10058-F4 is a c-Myc inhibitor that inhibits c-Myc-Max dimerization and prevents transcriptional activation of c-Myc target gene expression[1]. 10058-F4 can promote caspase-3-dependent apoptosis and regulate autophagy[2]. 10058-F4 has anti-leukemia effects[3].
In vitro, 10058-F4 (0-200µM) treatment of ovarian cancer cell lines (SKOV3 and Hey cells) for 72h inhibited the proliferation of both cell lines in a dose-dependent manner, with IC50 values of 4.4µM and 3.2µML for SKOV3 and Hey cells, respectively, induced cell cycle arrest and apoptosis, and reduced reactive oxygen species (ROS) and ATP generation[4]. 10058-F4 (60μM) treatment of NALM6 and CEM cells for 24h significantly enhanced dexamethasone (DXM)-induced cell growth inhibition, G0/G1 phase arrest and apoptosis[5]. 10058-F4 (0-150μM) treatment of leukemia cells (HL-60, U937 and NB4 cells) for 72h inhibited the proliferation of all three cell types in a dose-dependent manner, induced cell cycle arrest and apoptosis, and myeloid differentiation[6].
In vivo, 10058-F4 (25mg/kg/day) was administered intraperitoneally to mice with acute colitis, which weakened the LiCl-induced colon regeneration effect and reduced the expression of Ccnd2 and Cad[7]. 10058-F4 (15mg/kg) was administered intraperitoneally to mice with PANC-1 cell xenografts for 30 days, 10058-F4 alone had no significant effect on tumorigenesis, but when used in combination with gemcitabine, it significantly attenuated tumorigenesis and reduced PCNA-positive cells and TUNEL-positive cells[8].
References:
[1] Lin C P, Liu J D, Chow J M, et al. Small-molecule c-Myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells[J]. Anti-cancer drugs, 2007, 18(2): 161-170.
[2] Sheikh‐Zeineddini N, Bashash D, Safaroghli‐Azar A, et al. Suppression of c‐Myc using 10058‐F4 exerts caspase‐3‐dependent apoptosis and intensifies the antileukemic effect of vincristine in pre‐B acute lymphoblastic leukemia cells[J]. Journal of cellular biochemistry, 2019, 120(8): 14004-14016.
[3] Zehtabcheh S, Sheikh‐Zeineddini N, Yousefi A M, et al. Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells[J]. Asian Pacific Journal of Cancer Prevention, 2024, 25(6): 1959-1967.
[4] Wang J, Ma X, Jones H M, et al. Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells[J]. Journal of translational medicine, 2014, 12: 1-11.
[5] Lv M, Wang Y, Wu W, et al. C Myc inhibitor 10058 F4 increases the efficacy of dexamethasone on acute lymphoblastic leukaemia cells[J]. Molecular Medicine Reports, 2018, 18(1): 421-428.
[6] Huang M J, Cheng Y, Liu C R, et al. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia[J]. Experimental hematology, 2006, 34(11): 1480-1489.
[7] Raup-Konsavage W M, Cooper T K, Yochum G S. A role for MYC in lithium-stimulated repair of the colonic epithelium after DSS-induced damage in mice[J]. Digestive diseases and sciences, 2016, 61: 410-422.
[8] Zhang M, Fan H Y, Li S C. Inhibition of c-Myc by 10058-F4 induces growth arrest and chemosensitivity in pancreatic ductal adenocarcinoma[J]. Biomedicine & pharmacotherapy, 2015, 73: 123-128.
10058-F4是一种c-Myc抑制剂，抑制c-Myc-Max二聚化，阻止c-Myc靶基因表达的转录激活[1]。10058-F4可促进caspase-3依赖的细胞凋亡并调节自噬[2]。10058-F4具有抗白血病作用[3]。
在体外，10058-F4（0-200µM）处理卵巢癌细胞系（SKOV3和Hey细胞）72h，均以剂量依赖性方式抑制了两种细胞增殖，对SKOV3和Hey细胞的IC50值分别为4.4µM和3.2µML，诱导了细胞周期停滞和凋亡，减少了活性氧（ROS）和ATP生成[4]。10058-F4（60μM）处理NALM6和CEM细胞24h，显著增强了地塞米松（DXM）诱导的细胞生长抑制、G0/G1期停滞和凋亡[5]。10058-F4（0-150μM）处理白血病细胞（HL-60、U937和NB4细胞）72h，均以剂量依赖性方式抑制了三种细胞增殖，诱导了细胞周期停滞和凋亡以及骨髓分化[6]。
在体内，10058-F4（25mg/kg/day）通过腹腔注射急性结肠炎治疗小鼠，削弱了LiCl诱导的促进结肠再生作用，降低了Ccnd2和Cad的表达[7]。10058-F4（15mg/kg）通过腹腔注射治疗PANC-1细胞异种移植小鼠30天，10058-F4单独治疗对肿瘤发生没有显著影响，与吉西他滨联合使用时显著减弱了肿瘤发生，减少了PCNA阳性细胞和TUNEL阳性细胞[8]。