aladdin 阿拉丁 C408753 CBL0137 HCl 1197397-89-9 10mM in DMSO

中文名：CBL0137盐酸

英文名：CBL0137 HCl

纯度：≥99%

货号：C414023

Cas号：1197397-89-9

存储温度：-20°C储存

运输条件：超低温运输

产品介绍：

Information

CBL0137 HCl CBL0137 (CBLC137, Curaxin 137) HCl activates p53 and inhibits NF-kB with EC50s of 0.37 μM and 0.47 μM in the cell-based p53 and NF-kB reporter assays, respectively. It also inhibits histone chaperone FACT (facilitates chromatin transcription complex).

Targets

FACT ; p53 (Cell-free assay); NF-κB (Cell-free assay) ; 0.37 μM(EC50); 0.47 μM(EC50)

In vitro

CBL0137 is a potent inducer of apoptosis in pancreatic cancer cell lines and is toxic not only for proliferating bulk tumor cells, but also for pancreatic cancer stem cells. CBL0137 and related molecules can simultaneously activate p53 and inhibit cellular stress pathways mediated by NF-κB and HSF-1. CBL0137 binds DNA but does not cause any sort of chemical modifications in DNA and therefore lacks genotoxicity. However, CBL0137 binding to DNA leads to functional inactivation of the Facilitates Chromatin Transcription (FACT) complex, a chromatin remodeling complex involved in transcription, replication, and DNA repair. In CBL0137-treated cells, FACT is lost from the nucleoplasm and trapped in chromatin, resulting in the inhibition of FACT-dependent transcription, including NF-kB-mediated transcription. Additionally, chromatin trapping of FACT leads to casein kinase 2 (CK2)-dependent phosphorylation and activation of p53.

In vivo

In mice, CBL0137 is effective against several Pancreatic ductal adenocarcinoma (PDA) models, including orthotopic gemcitabine resistant PANC-1 model and patient derived xenografts, in which CBL0137 anti-tumor effect correlated with overexpression of FACT. CBL0137 targets glioblastoma (GBM) according to its proposed mechanism of action, crosses the blood-brain barrier, and is efficacious in both TMZ-responsive and -resistant orthotopic models. The property of crossing the blood-brain barrier, especially when administered i.v, bodes well for the potential of this drug to treat CNS tumors. In orthotopic models, i.v. administration leads to greater tumor tissue accumulation than oral dosing, leading to greater bioavailability. Normal brain tissue accumulation of CBL0137 does not cause observable neurotoxicity.

Cell Research(from reference)

Cell lines：tumor (HT1080, RCC45, MiaPaca) and normal cells (Wi38, NKE-hTERT) 

Concentrations：2 μM 

Incubation Time：24 h 

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