss diseases.

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