hHDAC3 (IC50 = 157 nM); hHDAC1 (IC50 = 198 nM); hHDAC11 (IC50 = 292 nM); hHDAC6 (IC50 = 315 nM); hHDAC2 (IC50 = 325 nM); hHDAC10 (IC50 = 340 nM); hHDAC7 (IC50 = 524 nM); hHDAC5 (IC50 = 532 nM); hHDAC9 (IC50 = 541 nM); hHDAC8 (IC50 = 854 nM); hHDAC4 (IC50 = 1059 nM); HD1-B (IC50 = 7.5 nM); HD1-A (IC50 = 16 nM); HD2 (IC50 = 10 nM)

体外活性：在 LPS 刺激的培养人外周血单核细胞 (PBMC) 中，ITF2357 减少 TNFα、IL-1α、IL-1β 和 IFNγ 的释放，IC50 分别为 10-25 nM。使用 IL-12 与 IL-18 的组合，ITF2357 减少 IFNγ 和 IL-6 的产生，IC50 为 12.5-25 nM，与 IL-1 或 TNFα 的减少无关。 ITF2357 在多发性骨髓瘤 (MM) 细胞系（RPMI8226、NCI-H929、JJN3、KMS 11、KMS 12、KMS 18 和 KMS 20）和急性髓性白血病 (AML) 细胞系（HL-60、THP-1）中具有细胞毒性、U937、KASUMI、KG-1 和 TF-1），IC50 为 200 nM。 ITF2357 激活内在的细胞凋亡途径，上调 p21 并下调 Bcl-2 和 Mcl-1。 ITF2357 可抑制间充质基质细胞 (MSC) 中 IL-6、VEGF 和 IFNγ 的产生 80-95%。 ITF2357 有利于炎症条件下 β 细胞的存活。浓度为 25 和 250 nM 的 ITF2357 可增加胰岛细胞活力，增强胰岛素分泌，抑制 MIP-1α 和 MIP-2 的释放，减少 NO 产生并降低细胞凋亡率。激酶测定：加入 100 μL 底物（2×105 cpm）、40 μL 缓冲液（50 mM Tris-HCl，pH 8.0，750 mM NaCl，5 mM PMSF，50% 甘油）和 95 μL 蒸馏水进行测定。粗细胞提取物（5 μL）。添加 ITF2357 (50 μL) 以测试 HDAC 抑制。将混合物在室温下孵育过夜，并通过添加 50 μL 1 mL 蒸馏水中含有 259 μL 37% HCl 和 28 μL 乙酸的溶液来淬灭反应。从底物中释放的[3H]乙酰基残基通过用600μL乙酸乙酯进行有机萃取来分离，将200μL有机相添加到标准闪烁液中，并通过β计数器测量放射性。 HDAC 的抑制表示为抑制 50% 对照活性的浓度（通过将含有抑制剂的样品的放射性与仅含有细胞粗提取物的对照的放射性进行比较）。细胞测定：洗涤后，将分离的PBMC以5×106/mL重悬于含有5%FCS的RPMI中，加入到50mL锥形聚丙烯管中，并在4℃下放置过夜。第二天早上将 PBMC 重悬并添加到 96 孔平板微量滴定板中（每孔 100 μL）。然后添加 ITF2357 进行抑制研究，并将板在 37°C 下孵育 1 小时，然后用 LPS 或其他刺激剂以每孔终体积 200 μL 刺激细胞。 37℃孵育24小时后除去上清液，并冷冻在-80℃直至测定细胞因子。

ITF2357 (1-10 mg/kg) 可使小鼠 LPS 诱导的血清 TNFα 和 IFNγ 降低 50% 以上。小鼠循环中的 PBMC 中的 ITF2357 不会抑制抗 CD3 诱导的细胞因子。在刀豆蛋白 A 诱导的肝炎中，ITF2357（1 或 5 mg/kg）可显着减轻肝损伤。 ITF2357 (10 mg/kg) 显着延长接种 AML-PS 体内传代细胞系的严重联合免疫缺陷小鼠的存活时间。在闭合性头部损伤 (CHI) 小鼠模型中，ITF2357 (10 mg/kg) 可改善神经行为恢复、减少神经元变性、缩小病变体积并诱导神经胶质细胞凋亡。

