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Purity: ≥98%
CBL0137 (formerly known as Curaxin 137 or CBL-0137) is an inhibitor of the histone chaperone, FACT (facilitates chromatin transcription complex). Additionally, in cell-based assays for p53 and NF-kB reporter, it activates p53 and inhibits NF-kB with EC50s of 0.37 μM and 0.47 μM, respectively. Glioblastoma and hematological malignancies are the two conditions CBL0137 is currently being tested for. In pancreatic cancer preclinical models, CBL0137 eliminates drug-resistant cancer stem cells and enhances the effectiveness of gemcitabine. Through the inhibition of chromatin remodeling complex FACT, curaxins regulate a number of significant signaling pathways involved in the pathogenesis of pancreatic ductal adenocarcinoma (PDA). With PDA having the highest rate of overexpression (59%) among several tumor types, FACT is overexpressed.
| Targets |
FACT; p53 (EC50 = 0.37 μM); NF-κB (EC50 = 0.47 μM)
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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].
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| 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.
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| 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].
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| 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].
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| 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].
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| References |
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| Additional Infomation |
CBL0137 is a member of the class of carbazoles that is 9H-carbazole which is substituted by acetyl groups at positions 3 and 6, and by a 2-isopropylethyl group on the nitrogen atom (position 9). It is a modulator of histone chaperone FACT (FAcilitates Chromatin Transcription) - interaction of CBL0137 with the FACT complex results in simultaneous NF-kappa beta suppression, Heat Shock Transcription Factor 1 (HSF1) suppression and p53 activation - and shows antitumour effects in animal models of various cancers. It has a role as a NF-kappaB inhibitor, a p53 activator, an antineoplastic agent and an apoptosis inducer. It is a member of carbazoles, a secondary amino compound, a tertiary amino compound, an aromatic ketone and a methyl ketone.
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| 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 |
| 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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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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