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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
FACT; p53 (EC50 = 0.37 μM); NF-κB (EC50 = 0.47 μM)
CBL0137 targets the FACT (facilitates chromatin transcription) complex, a histone chaperone involved in chromatin remodeling and transcription elongation. Through functional inactivation of FACT, it drives p53 activation and NF-κB inhibition. FACT is overexpressed in various tumors, with pancreatic ductal adenocarcinoma having the highest rate of overexpression (59%) among several tumor types. |
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| ln Vitro |
At concentrations greater than 2.5 μM, treatment with CBL-0137 results in the complete absence of living cells. When combined with gemcitabine, CBL-0137 results in a greater decrease in the number of colonies formed by both gemcitabine-resistant PANC-1 cells and MiaPaCa-2 cells. RRM1 and RRM2 protein and mRNA levels are decreased in a dose-dependent manner by CBL-0137 treatment of human pancreatic cancer cells. Gemcitabine-induced expression of RRM1 and RRM2 on both the mRNA and protein levels can be stopped by CBL-0137[1].
In vitro, at concentrations greater than 2.5 μM, CBL0137 treatment results in complete absence of living cells. When combined with gemcitabine, CBL0137 causes a greater decrease in colony formation in both gemcitabine-resistant PANC-1 cells and MiaPaCa-2 cells. It decreases RRM1 and RRM2 protein and mRNA levels in a dose-dependent manner in human pancreatic cancer cells. |
| ln Vivo |
Large necrotic fields, numerous apoptotic bodies, and a loss of tumor cells are visible in the samples from the CBL-0137 monotherapy group and the CBL-0137-gemcitabine combination group. The lack of statistically significant differences between the combination groups suggests that sub-optimal doses of 50 to 60 mg/kg CBL-0137 enhance gemcitabine antitumor activity in a manner comparable to that produced by the maximum tolerated dose (MTD) of 90 mg/kg. By reducing the number of active FACT involved in transcription elongation, CBL0137 hydrochloride inhibits the function of FACT[1]. CBL-0137 inhibits tumor growth in xenografts of colon (DLD-1), renal cell carcinoma (Caki-1), and melanoma (Mel-7) tumor cell lines and transplanted surgical samples from patients with pancreatic ductal adenocarcinoma[2] when administered orally at a nontoxic dose of 30 mg/kg per day on a schedule of 5 days on/2 days off.
In vivo, CBL0137 monotherapy and combination with gemcitabine show large necrotic fields, numerous apoptotic bodies, and loss of tumor cells in xenograft samples. Sub-optimal doses of 50-60 mg/kg CBL0137 enhance gemcitabine antitumor activity comparable to the maximum tolerated dose of 90 mg/kg. Oral administration at 30 mg/kg/day (5 days on/2 days off) inhibits tumor growth in colon, renal cell carcinoma, and melanoma xenografts. |
| Enzyme Assay |
CBL-0137 is applied to MiaPaca2 and BxPC-3 cells for 4 or 24 hours. Protease and phosphatase inhibitors are present in 1×Cell Culture Lysis Reagent, which is used to harvest cells. Lysates 5 to 20 μg are transferred to PVDF membranes after being separated on SDS-PAGE gels. Antibodies that target the proteins SSRP1, SPT16, RRM1 and RRM2 are used to probe blots. The loading control is GAPDH. ECL kit is used to visualize proteins[1].
Cell-free assays for CBL0137 are not standard enzymatic assays, as it targets the FACT complex. Binding to FACT can be assessed using biophysical methods such as surface plasmon resonance or isothermal titration calorimetry with purified FACT components. Alternatively, chromatin-binding assays can evaluate the compound's effect on FACT association with chromatin in vitro. |
| Cell Assay |
Different concentrations of CBL-0137 are applied to the cells after they have been resuspended in serum-free Dulbecco's Modified Eagle Medium (DMEM) for 1 hour. Then, 105 cells from each treatment condition are plated in 3 wells of a 6-well plate in 2 mL of serum-free DMEM/F12 medium supplemented with 0.4% BSA, 0.2×B27, 10 ng/mL recombinant EGF, and containing 0.25% agarose. A 6-well plate with 3 wells of regular FBS-containing medium is used to plate 103 cells from each treatment condition. After plating, seven to fifteen days later, colonies are counted using an inverted microscope[1].
CBL0137 is applied to pancreatic cancer cell lines such as MiaPaca2 and BxPC-3 cells for 4 hours to assess its effects. Cell viability is measured using MTT or colony formation assays. The activation of p53 and inhibition of NF-κB are evaluated using reporter gene assays or by measuring downstream target gene expression. |
| Animal Protocol |
Ketamine/xylazine is used to produce a deep anesthesia in 10-week-old female athymic nude mice (n=8 per treatment group). 2× 106 PANC-1 cells are injected into each mouse's pancreas tail via laparotomy. Treatment started two weeks after the vaccination (ultrasound confirmed the presence of the tumor). The following schedules are employed: 1) Vehicles, gavaged sterile water and 100mg/kg captisol intravenously, 2) once weekly intravenous administration of 50 to 90 mg/kg CBL-0137 in 100 mg/mL captisol, 3) 5 days on, 2 days off oral gavage administration of 10 to 20 mg/kg of CBL-0137. Utilizing digital calipers, tumors are measured. Using the formula L×W2/2, the tumor volume is calculated, where L is the longest dimension and W is the dimension perpendicular to L. Mice are observed until either 90 days have passed since the start of treatment or at least one tumor per mouse has reached 1000 mm3[1].