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Con A急性肝炎模型[2]
小鼠灌胃100 μL水或Givinostat (ITF-2357) (5 mg/kg)， 1 h后静脉注射ConA 200 μg/只。对照组小鼠静脉注射生理盐水。如前所述，小鼠在24小时后放血以评估血清ALT水平（33,34）。如图15所示，经ITF2357预处理后，ALT水平降低80%以上。在另一项实验中，对口服ITF2357 1和10 mg/kg进行了比较。如图16所示，通过ALT水平测量，1 mg/kg剂量的ITF2357与10 mg/kg剂量的ITF2357在减少ConA型肝炎方面同样有效。

HDAC1–HDAC11 酶是重组人 HDAC。使用 Fluor de Lys 脱乙酰酶底物进行 HDAC1、HDAC2、HDAC3、HDAC6、HDAC10 和 HDAC11 活性测定。使用 Fluor de Lys Green 脱乙酰酶底物，测量 HDAC8 活性。使用 N-三氟乙酰基-L-赖氨酸进行 HDAC4、HDAC5、HDAC7 和 HDAC9 的测定。使用 25 μL Givinostat (ITF2357) 或 ITF3056 在 30°C 下在微量滴定板孔中进行重组酶的预孵育。短暂孵育后添加 25 μL 底物，并添加 50 μL 含有 2 μM Trichostatin A 的显色剂以产生荧光信号。底物浓度、测定缓冲液、孵育时间和酶量均针对每次测定进行了优化。在不存在 ITF3056 或 Givinostat 的情况下，使用酶加底物作为酶活性的阳性对照。 Victor 多标记读板机用于查找荧光信号[1]。

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玉米HDAC测定[2]
HD2， HD-1B和HD-1A从玉米中提取，用于评估Givinostat (ITF-2357)的组蛋白脱乙酰酶活性，如Koelle等人所述。

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细胞粗提物对总HDAC活性和蛋白质乙酰化的测定[2]
将人外周血单个核细胞（PBMCs）（见下文）在含有1% FCS和0.05% DMSO （vol/vol）的RPMI 1640培养基中以2.5 × 106个细胞/mL的浓度加入到50 mL的圆锥体管中，并与所述浓度的测试化合物（由0.05% DMSO组成）在37℃下孵育。60 min后，加入终浓度为10 ng/mL的LPS， 37℃孵育。孵育结束后，400g离心15 min，收集上清，- 80℃保存至测定TNFα，并用冰冷的磷酸盐缓冲液洗涤细胞2次。
将微球悬浮于200 μL改性裂解缓冲液（50 mM Tris HCl, pH 7.4, 1% NP-40, 0.25% na -脱氧胆酸盐，150 mM NaCl, 1 mM EDTA, 1 mM PMSF, 1 mM Na3VO4, 1 mM NaF）中，与可作为片剂的蛋白酶抑制剂混合，在4℃下悬浮30 min，得到粗提物。提取液在4℃下14000 rpm离心10 min澄清，上清液用于测定总HDAC活性和蛋白乙酰化。采用BCA蛋白测定试剂盒测定提取物的蛋白质含量。

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总HDAC活性测定[2]
如前所述，该分析是基于从肽底物释放的氚化乙酰基残基，内在标记为[3H]乙酸。本实验中使用的合成肽是组蛋白H4的n端序列（SGRGKGGKGLGKGGAKRHRC）。采用放射性标记法：将100 μg肽加入62.5 μL [3H]乙酸钠盐（5.0 mCi/0.5 mL乙醇，比活性5.1 Ci/mol）中。然后，加入5 μL BOP溶液（0.24 M BOP和0.2 M三甲胺乙腈）。得到的溶液在室温下轻度搅拌孵育过夜，然后将放射性标记的肽溶液上传到Microcon-SCX自旋柱上，之前用500 μL的10 mM HCl在甲醇中冲洗。用50 μL HCl 3N在50%异丙醇溶液中洗脱放射性标记肽。包含放射性标记的肽的洗脱方案提交到8个周期的有机溶剂萃取乙酸乙酯(8×1毫升)分离其余自由[3 h]醋酸。得到的水溶液在室温下真空离心干燥30 min，然后悬浮在200 μL蒸馏水中，分离成等分，在- 20℃保存。

