SBFI-26 is a selective and competitive inhibitor of fatty acid binding proteins FABP5 and FABP7, SBFI-26 binds to the canonical ligand-binding pocket of FABP5[2],with Kjs of 0.9 μM and 0.4 μM for FABP5 and ABP7, respectively. SBFI-26 produces anti-nociceptive and anti-inflammatory effects[1,2].
The FABP inhibitor SBFI-26 does not decrease the amplitude of EPSCs and is a weak agonist of PPARα and PPARγ receptors. Confirming its selectivity for FABPs, SBFI-26failed to reduce AEA uptake in cells bearing a knockdown of FABP5, the main FABP expressed in HeLa cells. Additionally, SBFI-26 does not inhibit FAAH. Collectively, SBFI-26 is a selective FABP inhibitor[1].
SBFI-26 produces analgesic and anti-inflammatory effects in mice, SBFI-26 (20 mg/kg) significantly reduced carrageenan-induced thermal hyperalgesia and paw edema[1]. FABP5 was the only one dramatically upregulated along with increased protein expression in the established PH-LHD mouse model. Inhibition of FABP5 by SBFI-26 injection abrogated pulmonary artery remodelling in PH-LHD and improved cardiac function[3].
References:
[1]: Berger WT, Ralph BP, et,al. Targeting fatty acid binding protein (FABP) anandamide transporters - a novel strategy for development of anti-inflammatory and anti-nociceptive drugs. PLoS One. 2012;7(12):e50968. doi: 10.1371/journal.pone.0050968. Epub 2012 Dec 7. PMID: 23236415; PMCID: PMC3517626.
[2]: Hsu HC, Tong S, et,al. The Antinociceptive Agent SBFI-26 Binds to Anandamide Transporters FABP5 and FABP7 at Two Different Sites. Biochemistry. 2017 Jul 11;56(27):3454-3462. doi: 10.1021/acs.biochem.7b00194. Epub 2017 Jun 28. PMID: 28632393; PMCID: PMC5884075.
[3]: Lei Q, Yu Z, et,al. Fatty acid-binding protein 5 aggravates pulmonary artery fibrosis in pulmonary hypertension secondary to left heart disease via activating wnt/β-catenin pathway. J Adv Res. 2022 Sep;40:197-206. doi: 10.1016/j.jare.2021.11.011. Epub 2021 Nov 26. PMID: 36100327; PMCID: PMC9481948.
SBFI-26 是脂肪酸结合蛋白 FABP5 和 FABP7 的选择性和竞争性抑制剂，SBFI-26 与 FABP5[2] 的典型配体结合口袋结合，Kjs 为 0.9 μM FABP5 和 ABP7 分别为 0.4 μM。 SBFI-26 具有抗伤害和抗炎作用[1,2]。
FABP 抑制剂 SBFI-26 不会降低 EPSC 的振幅，并且是 PPARα 和 PPARγ 受体的弱激动剂。证实其对 FABP 的选择性，SBFI-26 未能减少具有 FABP5 敲低的细胞中的 AEA 摄取，FABP5 是 HeLa 细胞中表达的主要 FABP。此外，SBFI-26 不抑制 FAAH。总的来说，SBFI-26 是一种选择性 FABP 抑制剂[1]。
SBFI-26 在小鼠体内产生镇痛和抗炎作用，SBFI-26 (20 mg/kg) 显着减轻角叉菜胶诱导的热痛觉过敏和爪水肿[1]。在已建立的 PH-LHD 小鼠模型中，FABP5 是唯一一种随着蛋白质表达的增加而显着上调的基因。 SBFI-26 注射液抑制 FABP5 可消除 PH-LHD 肺动脉重构并改善心功能[3]。