CBL0137 (hydrochloride)
(Synonyms: CBL0137盐酸盐,CBLC137,Curaxin 137) 目录号 : GC15394
CBL0137 (hydrochloride)是一种来自curaxins小分子家族的水溶性且代谢稳定的非遗传毒性抗癌药物，可以激活p53并抑制NF-κB，EC50值分别为0.37和0.47μM。
Cas No.:1197397-89-9
Sample solution is provided at 25 µL, 10mM.
CBL0137 (hydrochloride) is a water-soluble and metabolically stable non-genotoxic anticancer drug from the curaxins small molecule family. It can activate p53 and inhibit NF-κB, with EC50 values of 0.37 and 0.47μM respectively [1-2]. CBL0137 is an inhibitor of the histone molecular chaperone (FACT), which promotes the formation of chromatin transcription complexes and participates in the regulation of gene expression [3]. CBL0137 has anti-tumor activity and can enhance the therapeutic effect of chemotherapeutic drugs [4-5].
In vitro, CBL0137 (0.5, 1.0, 1.5 and 2.0μM; 24, 48 and 72h) significantly inhibits the proliferation of B-NHL cells in a concentration and time-dependent manner. Moreover, CBL0137 induces S-phase B-NHL cell cycle arrest by regulating the c-MYC/p53/21 pathway [6]. Different concentrations of CBL0137 (0-1μM; 24h) treatment significantly reduces the cell viability of NKTCL cell lines (RMA, SNT16 and NKYS) in a dose-dependent manner, with IC50 values of 0.71μM, 0.49μM and 0.50μM, respectively [7].
In vivo, CBL0137 (15mg/kg/day; 6 days; i.p.) treatment significantly inhibits tumor growth in RMA tumor-bearing mice, and the combined use with anti-PD-1 is more effective than single treatment [7]. CBL0137 (15mg/kg/day; once every three days, for a total of 14 days; i.p.) and rituximab combined treatment has a significantly enhanced anti-tumor effect in B-NHL tumor xenograft model mice, with increased tumor tissue necrosis area, decreased Ki67 expression level, and significantly increased caspase-3 and LC3B expression [6].
References:
[1] Jin M Z, Xia B R, Xu Y, et al. Curaxin CBL0137 exerts anticancer activity via diverse mechanisms[J]. Frontiers in oncology, 2018, 8: 598.
[2] Gasparian AV, Burkhart CA, Purmal AA, et al. Curaxins: anticancer compounds that simultaneously suppress NF-κB and activate p53 by targeting FACT. Sci Transl Med. 2011;3(95):95ra74.
[3] Song H, Xi S, Chen Y, et al. Histone chaperone FACT complex inhibitor CBL0137 interferes with DNA damage repair and enhances sensitivity of medulloblastoma to chemotherapy and radiation[J]. Cancer letters, 2021, 520: 201-212.
[4] Burkhart, C., Fleyshman, D., Kohrn, R., et al. Curaxin CBL0137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer. Oncotarget 5(22),11038-11053 (2014).
[5] De S, Lindner D J, Coleman C J, et al. The FACT inhibitor CBL0137 synergizes with cisplatin in small-cell lung cancer by increasing NOTCH1 expression and targeting tumor-initiating cells[J]. Cancer Research, 2018, 78(9): 2396-2406.
[6] Lv Y, Du Y, Li K, et al. The FACT-targeted drug CBL0137 enhances the effects of rituximab to inhibit B-cell non-Hodgkin’s lymphoma tumor growth by promoting apoptosis and autophagy[J]. Cell Communication and Signaling, 2023, 21(1): 16.
[7] Gu H, Qian S, Zhang Y, et al. The small molecule drug CBL0137 interferes with DNA damage repair and enhances the sensitivity of NK/T-Cell lymphoma to cisplatin[J]. Cancer Biology & Therapy, 2025, 26(1): 2511301.
