Structure of CBL0137 HCl
CAS No.: 1197397-89-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Target |
|
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 |
Tags: CBL0137 | Curaxin-137 | CBL-C137 | CBL 0137 | CBL-0137 | Curaxin137 | Curaxin 137 | MDM-2/p53 | NF-κB | Nuclear factor-κB | Nuclear factor-kappaB | histone chaperone | FACT Inhibitor | p53 activation | NF-κB Inhibitor | Nuclear factor-κB | Nuclear factor-kappaB | Nuclear Factor kappa-light-chain-enhancer of activated B cells | NFKB | NF-KB | transcription factor | inflammation | cell proliferation | apoptosis | immune response | 1197397-89-9
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