Tucidinostat

Tucidinostat, also known as Chidamide or CS055/HBI-8000, is an inhibitor of HDAC1, HDAC2, HDAC3, and HDAC10, with IC₅₀ values of 95 nM, 160 nM, 67 nM, and 78 nM, respectively. It belongs to the benzamide class of selective HDAC inhibitors and is capable of promoting histone H3 acetylation. Tucidinostat has demonstrated efficacy in inhibiting tumor growth across a range of malignant tumors^[1-2].

Tucidinostat(0.25-8uM; 24-96h) inhibited the proliferation of K562 cells in a dose- and time-dependent manner. It achieved this by blocking cells in the G0/G1 phase through downregulation of cyclin-dependent kinase 4 (CDK4). Additionally, Tucidinostat induced apoptosis by upregulating Bax and downregulating Bcl-2^[3]. Tucidinostat(0.1-6uM ;72 h) elicited growth inhibition and cell cycle arrest in rituximab-resistant B-cell lymphoma cell lines (RRCL) ^[4]. Tucidinostat(0, 2.5, and 10 μM; 48 h) significantly upregulated E-cadherin expression in TGF-β-treated cells and suppressed the migration of lung cancer cells^[5].

Tucidinostat(25 mg/kg; p.o; thrice weekly for 2 weeks) inhibited the formation of subcutaneous leukemia tumors. Following treatment with Tucidinostat, the tumor size was significantly reduced^[6]. Tucidinostat, at a dosage of 5 mg/kg, combined with fluzoparib, more significantly inhibited neoplasm growth compared to monotherapy^[7].

[1]. Ning ZQ, Li ZB, et al. Chidamide (CS055/HBI-8000): a new histone deacetylase inhibitor of the benzamide class with antitumor activity and the ability to enhance immune cell-mediated tumor cell cytotoxicity. Cancer Chemother Pharm. 2012;69:901–9.
[2]. Liu L, Chen B, et al. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells. Biochem Biophys Res Commun. 2010 Feb 5;392(2):190-5. doi: 10.1016/j.bbrc.2010.01.011. Epub 2010 Jan 7. PMID: 20060381.
[3]. Liang S, Zhou X, et al. Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation. Curr Pharm Des. 2021;27(26):2990-2998. doi: 10.2174/1381612827666210701152250. PMID: 34218775.
[4]. Xue K, Wu JC, et al. Chidamide triggers BTG1-mediated autophagy and reverses the chemotherapy resistance in the relapsed/refractory B-cell lymphoma. Cell Death Dis. 2021 Oct 1;12(10):900. doi: 10.1038/s41419-021-04187-5. PMID: 34599153; PMCID: PMC8486747.
[5]. Lin SH, Wang BY, et al. Chidamide alleviates TGF-β-induced epithelial-mesenchymal transition in lung cancer cell lines. Mol Biol Rep. 2016 Jul;43(7):687-95. doi: 10.1007/s11033-016-4005-z. Epub 2016 May 17. PMID: 27188428.
[6]. Xue K, Wu JC, et al. Chidamide triggers BTG1-mediated autophagy and reverses the chemotherapy resistance in the relapsed/refractory B-cell lymphoma. Cell Death Dis. 2021 Oct 1;12(10):900. doi: 10.1038/s41419-021-04187-5. PMID: 34599153; PMCID: PMC8486747.
[7]. Li X, Yuan X, et al. Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells. Front Oncol. 2022 Feb 18;12:819714. doi: 10.3389/fonc.2022.819714. PMID: 35251986; PMCID: PMC8894594.

Tucidinostat，也称为Chidamide或CS055/HBI-8000，是HDAC1、HDAC2、HDAC3和HDAC10的抑制剂，IC₅₀值分别为95 nM、160 nM、67 nM和78 nM。它属于苯甲酰胺类选择性HDAC抑制剂，能够促进组蛋白H3乙酰化。Tucidinostat已被证明对多种恶性肿瘤具有抑制肿瘤生长的功效^[1-2]。

Tucidinostat(0.25-8uM; 24-96h) 对K562细胞的增殖具有剂量依赖性和时间依赖性。它下调细胞周期蛋白依赖性激酶4 (CDK4)阻断G0/G1期的细胞。此外，Tucidinostat通过上调Bax和下调Bcl-2诱导细胞凋亡^[3]。在利妥昔单抗耐药b细胞淋巴瘤细胞系(RRCL)中，Tucidinostat(0.1-6uM;72 h)可引起生长抑制和细胞周期阻滞^[4]。Tucidinostat(0、2.5、10 μM);48 h)显著上调TGF-β处理细胞中E-cadherin的表达，抑制肺癌细胞的迁移^[5]。

Tucidinostat(25 mg/kg; p.o; thrice weekly for 2 weeks)抑制皮下白血病肿瘤的形成，应用Tucidinostat治疗后，肿瘤大小明显减小^[6]。与单药治疗相比，5 mg/kg剂量的途西替他与氟唑帕尼联用能更显著地抑制肿瘤生长^[7]。