WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406598
CAS#: 84573-16-0
Description: Rocaglamide is the first cyclopenta[b]benzofuran derivative (flavagline), isolated from Aglaia elliptifolia in 1982 by King and colleagues based on its antileukemic activity. Like other flavaglines, rocaglamide displays potent insecticidal, antifungal, anti-inflammatory and anticancer activities.
Hodoodo Cat#: H406598
Name: Rocaglamide
CAS#: 84573-16-0
Chemical Formula: C29H31NO7
Exact Mass: 505.21
Molecular Weight: 505.560
Elemental Analysis: C, 68.90; H, 6.18; N, 2.77; O, 22.15
Synonym: Rocaglamide; Rocaglamide A; RocA; NSC 326408.
IUPAC/Chemical Name: (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-2-carboxamide
InChi Key: DAPAQENNNINUPW-IDAMAFBJSA-N
InChi Code: InChI=1S/C29H31NO7/c1-30(2)27(32)23-24(17-9-7-6-8-10-17)29(18-11-13-19(34-3)14-12-18)28(33,26(23)31)25-21(36-5)15-20(35-4)16-22(25)37-29/h6-16,23-24,26,31,33H,1-5H3/t23-,24-,26-,28+,29+/m1/s1
SMILES Code: O=C([C@H]([C@H]1C2=CC=CC=C2)[C@@H](O)[C@]3(O)[C@@]1(C4=CC=C(OC)C=C4)OC5=CC(OC)=CC(OC)=C35)N(C)C
Appearance: White to off- white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Rocaglamide (RocA) is a heat shock factor 1 (HSF1) activation inhibitor with an IC50 of ~50 nM. |
| In vitro activity: | Whether RocA could reverse autophagic impairment of NSCLC (non small cell lung cancer) cell susceptibility to NK (natural killer) cell-mediated killing was determined. Rapamycin clearly impaired H460 and H1975 cell susceptibility to NK cell-mediated killing, whereas RocA significantly reversed this impairment (Figure 5(A,B)). A similar phenomenon was also observed in A549 cells stably expressing firefly luciferase (FLuc+ A549) cells upon rapamycin treatment (Figure 5(C)) or deferoxamine (DFO)-induced chemical hypoxia (Figure 5(D)) using a biophotonic cytotoxicity assay. Moreover, RocA did not increase expression of activating and death receptors or decrease the expression of inhibitory receptors on H460 and H1975 cell surfaces (Figure 5(E,F)). These results demonstrated that RocA could reverse autophagic impairment of NSCLC cell susceptibility to NK cell-mediated killing, suggesting that RocA enhanced NK cell-mediated killing through autophagy inhibition. Reference: Autophagy. 2018;14(10):1831-1844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135631/ |
| In vivo activity: | To evaluate the in vivo efficacy of Roc-A, a patient derived tumor xenografts (PDTX) model was established. SCID mice were subcutaneously injected pancreatic tumor cells from a patient and then treated with Roc-A or vehicle, which was administered intraperitoneally once per day. Without the xenograft, SCID mice tolerated Roc-A treatment at 1.5 mg/kg well, will all treated animals survived during the course of study without showing any noticeable signs of discomfort or loss of body weight (Figure 3A). Notably, patient-derived pancreatic tumor cells grew significantly slower in Roc-A treated animals as shown by reduced tumor volumes and the extended death curve (Figure 3B, 3C). All together, these data unambiguously demonstrated that Roc-A potently inhibited the growth of pancreatic tumor in vivo. Reference: Am J Transl Res. 2016 Feb 15;8(2):1047-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846947/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 80.0 | 158.24 | |
| Ethanol | 5.0 | 9.89 |
