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Chemical Structure| 1197397-89-9 Chemical Structure| 1197397-89-9

Structure of CBL0137 HCl
CAS No.: 1197397-89-9

Chemical Structure| 1197397-89-9

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CBL0137 HCl is a metabolically stable curaxin that activates p53 with an EC50 value of 0.37 µM and inhibits NF-κB with an EC50 of 0.47 µM.

Synonyms: CBL-C137 hydrochloride; Curaxin-137 hydrochloride; Curaxin 137

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Product Details of CBL0137 HCl

CAS No. :1197397-89-9
Formula : C21H25ClN2O2
M.W : 372.89
SMILES Code : CC(NCCN1C2=C(C3=C1C=CC(C(C)=O)=C3)C=C(C(C)=O)C=C2)C.[H]Cl
Synonyms :
CBL-C137 hydrochloride; Curaxin-137 hydrochloride; Curaxin 137
MDL No. :MFCD28160457
InChI Key :IXRKBBVMDMKAEB-UHFFFAOYSA-N
Pubchem ID :44519123

Safety of CBL0137 HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of CBL0137 HCl

pyroptosis

Isoform Comparison

Biological Activity

Target
  • NF-κB

    NF-κB, EC50:0.47 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
Human Fibroblasts (HS68) 5 μM 36 hours CBL0137 induces ZBP1-dependent cell death in hIFNβ-pretreated HS68 cells. PMC9373927
Murine Embryonic Fibroblasts (MEFs) 5 μM 24 hours CBL0137 activates ZBP1-dependent cell death, including necroptosis and apoptosis, by inducing Z-DNA formation. PMC9373927
NK-92 cells 500 nM 24 hours CBL0137 treatment upregulated the expression of IFNs and ISGs, and enhanced NK cell-mediated killing of virus-infected cells. PMC9410884
HeLa cells 100, 200, 500 nM 24 hours To evaluate the ability of BSA–RuII(CO)2 complex to release CO in HeLa cells, results showed a significant increase in intracellular fluorescence indicating CO release. PMC9410884
HEK293T cells 100, 200, 500 nM 24 hours To evaluate the effect of ACBI1 on SMARCA4 protein levels in HEK293T cells, results showed that ACBI1 treatment led to a reduction in SMARCA4 protein levels. PMC9410884
BJ fibroblasts 1 μM 3 hours Induced degradation of POLR2A but no degradation of POLR1A was observed. PMC11077059
U2OS cells 1 μM 3 hours Significantly inhibited U2OS cell growth PMC11077059
NDF cells 1 μM 24 hours To evaluate the toxicity of CBL0137 on normal fibroblasts and p53 activation. Results showed that CBL0137 caused growth arrest at 0.5-1 μM but did not induce senescence markers. PMC10681726
HT1080 cells 1 μM 24 hours To evaluate the toxicity of CBL0137 on HT1080 cells and p53 activation. Results showed that CBL0137 caused growth arrest at 0.5-1 μM but did not induce senescence markers. PMC10681726
A1207 0.6 or 2.0 µM 1 or 16 hours Evaluate the effect of CBL0137 on FACT, p53, and NF-ĸB. Results showed that CBL0137 caused loss of FACT subunits from the soluble protein fraction, significantly increased p53 expression, and inhibited NF-ĸB-dependent transcription. PMC5604960
U87MG 0.6 or 2.0 µM 1 or 16 hours Evaluate the effect of CBL0137 on FACT, p53, and NF-ĸB. Results showed that CBL0137 caused loss of FACT subunits from the soluble protein fraction, significantly increased p53 expression, and inhibited NF-ĸB-dependent transcription. PMC5604960
B16 NF-κB-Luc reporter cells 5 or 10 μM 15 minutes To assess the effect of CBL0137 on NF-κB pathway activity, results showed that CBL0137 dose-dependently suppressed NF-κB pathway activity. PMC5609527
B16 melanoma cells 0.7, 1.4, 2.8, or 5.6 μM 15 or 30 minutes To evaluate the cytotoxic effects of CBL0137 on B16 melanoma cells, results showed that CBL0137 significantly reduced cell viability after 15 and 30 minutes of treatment. PMC5609527
BE(2)C cells 100 nM 22 hours Evaluate the effect of CBL0137 on DNA double-strand break repair PMC6207083
HT1080 3 μM 1.5 hours Study the effect of CBL0137 on FACT chromatin binding via ChIP-seq analysis PMC5856628
HeLa 0.6 μM 48 hours PMC5856628
Non-stem tumor cells (CD133-) 100–600 nM 72 hours Evaluate the inhibitory effect of CBL0137 on non-stem tumor cells, results showed that CBL0137 effectively inhibited the proliferation of non-stem tumor cells. PMC4873320
GBM stem cells (CD133+) 100–600 nM 72 hours Evaluate the inhibitory effect of CBL0137 on GBM stem cells, results showed that CBL0137 effectively inhibited the proliferation of GBM stem cells. PMC4873320
HT1080 cells 3 μM To evaluate the toxicity of CBL0137 on HT1080 cells and p53 activation. Results showed that CBL0137 caused growth arrest at 0.5-1 μM but did not induce senescence markers. PMC6221510

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice (C57BL/6J) B16-F10 melanoma model Intratumoral injection 20 μM (intratumoral injection) Every two days for a total of 4 doses CBL0137 significantly enhances the therapeutic effect of anti-PD-1 antibody by inducing ZBP1-dependent necroptosis in fibroblasts of the tumor microenvironment (TME). PMC9373927
Nude mice Breast cancer model Oral gavage 30 mg/kg Five days a week for six weeks CBL0137 inhibited the growth of TMD-436 cells-derived tumors but TMD-231 cell-derived tumors were resistant to the treatment PMC10107402
Nude mice U87MG and A1207 orthotopic glioblastoma models Oral or intravenous 25 mg/kg orally or 70 mg/kg intravenously Daily oral for 8 days or weekly intravenous twice Evaluate the antitumor effect of CBL0137 in vivo. Results showed that intravenous administration of CBL0137 significantly increased survival and accumulated more in tumor tissue than in normal brain tissue. PMC5604960
C57BL/6 mice B16 melanoma model Isolated limb perfusion (ILP) or intra-arterial infusion (IAI) 0.044, 0.111, 0.222, and 0.444 mg/mL (15-minute perfusion) or 0.022, 0.055, 0.111 and 0.222 mg/mL (30-minute perfusion) Single 15 or 30-minute perfusion To evaluate the antitumor efficacy of CBL0137 in vivo against melanoma, results showed that CBL0137 administered via ILP or IAI significantly suppressed tumor growth and was more effective than systemic administration. PMC5609527
Mice TH-MYCN+/+ mice Intravenous 60 mg/kg Every 4 days for 8 doses Evaluate the therapeutic effect of CBL0137 on established neuroblastoma PMC6207083
NSG mice Orthotopic GBM model Oral administration 0.5 mg/mL Replaced every 7 days, continuous treatment Evaluate the therapeutic effect of CBL0137 on orthotopic GBM model, results showed that CBL0137 significantly prolonged the survival of mice. PMC4873320

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.68mL

0.54mL

0.27mL

13.41mL

2.68mL

1.34mL

26.82mL

5.36mL

2.68mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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