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蛋白的乙酰化[2]
细胞粗提物的蛋白乙酰化用Western blotting测定。简单地说，将样品（200 μg/lane）通过SDS-PAGE（12.5%）分离，然后电转移到硝化纤维素膜上。膜用3%脱脂乳在磷酸盐缓冲液中饱和，并根据制造商的说明用抗乙酰赖氨酸单克隆抗体孵育。然后使用化学发光检测系统ECL Plus在x射线胶片上检测蛋白质条带。

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合成化合物抑制HDAC活性的酶促测定[2]
在细胞粗提液（5 μL）中加入100 μL底物（20万cpm）、40 μL缓冲液（50 mM Tris-HCl、pH 8.0、750 mM NaCl、5 mM PMSF、50%甘油）和95 μL蒸馏水。加入抑制HDAC的化合物（50 μL）。室温孵育过夜，在1 mL蒸馏水中加入50 μL含259 μL 37% HCl和28 μL乙酸的溶液，使反应猝灭。通过加入600 μL乙酸乙酯有机萃取分离底物释放的[3H]乙酰基残基，在标准闪烁液中加入200 μL有机相，用β -计数器测定放射性。hdac的抑制作用表现为抑制50%对照活性的浓度（通过将含有抑制剂的样品与仅含有细胞粗提物的样品的放射性进行比较）。

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酶法测定HDAC活性[1]
重组人HDAC酶（HDAC1-10）购自BPS。采用氟绿脱乙酰酶底物检测HDAC8活性。利用Nϵ-Trifluoroacetyl-l-lysine检测HDAC 4、5、7、9的活性。重组酶与Givinostat (ITF-2357)或ITF3056在30°C下以25 μl的体积在微滴板孔中预孵育。短暂孵育后，加入25 μl底物，添加50 μl显影剂（含2 μm曲古菌素a的Fluor de Lys显影剂）产生荧光信号。每个实验对酶的用量、孵育次数、实验缓冲液和底物浓度进行优化。酶活性阳性对照为酶加底物，不含ITF2357和ITF3056。荧光信号检测使用一个维克多multilabel板读者。

在补充有 10% 胎牛血清的 DMEM 中培养 24 小时后，将含有 JS-1 细胞的 30 个孔分成两组。将 Givinostat (ITF-2357)添加到第一组的培养基中，终浓度为 0 nM、125 nM、250 nM、500 nM 和 1000 nM。在第二组中，同时添加适当浓度的 100 nM LPS 溶液和 Givinostat (ITF-2357)。对于每组，进行三次重复。在 37°C 和 5% CO₂ 下接种 24 小时后，每孔 (100 μL) 中孵育 10 μL CCK-8 溶液。将板在 37°C 下孵育一小时后，使用酶标仪测量 450 nm 处的吸光度[2]。

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采用细胞计数试剂盒-8法和流式细胞术观察Givinostat (ITF-2357)处理后肝星状细胞增殖、凋亡和细胞周期的变化。Western blot观察Givinostat (ITF-2357)的肝星状细胞中p21、p57、CDK4、CDK6、cyclinD1、caspase-3、caspase-9的表达变化。采用划痕法分析吉维司他对细胞迁移的影响。采用激光共聚焦显微镜观察吉维司他对JS-1细胞活性氧谱、线粒体膜电位和线粒体通透性过渡孔开度的影响。[3]

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Caspase-1活性测定[1]
分别用LPS （10 ng/ml）刺激4和24 h。根据Givinostat (ITF-2357)和ITF3056对LPS诱导的IL-1β产生和分泌的抑制作用，选择25 nm ITF2357和1000 nm ITF3056作为最佳浓度来评估其对caspase-1活性的影响。在LPS前30分钟加入ITF2357 （25 nm）或ITF3056 （1000 nm）。清除上清后，使用含有蛋白酶抑制剂混合物的放射免疫沉淀测定缓冲液裂解细胞，并在4°C下以12,000 rpm离心20分钟。用Bio-Rad法测定上清液的蛋白质含量。用荧光底物A2452对蛋白进行caspase-1活性处理。荧光以1 μg样品/min（荧光/μg/min）产生的任意荧光单位报道。数据表示为LPS刺激的pbmc与类似物孵育的裂解物中caspase-1活性的百分比变化，LPS的裂解物仅设为100%。

