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)

Givinostat (ITF2357) effectively inhibits the production of IL-1β induced by LPS in its entirety, as opposed to ITF3056's reduction. Givinostat inhibits IL-1β secretion by over 70% at concentrations of 25, 50, and 100 nM. When TLR agonists or the combination of IL-12 and IL-18 are used to stimulate PBMCs, glinotanost inhibits the production of IL-6. Givinostat at 50 nM causes IL-6 secretion to drop to 50%, but at 100 and 200 nM, there is no reduction[1]. Using the CCK-8 assay, ginostat (ITF-2357) inhibits the growth of JS-1 cells in a concentration-dependent manner. Proliferation of JS-1 cells is significantly inhibited when treated with Givinostat (ITF-2357) at concentrations ≥500 nM. There is a significant difference in the cell inhibition rate between the group that received LPS treatment without any treatment and the group that received Givinostat (ITF-2357) ≥250 nM in addition[2].

Givinostat (ITF2357), a positive control, lowers serum TNFα by 60% when administered at a dose of 10 mg/kg. TNFα in circulation is markedly decreased by almost 90% with pretreatment with Givinostat (ITF-2357), starting at 0.1 mg/kg. A larger dose of LPS (10 mg/kg) is injected, and blood is taken after 4 hours to obtain a notable increase in serum IL-1β production[1].

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Con A Model of Acute Hepatitis[2]
Mice were given 100 μL water or Givinostat (ITF-2357) (5 mg/kg) by gavage and, after 1 h, injected intravenously with 200 μg/mouse of ConA. Control mice received an intravenous injection of saline. Mice were bled 24 h later for evaluation of serum ALT levels as described previously (33,34). As shown in Figure 15, ALT levels were reduced by more than 80% by ITF2357 pretreatment. In another experiment, a comparison was made between 1 and 10 mg/kg of oral ITF2357. As shown in Figure 16, a dose of 1 mg/kg ITF2357 was as effective as a dose of 10 mg/kg in reducing ConA hepatitis as measured by ALT levels.

The enzymes HDAC1–HDAC11 are recombinant human HDACs. Assays for HDAC1, HDAC2, HDAC3, HDAC6, HDAC10, and HDAC11 activity are conducted using the Fluor de Lys deacetylase substrate. With Fluor de Lys Green deacetylase substrate, HDAC8 activity is measured. Assays for HDAC4, HDAC5, HDAC7, and HDAC9 are performed using N-trifluoroacetyl-L-lysine. Pre-incubation of recombinant enzymes is carried out in microtiter plate wells using 25 μL of Givinostat (ITF2357) or ITF3056 at 30°C. 25 μL of substrate is added after a brief incubation period, and 50 μL of developer containing 2 μM Trichostatin A is added to produce the fluorescent signal. The concentration of the substrates, assay buffer, incubation times, and enzyme quantity are all optimized for each assay. Enzyme plus substrate was used as a positive control for enzyme activity in the absence of ITF3056 or Givinostat. The Victor multilabel plate reader is used to find the fluorescence signal[1].

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Maize HDAC Assays [2]
HD2, HD-1B, and HD-1A from maize and used to assess the histone deacetylase activity of Givinostat (ITF-2357) as described in Koelle et al.

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Cellular Crude Extract for Total HDAC Activity and Protein Acetylation Determinations [2]
Human peripheral blood mononuclear cells (PBMCs) (see below) were added to 50-mL conical tubes at a concentration of 2.5 × 106 cell/mL in RPMI 1640 medium with 1% FCS and 0.05% DMSO (vol/vol) and incubated at 37° C with the test compounds (constituted in DMSO 0.05%) at the stated concentrations. After 60 min, LPS was added at final concentration of 10 ng/mL and the cells were incubated at 37° C. At the end of incubation times, the cells were centrifuged at 400g for 15 min, the supernatant was collected and stored at −80° C until TNFα determination, and the cells were washed twice with ice-cold phosphate buffer.
Crude extracts were obtained by suspending the pellet in 200 μL modified lysis buffer (50 mM Tris HCl, pH 7.4, 1% NP-40, 0.25% Na-deoxycholate, 150 mM NaCl, 1 mM EDTA, 1 mM PMSF, 1 mM Na3VO4, 1 mM NaF) together with a cocktail of protease inhibitors available as tablets for 30 min at 4° C. The cells were disrupted by sonication, after which the extract was clarified by centrifugation at 14,000 rpm for 10 min at 4° C. The supernatant was used for determination of total HDAC activity and protein acetylation. Protein content of the extract was determined using the BCA protein assay kit.

