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Synonyms | CBLC137 HCl, Curaxin 137 HCl | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C21H24N2O2.HCl |
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分子量 | 372.89 | CAS No. | 1197397-89-9 | |
Solubility (25°C)* | 体外 | DMSO | 20 mg/mL (53.63 mM) | |
Water | 20 mg/mL (53.63 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. |
製品説明 | 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). |
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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 orthotopic gemcitabine resistant PANC-1 model and 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]. |
細胞アッセイ | 細胞株 | tumor (HT1080, RCC45, MiaPaca) and normal cells (Wi38, NKE-hTERT) |
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濃度 | 2 μM | |
反応時間 | 24 h | |
実験の流れ | 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. |
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動物実験 | 動物モデル | xenograft mouse models of cancer (athymic nude mice) |
投薬量 | 30 mg/kg | |
投与方法 | by oral gavage |
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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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。