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细胞毒性测定[1]
采用三种方法比较Givinostat (ITF-2357)和ITF3056的细胞毒作用。将新鲜获得的pbmc在96平底孔板中培养24小时，LPS （10 ng/ml）存在，不含胎牛血清，如前所述，使用LDH细胞毒性测定试剂盒，在上清中测量LDH释放。乳酸脱氢酶释放百分比根据制造商的说明计算。此外，在96平底孔板中，在LPS (10 ng/ml)（40万个细胞/ml）的存在下，用添加1% FCS的RPMI培养pbmc 24小时，评估细胞活力。孵育结束时，根据制造商的说明，通过CellTiter 96®水溶液细胞增殖试验测定细胞活力。我们还评估了从人柠檬酸血中分离的灰白色被细胞PBMC的细胞活力。将从褐皮中分离的pbmc以500000个细胞/孔（96平底孔板）在含10% FCS的RPMI中播种，并使用如上所述的CellTiter法在ITF2357或ITF3056浓度增加的条件下孵育72小时。

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Annexin V染色单核细胞凋亡[1]
通过磁分离从新鲜pbmc中分离单核细胞，并在含有10% FCS的RPMI中重悬。纯化的单核细胞以250000个细胞/孔的速度接种，在增加Givinostat (ITF-2357)或ITF3056浓度的LPS （10 ng/ml）中孵育。24小时后，按照制造商的说明，用膜联蛋白V-FLUOS 和碘化丙啶（PI）标记细胞。流式细胞术测定膜联蛋白V阳性和膜联蛋白V/ pi双阳性细胞的百分比。

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Caspase-3/7对单核细胞凋亡的检测[1]
如上所述分离的单核细胞，在96平底孔板中以50,000个细胞/孔的速度孵育，用LPS （10 ng/ml）增加Givinostat (ITF-2357)或ITF3056的浓度，孵育24小时。然后用Apo-ONE均相caspase-3/7法测定caspase-3/7的活性，用荧光板阅读器检测荧光量。

Mice: For a minimum of five days prior to usage, C57BL/6 mice are kept in the animal facility. Intraperitoneal injection of ITF3056 and oral administration of Givinostat (ITF-2357) at a dose of 10 mg/kg are used in the comparative study. LPS from Salmonella typhimurium is administered intraperitoneally to the animals at a dose of 2.5 mg/kg one hour after the compounds are administered. Serum is collected and kept at -80°C until further examination of cytokine production, and mice are sacrificed 90 minutes after the LPS treatment.

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Mice for LPS induction of serum cytokines were BALB/c, whereas those for anti-CD3-induced cytokines were CD1. Mice for concanavalin A (Con A)–induced acute hepatitis were BALB C or C57Bl6 obtained from Jackson Laboratories. Mice were given 100 μL water or Givinostat (ITF-2357) in water by gavage and, after 60 min, were injected intraperitoneally with LPS (30 mg/kg) or intravenously with anti-mouse CD3 (10 μg/mouse) or intravenously with 200 μg/mouse of Con A into a tail vein. Control mice received an intraperitoneal injection of saline or intravenous injection of saline. For LPS, mice were killed by anesthetic overdose, and blood was obtained at 90 min and 6 h. For anti-mouse CD3, mice were killed by anesthetic overdose, and blood was obtained at 90 min. Mice were bled 24 h later for evaluation of serum ALT levels as described previously. [2] C57BL/6 mice were housed in the animal facility for at least 5 days before use. For the comparison study, Givinostat (ITF-2357) at 10 mg/kg was administered orally as reported previously, and ITF3056 was injected intraperitoneally. One hour after administration of the compounds, the animals were treated intraperitoneally with LPS from Salmonella typhimurium at a dose of 2.5 mg/kg. 90 min after the LPS treatment, mice were sacrificed, and sera were collected and stored at −80 °C until further analysis of cytokine productions. A dose-response study of ITF3056 at 4, 8, and 16 mg/kg was performed in mice injected intraperitoneallly with LPS from E. coli (055:B5) (Sigma-Aldrich) at 10 mg/kg. After 4 h, the serum was collected for cytokine levels. Another dose study of ITF3056 at 1 and 5 mg/kg used a lower dose of LPS (2.5 mg/kg) given intraperitoneally after ITF3056 injection. 4 h later, the mice were sacrificed, and blood was collected. Blood was collected in EDTA, separated into plasma for cytokine levels, or diluted in RPMI for whole blood culture as described previously. [1]

[1]. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78.

[2]. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

[3]. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39.

