Tubastatin A is a potent and selective HDAC6 inhibitor with an IC50 value of 15 nM [1]. Tubastatin A is also a novel GPX4 inhibitor that directly binds to GPX4 and induces ferroptosis in breast cancer cells[2].
Tubastatin A protected against HCA induced neuronal cell death in a dose-dependent manner. Tubastatin A induced the hyperacetylation of α-tubulin at 2.5 μM[1]. Tubastatin A (32.5µM, 30µM) can inhibit cell colony formation and migration ability and promote apoptosis[3]. Tubastatin A can effectively upregulate the levels of SOD1 and HO-1 and reduce the oxidative stress of chondrocytes [4]. Tubastatin A at 10 μM also significantly inhibited cell proliferation in cholangiocarcinoma cells[5].
Tubastatin A (50mg/kg/day) treatment effectively reduces the expression of HDAC6 in the cartilage of osteoarthritis mice and improves osteoarthritis in mice with surgically destroyed medial meniscus (DMM)[4]. Tubastatin A treatment reduced tumor growth and induces ciliogenesis in rat orthotopic model of cholangiocarcinoma at 10 mg/kg[5].
References:
[1] Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP: Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 2010, 132(31):10842-10846.
[2] Liu, Shan., Zhang, Hai-Liang., Li, Jing., Ye, Zhi-Peng., Du, Tian. Tubastatin A potently inhibits GPX4 activity to potentiate cancer radiotherapy through boosting ferroptosis. Redox biology, 2023.
[3] Urdiciain A, Erausquin E, Meléndez B, Rey JA, Idoate MA, Castresana JS. Tubastatin A, an inhibitor of HDAC6, enhances temozolomide-induced apoptosis and reverses the malignant phenotype of glioblastoma cells. Int J Oncol. 2019 May;54(5):1797-1808.
[4] Shen Z, Ji K, Cai Z, Huang C, He X, Xu H, Chen G. Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy. Aging (Albany NY). 2021 Mar 19;13(7):9820-9837.
[5] Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, LaRusso NF: HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res 2013, 73(7):2259-2270.
Tubastatin A 是一种有效的选择性 HDAC6 抑制剂，IC50 值为 15 nM [1]。并且Tubastatin A也是一种新型GPX4抑制剂，Tubastatin A 直接与 GPX4 结合，诱导乳腺癌细胞铁死亡[2]。
Tubastatin A以剂量依赖性方式防止 HCA 诱导的神经元细胞死亡，在 2.5 μM 浓度下可以诱导 α-微管蛋白过度乙酰化[1] 。Tubastatin A（32.5µM，30µM）可抑制细胞的集落形成、迁移能力并促进其凋亡[3]。Tubastatin A 能够有效上调SOD1和HO-1的水平，减少软骨细胞的氧化应激[4]。10μM 的 Tubastatin A 还可显着抑制胆管癌细胞的增殖[5]。
Tubastatin A (50mg/kg/day)治疗有效降低骨关节炎小鼠软骨中 HDAC6 的表达，改善被手术破坏内侧半月板（ DMM）小鼠的骨关节炎[4]。在胆管癌大鼠原位模型中，10 mg/kg 的 Tubastatin A 治疗可减少肿瘤生长并诱导纤毛生成[5] 。