CR-1-31-B is a synthetic rocaglate and a potent eIF4A inhibitor. CR-1-31-B exhibits powerful inhibitory effects over eIF4A by perturbing the interaction between eIF4A and RNA, sequentially impeding initiation during protein synthesis. CR-1-31-B perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31-B induces apoptosis of neuroblastoma and gallbladder cancer cells[1][2][3][4].
体外研究 (In Vitro)
CR-1-31-B (100 nM; 24 hours) inhibits MUC1-C translation in MCF-10A cells (EGF-stimulated)[1]. CR-1-31-B (10 and 100 nM) decreases MUC1-C abundance in MDA-MB-468 breast cancer cells[1]. CR-1-31B sensitizes gallbladder cancer cells to TRAIL-mediated apoptosis through the translational downregulation of c-FLIP[2]. Neuroblastoma (NB) cell lines exhibit decreased viability, increased apoptosis rates as well as changes in cell cycle distribution when treated with the synthetic rocaglate CR-1-31-B (24-72 hours), which clamps eIF4A and eIF4F onto mRNA, resulting in a translational block[4]. CR-1-31-B (100 nM; 5 hours) treatment increases reverse glutamine metabolism in pancreatic cancer cells[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
MCF-10A cells (EGF-stimulated)
Concentration:
100 nM
Incubation Time:
24 hours
Result:
Blocked increases in MUC1-C abundance.
Cell Viability Assay[4]
Cell Line:
SH-SY5Y cells and Kelly cells
Concentration:
0.1-100 nM
Incubation Time:
24-72 hours
Result:
A significant decrease in SH-SY5Y viability was observed at 10 nM for all time points. Significantly decreased the viability of Kelly cells at 5 nM. The calculated IC50 at 48 h was 20 nM for SH-SY5Y and 4 nM for Kelly cells.
Apoptosis Analysis[4]
Cell Line:
SH-SY5Y and Kelly cells
Concentration:
SH-SY5Y cells were treated with 10, 20, and 50 nM and Kelly cells with 1, 5, and 10 nM
Incubation Time:
24-72 hours
Result:
Triggered apoptosis.
体内研究 (In Vivo)
CR-1-31-B (2 mg/kg in 60 µL olive oil; IP; once every 2 days for 28 days) reduces the growth and initiates TRAIL-induced apoptosis in a BALB/c nude mice model of gallbladder cancer cells (GBC)[2]. CR-1-31-B (0.2 mg/kg; IP; daily for 7 days; murine orthotopic transplant model of pancreatic ductal adenocarcinoma) effectively inhibits protein synthesis and growth of pancreatic tumours[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
507.53
Formula
C28H29NO8
CAS 号
1352914-52-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Jin C, Rajabi H, Rodrigo CM, Porco JA Jr, Kufe D. Targeting the eIF4A RNA helicase blocks translation of the MUC1-C oncoprotein. Oncogene. 2013;32(17):2179-2188.
[2]. Cao Y, et al. Targeting eIF4A using rocaglate CR 1 31B sensitizes gallbladder cancer cells to TRAIL mediated apoptosis through the translational downregulation of c FLIP. Oncol Rep. 2021;45(1):230-238.
[3]. Langlais D, et al. Rocaglates as dual-targeting agents for experimental cerebral malaria. Proc Natl Acad Sci U S A. 2018;115(10):E2366-E2375.
[4]. Skofler C, et al. Eukaryotic Translation Initiation Factor 4AI: A Potential Novel Target in Neuroblastoma. Cells. 2021;10(2):301. Published 2021 Feb 2.
[5]. Chan K, et al. eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma. Nat Commun. 2019;10(1):5151. Published 2019 Nov 13.
