Endosidin 2 is a selective inhibitor targeting the conserved exosome subunit EXO70[1]. Endosidin 2 binds to the C-terminal domain of EXO70, blocking its protein-protein interactions with other components of the outer capsule complex, thereby inhibiting exosomes and systemic circulation[2]. Endosidin 2 is commonly used in the study of endocytosis and recirculation mechanisms in plant and mammalian cells[3][4].
In vitro, treatment of peripheral blood mononuclear cells (PBMCs) with Endosidin 2 (40μM; 1-2h) significantly inhibited the translocation of ACE2 to the cell surface induced by R848 and LPS[5]. Treatment of skeletal myoblast cells with Endosidin 2(100μM; 30min) leads to impaired GLUT4 trafficking to the plasma membrane and hinders glucose uptake in response to an insulin stimulus[6].
In vivo, in the intraperitoneal transplantation model of ovarian cancer A2780CR cells, Endosidin 2 (6mg/kg every 6 days for 24 days; i.p.) significantly enhances the sensitivity of cisplatin in ovarian cancer cells by inhibiting the function of the Exo70 subunit of the outer capsule complex, overcomes cisplatin resistance in ovarian cancer cells, and thereby reduces tumor growth and metastasis[7].
References:
[1] Zhang C, Brown MQ, van de Ven W, et al. Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis. Proc Natl Acad Sci U S A. 2016;113(1):E41-E50.
[2] Huang L, Li X, Li Y, et al. Endosidin2-14 Targets the Exocyst Complex in Plants and Fungal Pathogens to Inhibit Exocytosis. Plant Physiol. 2019;180(3):1756-1770.
[3] Huang L, Zhang C. Use Endosidin2 to Study Plant Exocytosis and Vacuolar Trafficking. Methods Mol Biol. 2018;1789:167-175.
[4] Ciampelli C, Galleri G, Puggioni S, et al. Inhibition of the Exocyst Complex Attenuates the LRRK2 Pathological Effects. Int J Mol Sci. 2023;24(16):12656.
[5] Yao Y, Subedi K, Liu T, et al. Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes. Cell Discov. 2022;8(1):89.
[6] Fujimoto BA, Young M, Carter L, et al. The exocyst complex regulates insulin-stimulated glucose uptake of skeletal muscle cells. Am J Physiol Endocrinol Metab. 2019;317(6):E957-E972.
[7] Zhao Y, Hong X, Chen X, et al. Deregulation of Exo70 Facilitates Innate and Acquired Cisplatin Resistance in Epithelial Ovarian Cancer by Promoting Cisplatin Efflux. Cancers (Basel). 2021;13(14):3467.
Endosidin 2是一种选择性抑制剂，靶向保守的外囊复合体亚基EXO70[1]。Endosidin 2结合EXO70的C端结构域，阻断其与其他外囊复合体组分的蛋白-蛋白相互作用，从而抑制外泌作用及内体循环[2]。Endosidin 2常用于植物及哺乳动物细胞内吞 - 再循环机制研究[3][4]。
在体外研究中，用Endosidin 2（40μM；1 - 2 小时）处理外周血单核细胞（PBMCs）显著抑制了由R848和LPS诱导的ACE2向细胞表面的转位[5]。在骨骼肌母细胞中，Endosidin 2（100μM；30分钟）处理导致胰岛素刺激下GLUT4向质膜的运输受损，进而阻碍了葡萄糖的摄取[6]。
在体内研究中，在卵巢癌A2780CR细胞腹腔移植肿瘤模型中，Endosidin 2（每6天6mg/kg; 24天；腹腔注射）通过抑制外囊复合体亚基Exo70的功能显著增强了顺铂在卵巢癌细胞中的敏感性，克服了卵巢癌细胞的顺铂耐药性，从而减少了肿瘤的生长和转移[7]。