FABPs ligand 6 is an FABP5 and FABP7 inhibitor with Kd values of 874nM and 20nM, respectively [1]. The FABPs ligand 6 can stabilize the mitochondrial membrane potential and reduce the release of pro-inflammatory cytokines IL-1β and TNF-α[2]. FABPs ligand 6 has been widely used to reduce cerebral ischemia-reperfusion injury in animals and to improve neurological deficits[3].
In vitro, FABPs ligand 6 treatment (10μM) for 48 hours inhibited the oligomerization/aggregation of α-synuclein in U251 cells and rescued cell death[4]. Treatment with 10μM FABPs ligand 6 for 48 hours significantly reduced the proliferation and migration of Skmel23 cells, and inhibited the activation of the Wnt/β-catenin signaling pathway[5].
In vivo, FABPs ligand 6 treatment via a single oral administration at a dose of 3mg/kg effectively reduced the brain infarction volume and neurological deficits 30minutes after cerebral ischemia-reperfusion in mice[3].
References:
[1] Cheng A, Jia W, Kawahata I, et al. A novel fatty acid-binding protein 5 and 7 inhibitor ameliorates oligodendrocyte injury in multiple sclerosis mouse models[J]. EBioMedicine, 2021, 72.
[2] Wu C, Lin J, Chen Q, et al. Targeting the FABP Axis: Interplay Between Lipid Metabolism, Neuroinflammation, and Neurodegeneration[J]. Cells, 2025, 14(19): 1502.
[3] Guo Q, Kawahata I, Degawa T, et al. Fatty acid-binding proteins aggravate cerebral ischemia-reperfusion injury in mice[J]. Biomedicines, 2021, 9(5): 529.
[4] Cheng A, Wang Y, Shinoda Y, et al. Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress[J]. Acta Pharmacologica Sinica, 2022, 43(3): 552-562.
[5] Umaru B A, Kagawa Y, Shil S K, et al. Ligand Bound Fatty Acid Binding Protein 7 (FABP7) Drives Melanoma Cell Proliferation Via Modulation of Wnt/β-Catenin Signaling: Umaru et al[J]. Pharmaceutical Research, 2021, 38(3): 479-490.
FABPs ligand 6是一种FABP5和FABP7抑制剂，对FABP5和FABP7的Kd值分别为874nM和20nM[1]。FABPs ligand 6能够稳定线粒体膜电位，并减少促炎细胞因子IL-1β和TNF-α的释放[2]。FABPs ligand 6已被广泛用于减轻动物脑缺血再灌注损伤并改善神经功能缺损[3]。
在体外，使用10μM的FABPs ligand 6处理U251细胞48小时，抑制了α-突触核蛋白的寡聚/聚集并挽救了细胞死亡[4]。使用10μM的FABPs ligand 6处理Skmel23细胞48小时，显著降低了细胞的增殖和迁移，并抑制了Wnt/β-连环蛋白信号通路的激活[5]。
在体内，单次口服3mg/kg剂量的FABPs ligand 6，在小鼠脑缺血再灌注后30分钟有效减少了脑梗死体积和神经功能缺损[3]。