PFK-158 is a potent and selective PFKFB3 inhibitor, which shows extensive anti-tumor activity by reducing the uptake of glucose in cancer cells, the production of ATP, the release of lactic acid and inducing apoptosis and autophagy[1].
PFK-158 suppressed cell viability in a dose- and time-dependent manner in EC cells. Co-treatment with PFK158 (5 μM) and CBPt led to a significant increase in the percentage of apoptotic cells in HEC-1B and ARK-2. Furthermore, Western blot analysis revealed that the active form of PARP was significantly increased upon co-treatment, compared to single treatment alone, further demonstrating that the combination treatment enhances cell apoptosis[2]
The efficacy of PFK158 alone and in combination with carboplatin (CBPt) was evaluated on primary tumor growth and metastasis in HeyA8MDR‐bearing nude mice i.p. A marked reduction of tumor growth was observed in the combination treatment.PFK-158 with CBPt significantly reduced ascites and reduced LDs in tumor tissue as seen by immunofluorescence and transmission electron microscopy compared to untreated mice[3]
References:
[1]. Gustafsson NMS, F?rneg?rdh K, et al. Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination. Nat Commun. 2018 Sep 24;9(1):3872.
[2]. Xiao Y, Jin L, et al. Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer. Oncogene. 2021 Feb;40(8):1409-1424.
[3]. Mondal S, Roy D, et al. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int J Cancer. 2019 Jan 1;144(1):178-189.
PFK-158 是一种有效的选择性 PFKFB3 抑制剂，通过减少癌细胞中葡萄糖的摄取、ATP 的产生、乳酸的释放以及诱导细胞凋亡和自噬，显示出广泛的抗肿瘤活性[ 1].
PFK-158 在 EC 细胞中以剂量和时间依赖性方式抑制细胞活力。与 PFK158 (5 μM) 和 CBPt 共同处理导致 HEC-1B 和 ARK-2 中凋亡细胞的百分比显着增加。此外，蛋白质印迹分析显示，与单独的单一治疗相比，联合治疗后 PARP 的活性形式显着增加，进一步证明联合治疗可增强细胞凋亡[2]
PFK158 单独使用和与卡铂 (CBPt) 联合使用对 HeyA8MDR 荷瘤裸鼠 i.p. 原发性肿瘤生长和转移的疗效进行了评估。在联合治疗中观察到肿瘤生长显着减少。与未治疗的小鼠相比，PFK-158 与 CBPt 显着减少腹水并减少肿瘤组织中的 LDs[3] /p>