CBL0137 HCl

Catalog No.S8483 Synonyms: CBLC137 HCl, Curaxin 137 HCl

For research use only.

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).

CBL0137 HCl Chemical Structure

CAS No. 1197397-89-9

Selleck's CBL0137 HCl has been cited by 5 Publications

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Biological Activity

Description 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 [1]
()
p53 [1]
(Cell-free assay)
NF-κB [1]
(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[2]. 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[3].

Assay
Methods Test Index PMID
Western blot p53 / Hdm2 ; caspase-3 / caspase-7 / caspase-8 / caspase-9 / PARP 27370399 25402820
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[1]. 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[3].

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: tumor (HT1080, RCC45, MiaPaca) and normal cells (Wi38, NKE-hTERT)
  • Concentrations: 2 μM
  • Incubation Time: 24 h
  • Method:

    Effects of CBLC137 (2 μM for 24 hours) on cell cycle in tumor (HT1080, RCC45, MiaPaca) and normal cells (Wi38, NKE-hTERT) are examined using FACS analysis of propidium iodide-stained cells.

Animal Research:

[1]

  • Animal Models: xenograft mouse models of cancer (athymic nude mice)
  • Dosages: 30 mg/kg
  • Administration: by oral gavage

Solubility (25°C)

In vitro

DMSO 38 mg/mL
(101.9 mM)
Water 24 mg/mL
(64.36 mM)
Ethanol Insoluble

Chemical Information

Molecular Weight 372.89
Formula

C21H24N2O2.HCl

CAS No. 1197397-89-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)NCCN1C2=C(C=C(C=C2)C(=O)C)C3=C1C=CC(=C3)C(=O)C.Cl

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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