CBL0137 (hydrochloride)是一种来自curaxins小分子家族的水溶性且代谢稳定的非遗传毒性抗癌药物，可以激活p53并抑制NF-κB，EC50值分别为0.37和0.47μM [1-2]。CBL0137是一种组蛋白分子伴侣（FACT）的抑制剂，FACT能促进染色质转录复合体的形成，参与基因表达的调控过程 [3] 。CBL0137具有抗肿瘤活性并能增强化疗药的治疗效果 [4-5]。
在体外，CBL0137（0.5, 1.0, 1.5和2.0μM; 24, 48和72h）以浓度和时间依赖性方式显著抑制B-NHL细胞增殖。并且CBL0137通过调节c-MYC/p53/21通路诱导S期B-NHL细胞周期停滞 [6]。不同浓度的CBL0137（0-1μM; 24h）处理以剂量依赖性方式显著降低NKTCL细胞系（RMA、SNT16和NKYS）的细胞活力，IC50分别为0.71μM、0.49μM和0.50μM [7]。
在体内，CBL0137（15mg/kg/day; 6 days; i.p.）治疗显著抑制了RMA荷瘤小鼠的肿瘤生长，并且与抗 PD-1联合使用比单独治疗效果更好 [7]。CBL0137（15mg/kg/day; 每三天一次，总共持续 14 天; i.p.）和rituximab联合治疗在B-NHL荷瘤异种移植模型小鼠中具有显著增强的抗肿瘤作用，肿瘤组织坏死面积增加，Ki67表达水平下降，并且caspase-3和LC3B表达显著增加 [6]。
| Cell experiment [1]: | |
Cell lines | B-NHL cells |
Preparation Method | B-NHL cells were mixed with an equal volume of methylcellulose colony assay medium, plated in 12-well plates, and incubated for two weeks. For cell cycle analysis, B-NHL cells were treated with CBL0137 (0.5μM, 1.0μM, 1.5μM, and 2.0μM) for 24h and stained with PI/RNase for 30min. An Annexin V-FITC/PI Apoptosis Kit from Vazyme was used for apoptosis analysis. Flow cytometry was used for detection, and the data were analyzed by FlowJo software. |
Reaction Conditions | 0.5, 1.0, 1.5 and 2.0μM; 24h |
Applications | As the concentration of CBL0137 increases, the population of G0/G1 phase cells in B-NHL cells decreases, accompanied by an increase in the S phase cell population, while the G2 phase cell population shows no significant change. |
| Animal experiment [2]: | |
Animal models | C57BL6/J mice |
Preparation Method | At 4–6 weeks of age, the mice were inoculated with 1 × 106 RMA cells by subcutaneous injection into the right axilla. Once tumors became palpable, drug interventions were administered. While the control group was given an equivalent volume of solvent, the treatment groups were given an intraperitoneal injection of 15mg/kg of CBL0137. The cisplatin treatment group was given 1mg/kg cisplatin via intraperitoneal injection (total volume: 0.15mL), with the corresponding control group receiving an equivalent solvent injection. Anti-mouse PD-1 and its isotype control antibody were administered via intraperitoneal injection at 10mg/kg. Tumor volume and body weight were monitored using calipers and an electronic balance. The experiment was terminated when the tumor volume in mice approached 2000mm3. Euthanasia was performed using cervical dislocation, and the final tumor volume and weight were recorded. |
Dosage form | 15mg/kg/day for 6 days; i.p. |
Applications | CBL0137 treatment significantly inhibited the tumor growth in RMA tumor-bearing mice, and the combined use with anti-PD-1 was more effective than treatment alone. |
References: | |
| Cas No. | 1197397-89-9 | SDF | |
| 别名 | CBL0137盐酸盐,CBLC137,Curaxin 137 | ||
| 化学名 | 1,1'-[9-[2-[(1-methylethyl)imino]ethyl]-9H-carbazole-3,6-diyl]bis-ethanone, monohydrochloride | ||
| Canonical SMILES | CC(C1=CC=C2C(C(C=C(C(C)=O)C=C3)=C3N2CCNC(C)C)=C1)=O.Cl | ||
| 分子式 | C21H24N2O2 • HCl | 分子量 | 372.9 |
| 溶解度 | ≤25mg/ml in DMSO;20mg/ml in dimethyl formamide | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6817 mL | 13.4084 mL | 26.8168 mL |
| 5 mM | 536.3 μL | 2.6817 mL | 5.3634 mL |
| 10 mM | 268.2 μL | 1.3408 mL | 2.6817 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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