In vivo studies use xenograft models of colon cancer (DLD-1), renal cell carcinoma (Caki-1), melanoma (Mel-7), and patient-derived pancreatic ductal adenocarcinoma samples. CBL0137 is administered orally at 30 mg/kg/day on a 5 days on/2 days off schedule. Tumor growth inhibition, apoptosis, and necrosis are assessed histologically. |
| ADME/Pharmacokinetics |
CBL0137 has the molecular formula C₂₁H₂₄N₂O₂. It is metabolically stable. The compound is orally bioavailable, as demonstrated by its efficacy in oral dosing studies. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability are not fully disclosed in the available literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data are detailed in the provided references. However, the compound has been evaluated in preclinical models with non-toxic doses (30 mg/kg/day) showing efficacy. As a FACT inhibitor, potential toxicities would be related to disruption of chromatin remodeling in normal cells, but the compound has progressed to clinical testing in glioblastoma and hematological malignancies.
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| References |
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| Additional Infomation |
CBL0137 belongs to the carbazole class of compounds, with the structure 9H-carbazole, substituted with acetyl groups at positions 3 and 6, and substituted with 2-isopropylethyl at position 9 (nitrogen atom). It is a regulator of the histone chaperone FACT (chromatin transcription promoting factor)—the interaction between CBL0137 and the FACT complex can simultaneously inhibit NF-κB, heat shock transcription factor 1 (HSF1), and activate p53—and has shown anti-tumor effects in various animal models of cancer. It possesses multiple functions, including NF-κB inhibitor, p53 activator, anti-tumor agent, and apoptosis inducer. It belongs to the carbazole class, secondary amine class, tertiary amine class, aromatic ketone class, and methyl ketone class of compounds.
CBL0137 (also known as Curaxin 137) is an investigational compound not yet approved for clinical use. It is currently being tested in clinical trials for glioblastoma and hematological malignancies. In pancreatic cancer preclinical models, CBL0137 eliminates drug-resistant cancer stem cells and enhances the effectiveness of gemcitabine. |
| Molecular Formula |
C21H24N2O2
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|---|---|
| Molecular Weight |
336.44
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| Exact Mass |
336.184
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| Elemental Analysis |
C, 74.97; H, 7.19; N, 8.33; O, 9.51
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| CAS # |
1197996-80-7
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| Related CAS # |
CBL0137 hydrochloride;1197397-89-9
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| PubChem CID |
44519124
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.588
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
466
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)NCCN1C2=C(C=C(C=C2)C(=O)C)C3=C1C=CC(=C3)C(=O)C
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| InChi Key |
JKCSODVERGVDLT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24N2O2/c1-13(2)22-9-10-23-20-7-5-16(14(3)24)11-18(20)19-12-17(15(4)25)6-8-21(19)23/h5-8,11-13,22H,9-10H2,1-4H3
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| Chemical Name |
1-[6-acetyl-9-[2-(propan-2-ylamino)ethyl]carbazol-3-yl]ethanone
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| Synonyms |
CBL0137; CBL 0137; CBL-0137; CBLC-137; CBLC137; Curaxin 137; CBL-0137 free base; CBL-0137; CBL 0137; 8XKR07H9ER; CBL 137; Curaxin 137; CHEMBL4640631; CBLC 137
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.11 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (11.1 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.11 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (11.1 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.11 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (11.1 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9723 mL | 14.8615 mL | 29.7230 mL | |
| 5 mM | 0.5945 mL | 2.9723 mL | 5.9446 mL | |
| 10 mM | 0.2972 mL | 1.4861 mL | 2.9723 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05498792 | Recruiting | Drug: CBL0137 Drug: Ipilimumab |
Locally Advanced or Metastatic Melanoma |
Fox Chase Cancer Center | November 30, 2022 | Early Phase 1 |
| NCT01373554 | Recruiting | Drug: FACT Complex-targeting Curaxin CBL0137 |
Recurrent Sarcoma of the Extremity Advanced Sarcoma of the Extremity |
Roswell Park Cancer Institute | July 1, 2019 | Phase 1 |
| NCT01905228 | Completed | Drug: CBL0137 | Solid Tumors Glioblastoma |
Incuron | July 2013 | Phase 1 |
 CBL0137 and gemcitabine toxicity to pancreatic ductal adenocarcinoma cell lines.Oncotarget.2014 Nov 30;5(22):11038-53. |
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Effect of CBL0137 and gemcitabine on orthotopic PANC1 pancreatic tumor growth in nude mice.Oncotarget.2014 Nov 30;5(22):11038-53. |
 Morphology and expression of FACT subunits (SSRP1, SPT16) and proliferation marker Ki67 in PDX samples of pancreatic ductal adenocarcinoma (PDA) used in the study.Oncotarget.2014 Nov 30;5(22):11038-53. |
 Effect of CBL0137 and gemcitabine on patient derived PDA xenograft models.Oncotarget.2014 Nov 30;5(22):11038-53. |
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 CBL0137 inhibit gemcitabine induced transcriptional responses.Oncotarget.2014 Nov 30;5(22):11038-53. |
 CBL0137 is toxic for cancer stem cells (CSC).Oncotarget.2014 Nov 30;5(22):11038-53. |
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