Golgicide A

Golgicide A is a highly specific and reversible cis-Golgi ADP-ribosylation factor guanine nucleotide exchange factor (ArfGEF GBF1) inhibitor. By selectively targeting GBF1 and reducing the activation of Arf1, Golgicide A blocks intracellular vesicle transport and protein secretion^[1-2]. Golgicide A is utilized in research on infection mechanisms of pathogens such as hepatitis C virus and enteroviruses, as well as in studies on cancer development and progression^[3-4].

In vitro, Golgicide A, at a concentration of 400nM, was used to treat swine testicular (ST) cells infected with Classical Swine Fever Virus (CSFV). Golgicide A significantly inhibited the proliferation of CSFV, reduced the CSFV RNA load in the cells, and suppressed viral particle production^[5]. In Hep3B, HepG2, and MPC5 cells treated with 10µM Golgicide A for 60 minutes, followed by stimulation with EGF (1µg/mL) for 3 minutes, Golgicide A significantly reduced the size of growth factor-induced circular dorsal ruffles^[6].

In vivo, subcutaneous injection of Golgicide A (10mg/kg/day) in hSCARB2 transgenic mice infected with EV-A71 (starting from the onset of infection and administered continuously for 5 days) significantly reduced mouse mortality and alleviated brain tissue pathological damage caused by the viral infection^[7]. In A549-derived lung cancer stem cell tumor-bearing BALB/c nude mice, subcutaneous injection of Golgicide A (20mg/kg/week and 50mg/kg/week) (starting from day 7 post-inoculation, administered weekly for 4 weeks), Golgicide A significantly inhibited tumor growth and induced pyroptosis in lung cancer stem cells^[8].

References:
[1] Sáenz JB, Sun WJ, Chang JW, et al. Golgicide A reveals essential roles for GBF1 in Golgi assembly and function. Nat Chem Biol. 2009 Mar;5(3):157-65.
[2] Farhat R, Ankavay M, Lebsir N, et al. Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication. Cell Microbiol. 2018 Jan;20(1):e12804.
[3] Shen SM, Ji Y, Zhang C, et al. Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role. Nat Commun. 2018 Jun 19;9(1):2392.
[4] van der Linden L, van der Schaar HM, Lanke KH, et al. Differential effects of the putative GBF1 inhibitors Golgicide A and AG1478 on enterovirus replication. J Virol. 2010 Aug;84(15):7535-42.
[5] Liang W, Zheng M, Bao C, et al. CSFV proliferation is associated with GBF1 and Rab2. J Biosci. 2017 Mar;42(1):43-56.
[6] Sun X, Li Y, He Y, et al. Aberrant expression of GTPase-activating protein ARAP1 triggers circular dorsal ruffles associated with malignancy in hepatocellular carcinoma Hep3B cells. Cell Commun Signal. 2025 Feb 11;23(1):75.
[7] He Z, Xia B, Zhao T, et al. Clathrin-Independent Carriers/Glycosylphosphatidylinositol-Anchored-Protein-Enriched Endosomal Compartment Endocytic Pathway Is Critical for Enterovirus A71 Entry Into Human Oral Epidermoid Carcinoma KB Cells. J Med Virol. 2025 May;97(5):e70369.
[8] Zhang F, Zhang SH, Liu T, et al. Golgicide A induces pyroptosis of lung cancer stem cells by regulating dTGN formation via GOLPH3/MYO18A complex. Stem Cell Res Ther. 2025 Mar 7;16(1):121.

Golgicide A是一种高度特异且可逆的顺式高尔基体ADP-核糖基化因子鸟嘌呤核苷酸交换因子（ArfGEF GBF1）抑制剂，Golgicide A通过选择性靶向GBF1并减少Arf1的活化，从而阻断细胞内的囊泡运输和蛋白质分泌^[1-2]。Golgicide A被用于丙型肝炎病毒及肠道病毒等病原体的感染机制和癌症发生发展的研究^[3-4]。

在体外，Golgicide A以400nM浓度处理感染经典猪瘟病毒（CSFV）的猪睾丸（ST）细胞，Golgicide A显著抑制CSFV的增殖，显著降低细胞中CSFV RNA载量，抑制病毒颗粒生成^[5]。Golgicide A（10μM）处理Hep3B、HepG2和MPC5细胞60分钟，随后使用EGF（1μg/mL）处理3分钟，Golgicide A显著减小生长因子诱导的环状背皱褶的尺寸^[6]。

在体内，Golgicide A（10mg/kg/day）皮下注射处理感染EV-A71的hSCARB2转基因小鼠（从感染后开始，连续给药5天），Golgicide A显著降低小鼠死亡率，并减轻病毒感染引起的脑组织病理损伤^[7]。Golgicide A（20mg/kg/周和50mg/kg/周）通过皮下注射处理荷瘤（A549来源肺癌干细胞）BALB/c裸鼠（从接种后第7天开始，每周给药，持续4周），Golgicide A显著抑制肿瘤生长，并诱导肺癌干细胞发生的焦亡^[8]。