[CAS NO. 177262-30-5] Didesmethylrocaglamide
PRODUCTS SPECIFICATIONS [177262-30-5]
DESCRIPTION [177262-30-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 477.51 |
| Molecular Formula | C27H27NO7 |
| SMILES | 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 |
Summary
Didesmethylrocaglamide, a derivative of Rocaglamide, is a potent eukaryotic initiation factor 4A (eIF4A) inhibitor. Didesmethylrocaglamide has potent growth-inhibitory activity with an IC 50 of 5 nM. Didesmethylrocaglamide suppresses multiple growth-promoting signaling pathways and induces apoptosis in tumor cells. Antitumor activity [1] [2] .
IC50 & Target
Eukaryotic initiation factor 4A (eIF4A) [1]
In Vitro
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
[1]
.
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)
[1]
.
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
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 209.42 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0942 mL | 10.4710 mL | 20.9420 mL |
| 5 mM | 0.4188 mL | 2.0942 mL | 4.1884 mL |
| 10 mM | 0.2094 mL | 1.0471 mL | 2.0942 mL |
References
- [1] Long-Sheng Chang, et al. Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas. Mol Cancer Ther. 2020 Mar;19(3):731-741.
- [2] Long-Sheng Chang, et al. Abstract 1950: The eIF4A inhibitors didesmethylrocaglamide and rocaglamide as effective treatments for pediatric bone and soft-tissue sarcomas. Cancer Res 2020;80(16 Suppl):Abstract nr 1950.