The following data is based on the product molecular weight 505.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Yao C, Ni Z, Gong C, Zhu X, Wang L, Xu Z, Zhou C, Li S, Zhou W, Zou C, Zhu S. Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy. Autophagy. 2018;14(10):1831-1844. doi: 10.1080/15548627.2018.1489946. Epub 2018 Aug 17. PMID: 29969944; PMCID: PMC6135631. 2. Wang B, Li Y, Tan F, Xiao Z. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells. Am J Transl Res. 2016 Feb 15;8(2):1047-54. PMID: 27158390; PMCID: PMC4846947. |
| In vitro protocol: | 1. Yao C, Ni Z, Gong C, Zhu X, Wang L, Xu Z, Zhou C, Li S, Zhou W, Zou C, Zhu S. Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy. Autophagy. 2018;14(10):1831-1844. doi: 10.1080/15548627.2018.1489946. Epub 2018 Aug 17. PMID: 29969944; PMCID: PMC6135631. 2. Wang B, Li Y, Tan F, Xiao Z. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells. Am J Transl Res. 2016 Feb 15;8(2):1047-54. PMID: 27158390; PMCID: PMC4846947. |
| In vivo protocol: | 1. Yao C, Ni Z, Gong C, Zhu X, Wang L, Xu Z, Zhou C, Li S, Zhou W, Zou C, Zhu S. Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy. Autophagy. 2018;14(10):1831-1844. doi: 10.1080/15548627.2018.1489946. Epub 2018 Aug 17. PMID: 29969944; PMCID: PMC6135631. 2. Wang B, Li Y, Tan F, Xiao Z. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells. Am J Transl Res. 2016 Feb 15;8(2):1047-54. PMID: 27158390; PMCID: PMC4846947. |
1: Luan Z, He Y, He F, Chen Z. 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. PubMed PMID: 25333816; PubMed Central PMCID: PMC4237083.
2: Duong NT, Edrada-Ebel R, Ebel R, Lin W, Duong AT, Dang XQ, Nguyen NH, Proksch P. New rocaglamide derivatives from Vietnamese Aglaia species. Nat Prod Commun. 2014 Jun;9(6):833-4. PubMed PMID: 25115092.
3: Pan L, Woodard JL, Lucas DM, Fuchs JR, Kinghorn AD. Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species. Nat Prod Rep. 2014 Jul;31(7):924-39. doi: 10.1039/c4np00006d. Epub 2014 May 2. Review. PubMed PMID: 24788392; PubMed Central PMCID: PMC4091845.
4: Becker MS, Schmezer P, Breuer R, Haas SF, Essers MA, Krammer PH, Li-Weber M. The traditional Chinese medical compound Rocaglamide protects nonmalignant primary cells from DNA damage-induced toxicity by inhibition of p53 expression. Cell Death Dis. 2014 Jan 16;5:e1000. doi: 10.1038/cddis.2013.528. PubMed PMID: 24434508; PubMed Central PMCID: PMC4040689.
5: Neumann J, Boerries M, Köhler R, Giaisi M, Krammer PH, Busch H, Li-Weber M. The natural anticancer compound rocaglamide selectively inhibits the G1-S-phase transition in cancer cells through the ATM/ATR-mediated Chk1/2 cell cycle checkpoints. Int J Cancer. 2014 Apr 15;134(8):1991-2002. doi: 10.1002/ijc.28521. Epub 2013 Oct 21. PubMed PMID: 24150948.
6: El-Neketi M, Ebrahim W, Duong NT, Gedara S, Badria F, Saad HE, Müller WE, Proksch P. Cytotoxic rocaglamide derivatives from Aglaia duppereana. Z Naturforsch C. 2013 Jul-Aug;68(7-8):269-74. PubMed PMID: 24066511.
7: Sadlish H, Galicia-Vazquez G, Paris CG, Aust T, Bhullar B, Chang L, Helliwell SB, Hoepfner D, Knapp B, Riedl R, Roggo S, Schuierer S, Studer C, Porco JA Jr, Pelletier J, Movva NR. Evidence for a functionally relevant rocaglamide binding site on the eIF4A-RNA complex. ACS Chem Biol. 2013 Jul 19;8(7):1519-27. doi: 10.1021/cb400158t. Epub 2013 May 7. PubMed PMID: 23614532; PubMed Central PMCID: PMC3796129.
8: Malona JA, Cariou K, Spencer WT 3rd, Frontier AJ. Total synthesis of (±)-rocaglamide via oxidation-initiated Nazarov cyclization. J Org Chem. 2012 Feb 17;77(4):1891-908. doi: 10.1021/jo202366c. Epub 2012 Jan 26. PubMed PMID: 22283818; PubMed Central PMCID: PMC3306619.