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Total HDAC Activity Assay [2]
The assay was adapted based on the release of tritiated acetyl residues from a peptide substrate intrinsically labeled with [3H]acetic acid, as described previously. The synthetic peptide used in this assay was the N-terminal sequence (SGRGKGGKGLGKGGAKRHRC) of histone H4. Radiolabeling of the peptide was done as follows: 100 μg peptide was added to 62.5 μL [3H]acetic acid sodium salt (5.0 mCi/0.5 mL in ethanol, specific activity 5.1 Ci/mole). Thereafter, 5 μL BOP solution (0.24 M BOP and 0.2 M trimethylamine in acetonitrile) was added. The resulting solution was incubated overnight at room temperature with mild agitation, and the radiolabeled peptide solution was loaded onto a Microcon-SCX spin column previously rinsed with 500 μL of 10 mM HCl in methanol. The eluate was separated by centrifugation of the column (2,000g for 60 s). The radiolabeled peptide was eluted with 50 μL HCl 3N in 50% isopropanol. The eluting solution containing the radiolabeled peptide was submitted to 8 cycles of organic solvent extraction (8 × 1 mL of ethylacetate) to separate the remaining free [3H]acetic acid. The resulting aqueous solution was dried by centrifugation under vacuum for 30 min at room temperature and then suspended in 200 μL distilled water, separated into aliquot, and stored at −20° C.

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Acetylation of Proteins [2]
Acetylation of proteins was determined by Western blotting of crude cellular extracts. Briefly, the samples (200 μg/lane) were separated by SDS-PAGE (12.5%) and then electrically transferred onto nitrocellulose membranes. The membranes were saturated with 3% nonfat milk in phosphate buffer and incubated with anti-acetyl-lysine monoclonal antibody according to manufacturer’s instructions. Protein bands were then detected using the chemiluminescence detection system ECL Plus onto x-ray film.

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Enzymatic Assay for HDAC Inhibitory Activity of Synthetic Compounds [2]
The assay was performed by adding 100 μL substrate (200,000 cpm) with 40 μL buffer (50 mM Tris-HCl, pH 8.0, 750 mM NaCl, 5 mM PMSF, 50% glycerol) and 95 μL distilled water to the crude cellular extract (5 μL). Compounds for testing of HDAC inhibition (50 μL) were added. The mixture was incubated overnight at room temperature and the reaction quenched by adding 50 μL of a solution containing 259 μL HCl 37% and 28 μL acetic acid in 1 mL distilled water. The [3H]acetyl residues released from the substrate were separated by organic extraction by adding 600 μL of ethyl acetate, 200 μL of the organic phase was added to standard scintillation fluid, and radioactivity was measured by a beta-counter. Inhibition of HDACs was expressed as the concentration inhibiting 50% of the control activity (by comparing the radioactivity of the samples containing inhibitors to that of the control containing cellular crude extract alone).

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Enzymatic Assay for HDAC Activity [1]
Recombinant human HDAC enzymes (HDAC1–10) were purchased from BPS. HDAC8 activity was assayed using Fluor de Lys Green deacetylase substrate. Nϵ-Trifluoroacetyl-l-lysine was used to assay activity of HDAC 4, 5, 7, and 9. Recombinant enzymes were preincubated with Givinostat (ITF-2357) or ITF3056 at 30 °C in a volume of 25 μl in wells of a microtiter plate. After a brief incubation, 25 μl of substrate was added, and the fluorescent signal was generated by the addition of 50 μl of developer (Fluor de Lys Developer containing 2 μm Trichostatin A. For each assay, the amount of enzyme, incubation times, assay buffer, and concentration of the substrates were optimized. Positive control for enzyme activity consisted of enzyme plus substrate without ITF2357 or ITF3056. The fluorescence signal was detected using a Victor multilabel plate reader.