Givinostat hydrochloride is the hydrochloride salt of givinostat. It has a role as an angiogenesis inhibitor, an anti-inflammatory agent, an antineoplastic agent, an apoptosis inducer and an EC 3.5.1.98 (histone deacetylase) inhibitor. It contains a givinostat(1+).
Histone Deacetylase Inhibitor is any substance that inhibits histone deacetylase, an enzyme that catalyzes the removal of acetyl groups from core histones. Inhibition of histone deacetylase can result in hyperacetylation of histones, with an effect on gene expression and cell differentiation.

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Givinostat is a member of the class of naphthalenes that is naphthalene substituted by ({[4-(hydroxycarbamoyl)phenyl]carbamoyl}oxy)methyl and (diethylamino)methyl groups at positions 2 and 6, respectively. It is a histone deacetylase inhibitor indicated for individuals diagnosed with Duchenne muscular dystrophy. It has a role as an EC 3.5.1.98 (histone deacetylase) inhibitor, an anti-inflammatory agent, an angiogenesis inhibitor, an antineoplastic agent and an apoptosis inducer. It is a carbamate ester, a member of naphthalenes, a tertiary amino compound, a hydroxamic acid and a member of benzenes. It is a conjugate base of a givinostat(1+).
Givinostat has been used in trials studying the treatment of Polycythemia Vera, Juvenile Idiopathic Arthritis, Duchenne Muscular Dystrophy (DMD), Chronic Myeloproliferative Neoplasms, and Polyarticular Course Juvenile Idiopathic Arthritis.
Givinostat is an orally bioavailable hydroxymate inhibitor of histone deacetylase (HDAC) with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. Givinostat inhibits class I and class II HDACs, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. At low, nonapoptotic concentrations, this agent inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), IL-6 and interferon-gamma. Givinostat has also been shown to activate the intrinsic apoptotic pathway, inducing apoptosis in hepatoma cells and leukemic cells. This agent may also exhibit anti-angiogenic activity, inhibiting the production of angiogenic factors such as IL-6 and vascular endothelial cell growth factor (VEGF) by bone marrow stromal cells.
See also: Givinostat hydrochloride (annotation moved to).

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Drug Indication
Treatment of Duchenne muscular dystrophy
Juvenile idiopathic arthritis.

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ITF2357 (generic givinostat) is an orally active, hydroxamic-containing histone deacetylase (HDAC) inhibitor with broad anti-inflammatory properties, which has been used to treat children with systemic juvenile idiopathic arthritis. ITF2357 inhibits both Class I and II HDACs and reduces caspase-1 activity in human peripheral blood mononuclear cells and the secretion of IL-1β and other cytokines at 25-100 nm; at concentrations >200 nm, ITF2357 is toxic in vitro. ITF3056, an analog of ITF2357, inhibits only HDAC8 (IC50 of 285 nm). Here we compared the production of IL-1β, IL-1α, TNFα, and IL-6 by ITF2357 with that of ITF3056 in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), heat-killed Candida albicans, or anti-CD3/anti-CD28 antibodies. ITF3056 reduced LPS-induced cytokines from 100 to 1000 nm; at 1000 nm, the secretion of IL-1β was reduced by 76%, secretion of TNFα was reduced by 88%, and secretion of IL-6 was reduced by 61%. The intracellular levels of IL-1α were 30% lower. There was no evidence of cell toxicity at ITF3056 concentrations of 100-1000 nm. Gene expression of TNFα was markedly reduced (80%), whereas IL-6 gene expression was 40% lower. Although anti-CD3/28 and Candida stimulation of IL-1β and TNFα was modestly reduced, IFNγ production was 75% lower. Mechanistically, ITF3056 reduced the secretion of processed IL-1β independent of inhibition of caspase-1 activity; however, synthesis of the IL-1β precursor was reduced by 40% without significant decrease in IL-1β mRNA levels. In mice, ITF3056 reduced LPS-induced serum TNFα by 85% and reduced IL-1β by 88%. These data suggest that specific inhibition of HDAC8 results in reduced inflammation without cell toxicity.[1]

