ITSA-1 (ITSA1), a histone deacetylase (HDAC) activator, can prevent arterial laminar shear stress-induced endothelial cell detachment and reduce VCAM-1 expression in vascular endothelial cells (vECs)[1].
In vitro, ITSA-1 (150μM; 0, 3, 6; 24h) can reverse the inflammatory response in vascular endothelial cells (vECs) induced by amyotrophic lateral sclerosis (ALS) by increasing the expression of histone deacetylases (HDACs) and histone H3 lysine 9 trimethylation (H3K9me3)[2]. Short-term stimulation with ITSA-1 (0, 50, 100, 200 and 400ng/ml; 0, 24 and 48h) induces epithelial-mesenchymal transition in nasopharyngeal carcinoma cells[3].
In vivo, ITSA-1 (0.5mg/kg; i.p.) enhances the recovery and survival of post-ROSC rats by diminishing histone acetylation and mitigating systemic inflammation[1]. A blockade of HDAC3 inhibition in CBS+/− mice by HDAC activator ITSA-1 (0.5mg/kg/3 times/week; 8 weeks; i.p.), led to the remodeling of histone landscapes in the genome and thereby attenuated histone acetylation-dependent inflammatory signaling[4].
References:
[1] Zhang C, Wei H, Zhang Q, et al. The Histone Deacetylase Activator ITSA-1 Improves the Prognosis of Cardiac Arrest Rats by Alleviating Systemic Inflammatory Responses Following Cardiopulmonary Resuscitation. Mediators Inflamm. 2025 Mar 20;2025:8156593.
[2] Wang TY, Chang MM, Li YJ, et al. Maintenance of HDACs and H3K9me3 Prevents Arterial Flow-Induced Venous Endothelial Damage. Front Cell Dev Biol. 2021 Apr 9;9:642150.
[3] Shen Z, Liao X, Shao Z, et al. Short-term stimulation with histone deacetylase inhibitor trichostatin a induces epithelial-mesenchymal transition in nasopharyngeal carcinoma cells without increasing cell invasion ability. BMC Cancer. 2019 Mar 22;19(1):262.
[4] Behera J, Kelly KE, Voor MJ, et al. Hydrogen Sulfide Promotes Bone Homeostasis by Balancing Inflammatory Cytokine Signaling in CBS-Deficient Mice through an Epigenetic Mechanism. Sci Rep. 2018 Oct 15;8(1):15226.
ITSA-1 (ITSA1)是一种组蛋白去乙酰化酶（HDAC）激活剂，可以防止动脉层流剪切力诱导的内皮细胞脱落，并降低血管内皮细胞（vECs）中VCAM-1的表达[1]。
体外实验中，ITSA-1（150µM; 0, 3, 6和24小时）可以通过增加组蛋白去乙酰化酶（HDACs）和组蛋白H3第9位赖氨酸三甲基化（H3K9me3）的表达，逆转由肌萎缩侧索硬化症（ALS）诱导的血管内皮细胞（vECs）的炎症反应[2]。短期刺激ITSA-1（0, 50, 100, 200和400ng/ml; 0, 24和48小时）可以诱导鼻咽癌细胞发生上皮-间充质转化[3]。
体内实验中，ITSA-1（0.5mg/kg; 腹腔注射）通过减少组蛋白乙酰化和减轻全身炎症反应，增强了心脏骤停后复苏（post-ROSC）大鼠的恢复和存活率[1]。通过组蛋白去乙酰化酶激活剂ITSA-1（0.5mg/kg/每周3次; 8周; 腹腔注射）阻断CBS+/−小鼠中HDAC3的抑制，导致基因组中组蛋白景观的重塑，从而减轻了依赖组蛋白乙酰化的炎症信号传导[4]。