Following a 24-hour culture period in DMEM supplemented with 10% fetal bovine serum, 30 wells containing JS-1 cells are split into two groups.Givinostat (ITF-2357) is added to the culture medium in the first group at final concentrations of 0 nM, 125 nM, 250 nM, 500 nM, and 1000 nM. In the second group, 100 nM of LPS solution is added concurrently with Givinostat at appropriate concentrations. For every group, three replicates are carried out. Following a 24-hour inoculation period at 37°C and 5% CO₂, 10 μL of CCK-8 solution is incubated in each well (100 μL). A microplate reader is used to measure the absorbance at 450 nm after the plates are incubated for one hour at 37°C[2].

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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 (ITF-2357). 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 (ITF-2357). 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.[3]

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Caspase-1 Activity Assay [1]
Human PBMCs from four donors were stimulated with LPS (10 ng/ml) for 4 and 24 h. Based on the reduction by Givinostat (ITF-2357) and ITF3056 of LPS-induced IL-1β production and secretion, 25 nm Givinostat (ITF-2357) and 1000 nm ITF3056 were selected as the optimal concentrations to assess effects on caspase-1 activity. ITF2357 (25 nm) or ITF3056 (1000 nm) were added 30 min prior to LPS. After the supernatant was removed, the cells were lysed using radioimmune precipitation assay buffer containing a mixture of protease inhibitors and centrifuged at 12,000 rpm for 20 min at 4 °C. The supernatants were assayed for protein content using the Bio-Rad method. Protein was processed for caspase-1 activity using the fluorogenic substrate A2452. The fluorescence was reported as arbitrary fluorescence units generated by 1 μg of sample/min (fluorescence/μg/min). The data were expressed as the percentage change in caspase-1 activity present in the lysates of LPS-stimulated PBMCs incubated with analogues, with the lysates from LPS only set as 100%.

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Assays for Cytotoxicity [1]
Three assays were used to compare the cytotoxic effects of Givinostat (ITF-2357) with those of ITF3056. LDH release was measured in supernatants from freshly obtained PBMCs cultured in 96-flat bottom well plates for 24 h in the presence of LPS (10 ng/ml) without fetal calf serum as described previously using the LDH cytotoxicity assay kit. The percentage of LDH release was calculated according to the manufacturer's instructions. In addition, cell viability was assessed in PBMCs cultured in RPMI supplemented with 1% FCS in the presence of LPS (10 ng/ml) at 400,000 cells/ml in a 96-flat bottom well plate for 24 h. At the end of incubation, cell viability was determined by the CellTiter 96® Aqueous One solution cell proliferation assay according to the manufacturer's instructions. We also assessed cell viability in PBMC isolated from buffy coat cells of human citrated blood. PBMCs isolated from buffy coats were seeded at 500,000 cells/well (96-flat bottom well plate) in RPMI with 10% FCS and incubated for 72 h in the presence of increasing concentrations of ITF2357 or ITF3056 using the CellTiter assay as described above.

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Annexin V Staining for Monocyte Apoptosis [1]
Monocytes were isolated from fresh PBMCs by magnetic separation and resuspended in RPMI containing 10% FCS. Purified monocytes were seeded at 250,000 cells/well and incubated in the presence of increasing concentrations of ITF2357 or ITF3056 with LPS (10 ng/ml). After 24 h, the cells were labeled with annexin V-FLUOS and propidium iodide (PI) following the manufacturer's instructions. The percentages of annexin V-positive and annexin V/PI-double-positive cells were determined by flow cytometric analysis.

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Caspase-3/7 Determinations for Monocyte Apoptosis [1]
Monocytes, isolated as described above, were incubated at 50,000 cells/well in 96-flat bottom well plates in the presence of increasing concentrations of Givinostat (ITF-2357) or ITF3056 with LPS (10 ng/ml) for 24 h of incubation. The activity of caspase-3/7 was then determined by the Apo-ONE homogeneous caspase-3/7 assay, and the amount of fluorescence was detected by a fluorimetric plate reader.

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

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)