9: Rodrigo CM, Cencic R, Roche SP, Pelletier J, Porco JA. Synthesis of rocaglamide hydroxamates and related compounds as eukaryotic translation inhibitors: synthetic and biological studies. J Med Chem. 2012 Jan 12;55(1):558-62. doi: 10.1021/jm201263k. Epub 2011 Dec 19. PubMed PMID: 22128783; PubMed Central PMCID: PMC3263355.
10: Giaisi M, Köhler R, Fulda S, Krammer PH, Li-Weber M. 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. PubMed PMID: 21952919.
11: Cai XH, Xie B, Guo H. Progress in the total synthesis of rocaglamide. ISRN Org Chem. 2011 Apr 4;2011:239817. doi: 10.5402/2011/239817. Review. PubMed PMID: 24052818; PubMed Central PMCID: PMC3767207.
12: Bleumink M, Köhler R, Giaisi M, Proksch P, Krammer PH, Li-Weber M. Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia/lymphoma by translational suppression of c-FLIP expression. Cell Death Differ. 2011 Feb;18(2):362-70. doi: 10.1038/cdd.2010.99. Epub 2010 Aug 13. PubMed PMID: 20706274; PubMed Central PMCID: PMC3131883.
13: Malona JA, Cariou K, Frontier AJ. Nazarov cyclization initiated by peracid oxidation: the total synthesis of (+/-)-rocaglamide. J Am Chem Soc. 2009 Jun 10;131(22):7560-1. doi: 10.1021/ja9029736. PubMed PMID: 19445456; PubMed Central PMCID: PMC2732401.
14: Zhu JY, Giaisi M, Köhler R, Müller WW, Mühleisen A, Proksch P, Krammer PH, Li-Weber M. Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression. Cell Death Differ. 2009 Sep;16(9):1289-99. doi: 10.1038/cdd.2009.42. Epub 2009 Apr 17. PubMed PMID: 19373244.
15: Giese MW, Moser WH. Stereoselective synthesis of the rocaglamide skeleton via a silyl vinylketene formation/[4 + 1] annulation sequence. Org Lett. 2008 Oct 2;10(19):4215-8. doi: 10.1021/ol801435j. Epub 2008 Aug 28. PubMed PMID: 18754622.
16: Zhu JY, Lavrik IN, Mahlknecht U, Giaisi M, Proksch P, Krammer PH, Li-Weber M. The traditional Chinese herbal compound rocaglamide preferentially induces apoptosis in leukemia cells by modulation of mitogen-activated protein kinase activities. Int J Cancer. 2007 Oct 15;121(8):1839-46. PubMed PMID: 17565740.
17: Chumkaew P, Kato S, Chantrapromma K. Potent cytotoxic rocaglamide derivatives from the fruits of Amoora cucullata. Chem Pharm Bull (Tokyo). 2006 Sep;54(9):1344-6. PubMed PMID: 16946551.
18: Proksch P, Giaisi M, Treiber MK, Palfi K, Merling A, Spring H, Krammer PH, Li-Weber M. Rocaglamide derivatives are immunosuppressive phytochemicals that target NF-AT activity in T cells. J Immunol. 2005 Jun 1;174(11):7075-84. PubMed PMID: 15905551.
19: Bringmann G, Mühlbacher J, Messer K, Dreyer M, Ebel R, Nugroho BW, Wray V, Proksch P. Cyclorocaglamide, the first bridged cyclopentatetrahydrobenzofuran, and a related "open chain" rocaglamide derivative from Aglaia oligophylla. J Nat Prod. 2003 Jan;66(1):80-5. PubMed PMID: 12542350.
20: Baumann B, Bohnenstengel F, Siegmund D, Wajant H, Weber C, Herr I, Debatin KM, Proksch P, Wirth T. Rocaglamide derivatives are potent inhibitors of NF-kappa B activation in T-cells. J Biol Chem. 2002 Nov 22;277(47):44791-800. Epub 2002 Sep 16. PubMed PMID: 12237314.
