CBL0137 HCl

Catalog No.S8483 Batch:S848301

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Technical Data

Formula

C21H24N2O2.HCl
Molecular Weight 372.89 CAS No. 1197397-89-9
Solubility (25°C)* In vitro DMSO 38 mg/mL (101.9 mM)
Water 24 mg/mL (64.36 mM)
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description CBL0137 (CBLC137, Curaxin 137) HCl activates p53 and inhibits NF-κB 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].
In vivo

In mice, CBL0137 is effective against several Pancreatic ductal adenocarcinoma (PDA) models, including 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 Assay:

[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 Study:

[1]
  • Animal Models

    xenograft mouse models of cancer (athymic nude mice)

  • Dosages

    30 mg/kg

  • Administration

    by oral gavage

Selleck's CBL0137 HCl has been cited by 8 publications

SETD2 regulates chromatin accessibility and transcription to suppress lung tumorigenesis [ JCI Insight, 2023, 8(4)e154120] PubMed: 36810256
CBL0137 impairs homologous recombination repair and sensitizes high-grade serous ovarian carcinoma to PARP inhibitors [ J Exp Clin Cancer Res, 2022, 41(1):355] PubMed: 36539830
Histone chaperone FACT complex inhibitor CBL0137 interferes with DNA damage repair and enhances sensitivity of medulloblastoma to chemotherapy and radiation [ Cancer Lett, 2021, 520:201-212] PubMed: 34271103
The small molecule drug CBL0137 increases the level of DNA damage and the efficacy of radiotherapy for glioblastoma [ Cancer Lett, 2021, 499:232-242] PubMed: 33253788
Inversion of asymmetric histone deposition upon replication stress [ bioRxiv, 2021, 10.1101/2021.04.20.440573] PubMed: None
MYC Controls the Epstein-Barr Virus Lytic Switch. [ Mol Cell, 2020, S1097-2765(20)30193-3] PubMed: 32315601
The small molecule drug CBL0137 increases the level of DNA damage and the efficacy of radiotherapy for glioblastoma [ Cancer Lett, 2020, S0304-3835(20)30624-8] PubMed: 33253788
Chromatin Trapping of Factors Involved in DNA Replication and Repair Underlies Heat-Induced Radio- and Chemosensitization [ Cells, 2020, 9(6):1423] PubMed: 32521766

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.