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We studied inhibition of histone deacetylases (HDACs), which results in the unraveling of chromatin, facilitating increased gene expression. ITF2357, an orally active, synthetic inhibitor of HDACs, was evaluated as an anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated cultured human peripheral blood mononuclear cells (PBMCs), ITF2357 reduced by 50% the release of tumor necrosis factor-alpha (TNFalpha) at 10 to 22 nM, the release of intracellular interleukin (IL)-1alpha at 12 nM, the secretion of IL-1beta at 12.5 to 25 nM, and the production of interferon-gamma (IFNgamma) at 25 nM. There was no reduction in IL-8 in these same cultures. Using the combination of IL-12 plus IL-18, IFNgamma and IL-6 production was reduced by 50% at 12.5 to 25 nM, independent of decreased IL-1 or TNFalpha. There was no evidence of cell death in LPS-stimulated PBMCs at 100 nM ITF2357, using assays for DNA degradation, annexin V, and caspase-3/7. By Northern blotting of PBMCs, there was a 50% to 90% reduction in LPS-induced steady-state levels of TNFalpha and IFNgamma mRNA but no effect on IL-1beta or IL-8 levels. Real-time PCR confirmed the reduction in TNFalpha RNA by ITF2357. Oral administration of 1.0 to 10 mg/kg ITF2357 to mice reduced LPS-induced serum TNFalpha and IFNgamma by more than 50%. Anti-CD3-induced cytokines were not suppressed by ITF2357 in PBMCs either in vitro or in the circulation in mice. In concanavalin-A-induced hepatitis, 1 or 5 mg/kg of oral ITF2357 significantly reduced liver damage. Thus, low, nonapoptotic concentrations of the HDAC inhibitor ITF2357 reduce pro-inflammatory cytokine production in primary cells in vitro and exhibit anti-inflammatory effects in vivo.[2]

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Aim: To explore the effect of the histone deacetylase inhibitor givinostat on proteins related to regulation of hepatic stellate cell proliferation. Methods: The cell counting kit-8 assay and flow cytometry were used to observe changes in proliferation, apoptosis, and cell cycle in hepatic stellate cells treated with givinostat. Western blot was used to observe expression changes in p21, p57, CDK4, CDK6, cyclinD1, caspase-3, and caspase-9 in hepatic stellate cells exposed to givinostat. The scratch assay was used to analyze the effect of givinostat on cell migration. Effects of givinostat on the reactive oxygen species profile, mitochondrial membrane potential, and mitochondrial permeability transition pore opening in JS-1 cells were observed by laser confocal microscopy. Results: Givinostat significantly inhibited JS-1 cell proliferation and promoted cell apoptosis, leading to cell cycle arrest in G0/G1 phases. Treatment with givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas expression of p21 and p57 was significantly increased. The givinostat-induced apoptosis of hepatic stellate cells was mainly mediated through p38 and extracellular signal-regulated kinase 1/2. Givinostat treatment increased intracellular reactive oxygen species production, decreased mitochondrial membrane potential, and promoted mitochondrial permeability transition pore opening. Acetylation of superoxide dismutase (acetyl K68) and nuclear factor-κB p65 (acetyl K310) was upregulated, while there was no change in protein expression. Moreover, the notable beneficial effect of givinostat on liver fibrosis was also confirmed in the mouse models. Conclusion: Givinostat has antifibrotic activities via regulating the acetylation of nuclear factor-κB and superoxide dismutase 2, thus inhibiting hepatic stellate cell proliferation and inducing apoptosis.[3]

C24H27N3O4.HCL

457.96

457.177

C, 62.95; H, 6.16; Cl, 7.74; N, 9.18; O, 13.97

199657-29-9

Givinostat;497833-27-9;Givinostat hydrochloride monohydrate;732302-99-7

10095659

White to off-white solid powder

5.815

90.9

4

5

9

32

575

0

Cl[H].O(C(N([H])C1C([H])=C([H])C(C(N([H])O[H])=O)=C([H])C=1[H])=O)C([H])([H])C1C([H])=C([H])C2C([H])=C(C([H])=C([H])C=2C=1[H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H]

QKSGNWJOQMSBEP-UHFFFAOYSA-N

InChI=1S/C24H27N3O4.ClH/c1-3-27(4-2)15-17-5-7-21-14-18(6-8-20(21)13-17)16-31-24(29)25-22-11-9-19(10-12-22)23(28)26-30;/h5-14,30H,3-4,15-16H2,1-2H3,(H,25,29)(H,26,28);1H

[6-(diethylaminomethyl)naphthalen-2-yl]methyl N-[4-(hydroxycarbamoyl)phenyl]carbamate;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)