TGN 020 is a selective aquaporin 4 (AQP4) inhibitor with an IC50 value of 3μM[1]. AQP4 is mainly located in the astrocyte end feet around brain blood vessels and regulates ion and water homeostasis in the brain[2]. TGN 020 is an alkyl chain-based protein degradation targeted chimeric molecule (PROTAC) linker that can be used for the synthesis of PROTAC[3].
In vitro, TGN 020 (100nM) treatment of TR-MUL5 cells for 48-72h inhibited the increase in cell volume and the production of intracellular ROS under high glucose conditions[4].
In vivo, TGN 020 (100mg/kg) was intraperitoneally injected into rats with spinal cord compression injury, which reduced spinal cord edema, inhibited glial scar formation, and promoted axon regeneration[5]. TGN 020 (200mg/kg) was intraperitoneally injected into mice with cerebral ischemia-reperfusion injury, which reduced injury-induced inflammation and cell apoptosis, improved lymphatic function, and inhibited the ERK1/2 pathway[6].
References:
[1] Nishikawa Y, Oku H, Morishita S, et al. Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve[J]. Experimental Eye Research, 2016, 146: 118-127.
[2] Rosu G C, Catalin B, Balseanu T A, et al. Inhibition of aquaporin 4 decreases amyloid Aβ40 drainage around cerebral vessels[J]. Molecular neurobiology, 2020, 57: 4720-4734.
[3] Yuan Y, Peng W, Lei J, et al. AQP4 Endocytosis-Lysosome Degradation Mediated by MMP-9/β-DG Involved in Diabetes Cognitive Impairment[J]. Molecular Neurobiology, 2024: 1-16.
[4] Oosuka S, Kida T, Oku H, et al. Effects of an aquaporin 4 inhibitor, TGN-020, on murine diabetic retina[J]. International Journal of Molecular Sciences, 2020, 21(7): 2324.
[5] Li J, Jia Z, Xu W, et al. TGN-020 alleviates edema and inhibits astrocyte activation and glial scar formation after spinal cord compression injury in rats[J]. Life sciences, 2019, 222: 148-157.
[6] Li X, Xie Z, Zhou Q, et al. TGN-020 Alleviate Inflammation and Apoptosis After Cerebral Ischemia–Reperfusion Injury in Mice Through Glymphatic and ERK1/2 Signaling Pathway[J]. Molecular Neurobiology, 2024, 61(2): 1175-1186.
TGN 020是一种选择性水通道蛋白4（AQP4）抑制剂，IC50值为3μM[1]。AQP4主要位于脑血管周围的星形胶质细胞末足，调节大脑中的离子和水稳态[2]。TGN 020是一种基于烷基链的蛋白降解靶向嵌合分子（PROTAC）接头，可用于PROTAC的合成[3]。
在体外，TGN 020（100nM）处理TR-MUL5细胞48-72h，抑制了高糖条件下细胞体积的增加和细胞内ROS的产生[4]。
在体内，TGN 020（100mg/kg）通过腹腔注射治疗脊髓压迫损伤大鼠，减轻了脊髓水肿，抑制了神经胶质瘢痕形成，促进了轴突再生[5]。TGN 020（200mg/kg）通过腹腔注射治疗脑缺血再灌注损伤小鼠，减轻了损伤引起的炎症和细胞凋亡，改善了淋巴功能，抑制了ERK1/2通路[6]。