ACY-738是一种具有口服活性的选择性组蛋白去乙酰化酶6（HDAC6；IC50=1.7nM）抑制剂。
Cas No.:1375465-91-0
Sample solution is provided at 25 µL, 10mM.
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ACY-738 is an orally active and selective inhibitor of histone deacetylase 6 (HDAC6; IC50=1.7nM). ACY-738 also inhibits the activity of HDAC1 (IC50=94nM), HDAC2 (IC50=128nM), and HDAC3 (IC50=218nM)[1-2]. ACY-738 can be used in research related to neurodegenerative diseases, tumors, inflammation, and autoimmune diseases[3-4].
In vitro, treatment of human multiple myeloma cell lines (such as U266, NCI-H929, etc.) and primary multiple myeloma cells with ACY-738 (5μM or 10μM) for 48 hours significantly induced tumor cell death[5]. Treatment of patient-derived L0, S3, S7 human glioma cells and murine KR158 glioma cells with ACY-738 (0.5–5μM) for 24 hours to 5 days. ACY-738 significantly inhibited tumor cell proliferation[6].
In vivo, intraperitoneal administration of ACY-738 (20mg/kg) to experimental autoimmune encephalomyelitis (EAE) mice on days 9 and 10 post-immunization significantly delayed disease onset, reduced disease severity, and improved short-term memory[7]. Intraperitoneal administration of ACY-738 (5mg/kg or 20mg/kg) to NZB/W F1 mice five days a week for 16 weeks. ACY-738 significantly alleviated the severity of proteinuria and improved mouse survival. ACY-738 increased the proportion of splenic regulatory T cells and reduced the deposition of IgG and C3 immune complexes in the kidneys, as well as SLE-related renal pathological damage[8].
References:
[1] Jochems J, Boulden J, Lee BG, et al. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400.
[2] Ren J, Liao X, Vieson MD, et al. Selective HDAC6 inhibition decreases early stage of lupus nephritis by down-regulating both innate and adaptive immune responses. Clin Exp Immunol. 2018 Jan;191(1):19-31.
[3] Majid T, Griffin D, Criss Z 2nd, et al. Pharmocologic treatment with histone deacetylase 6 inhibitor (ACY-738) recovers Alzheimer's disease phenotype in amyloid precursor protein/presenilin 1 (APP/PS1) mice. Alzheimers Dement (N Y). 2015 Oct 11;1(3):170-181.
[4] Xu D, Luo XM, Reilly CM. HDAC6 Deletion Decreases Pristane-induced Inflammation. Immunohorizons. 2024 Sep 1;8(9):668-678.
[5] Mithraprabhu S, Khong T, Jones SS, et al. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013 Aug;162(4):559-62.
[6] Shi P, Hoang-Minh LB, Tian J, et al. HDAC6 Signaling at Primary Cilia Promotes Proliferation and Restricts Differentiation of Glioma Cells. Cancers (Basel). 2021 Apr 1;13(7):1644.
[7] Regna NL, Vieson MD, Luo XM, et al. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73.
[8] LoPresti P. The Selective HDAC6 Inhibitor ACY-738 Impacts Memory and Disease Regulation in an Animal Model of Multiple Sclerosis. Front Neurol. 2019 Jun 28;10:519.
ACY-738是一种具有口服活性的选择性组蛋白去乙酰化酶6（HDAC6；IC50=1.7nM）抑制剂。ACY-738 还可以抑制HDAC1（IC50=94nM），HDAC2（IC50=128nM）和HDAC3（IC50=218nM）的活性[1-2]。ACY-738可用于神经退行性疾病、肿瘤、炎症与自身免疫疾病的相关研究[3-4]。
在体外，ACY-738（5μM或10μM）处理人多发性骨髓瘤细胞系（如U266、NCI-H929等）及原代多发性骨髓瘤细胞48小时，显著诱导肿瘤细胞死亡[5]。ACY-738（0.5–5μM）处理患者来源的L0、S3、S7人胶质瘤细胞及小鼠KR158胶质瘤细胞24小时至5天。ACY-738显著抑制肿瘤细胞增殖[6]。
在体内，ACY-738（20mg/kg）在免疫后第9天和第10天对实验性自身免疫性脑脊髓炎（EAE）小鼠进行腹腔注射处理，显著延缓了疾病发作并减轻了疾病严重程度，同时改善了短期记忆[7]。ACY-738（5mg/kg或20mg/kg）每周5天腹腔注射于NZB/W F1小鼠，连续16周。ACY-738显著减轻了蛋白尿严重程度，提高了小鼠存活率。ACY-738增加了脾脏调节性T细胞的比例，并降低了肾脏中IgG和C3的免疫复合物沉积及SLE相关的肾脏病理损伤[8]。
| Cell experiment [1]: | |
Cell lines | Patient-derived L0, S3, S7 human glioma cells and murine KR158 glioma cells |
Preparation Method | Patient-derived glioma cells were grown as floating spheres in serum-free neural stem cell media. Murine KR158 glioma cells were grown adherent in DMEM supplemented with 10% fetal bovine serum (FBS). Cells were treated with ACY-738 (0.5–5μM). |
Reaction Conditions | 0.5–5μM; 24 hours to 5 days. |
Applications | ACY-738 significantly inhibited tumor cell proliferation. ACY-738 concurrently reduced the expression of the proliferative marker Ki67 and increased the expression of the differentiation marker TUJ1, thereby inducing cell differentiation. This effect at low concentrations was dependent on the presence of primary cilia on the tumor cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 female mice with Experimental Autoimmune Encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG35-55) emulsion. |
Preparation Method | EAE was induced in mice via subcutaneous immunization. The mice was treated with ACY-738 (20mg/kg). |
Dosage form | 20mg/kg; i.p.; administered on day 9 and day 10 post-immunization. |
Applications | CY-738 treatment delayed disease onset and reduced disease severity in EAE mice. ACY-738 increased short-term memory in the cross-maze test. |
References: | |
| Cas No. | 1375465-91-0 | SDF | |
| 别名 | N-羟基-2-[(1-苯基环丙基)氨基]-5-嘧啶甲酰胺 | ||
| Canonical SMILES | O=C(NO)C(C=N1)=CN=C1NC2(CC2)C3=CC=CC=C3 | ||
| 分子式 | C14H14N4O2 | 分子量 | 270.29 |
| 溶解度 | DMSO : ≥ 32 mg/mL (118.39 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6997 mL | 18.4986 mL | 36.9973 mL |
| 5 mM | 739.9 μL | 3.6997 mL | 7.3995 mL |
| 10 mM | 370 μL | 1.8499 mL | 3.6997 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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