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]。