Histone Deacetylases (HDACs); endoplasmic reticulum (ER) stress
Histone deacetylases (HDACs), with selective activity against HDAC 2, 3 and 8 [2]

Histone H3 lysine 9 and 14 (H3K9/K14) acetylation status [2]

NF-κB (inhibits DNA binding activity) [3]

Autophagy pathway (ATG7-dependent) [3]

At a concentration of 2 mM, the HDAC inhibitor 4-phenylbutyric acid (4-PBA) stops the growth of NSCLC cell lines. Phenylbutyric acid and ciglitazone together can improve cancer cell growth inhibition [1]. 4-ASFV infection is inhibited by phenylbutyric acid (0–5 mM) in a dose-dependent manner. In addition to preventing ASFV-induced H3K9/K14 hypoacetylation, benzoenebutyric acid also suppresses late protein synthesis. Together, phenylbutyric acid and enrofloxacin prevent ASFV replication [2]. When bafilomycin A1 was added, LC3II accumulated; however, 4-phenylbutyric acid dramatically decreased this accumulation. Phenylbutyric acid counteracted the 48-hour decline in p62 levels caused by LPS stimulation. After 48 hours, the percentage of AVO cells induced by LPS rose, whereas 4-phenylbutyric acid markedly reduced this percentage. Particularly, following treatment with phenylbutyric acid, the proportion of cells exhibiting AVO dropped from 61.6% to 53.1%, indicating that 4-phenylbutyric acid suppresses autophagy induced by lipopolysaccharide (LPS). The positive control for autophagy inhibition employed in this study was bafilomycin A1. The percentage of LPS-induced AVO cells was decreased by bafilomycin A1 treatment. In ATG7 knockdown, there was no phenylbutyric acid treatment-induced decrease in OC area or fusion index. Phenylbutyric acid's inhibitory effect on LPS-induced effects is totally eliminated when NF-κB is inhibited using BAY 11-7082 and JSH23, which also lowers LC3 II levels following LPS stimulation [3].

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At non-cytotoxic concentration (5 mM), 4-Phenylbutyric acid completely abolished ASFV replication in Vero E6 cells at 24 and 48 hours post-infection (MOI=0.1), while other HDAC inhibitors (VPA, TSA, SAHA) only reduced viral titers by 0.5-0.8 log. The antiviral effect was dose-dependent. [2]
- 4-Phenylbutyric acid did not inactivate extracellular ASFV particles when incubated for 1 or 12 hours at 37°C, suggesting its mechanism is not via direct disruption of viral envelope integrity. [2]
- 4-Phenylbutyric acid inhibited the synthesis of intermediate/late viral proteins (Vp72 and Vp54) in ASFV-infected Vero cells, as shown by Western blot. Immunofluorescence revealed a reduction in the number (-81.02% at 24 hpi; -87.46% at 48 hpi) and size of viral factories. [2]
- 4-Phenylbutyric acid reversed the ASFV-induced hypoacetylation status of histone H3K9/K14, promoting a hyperacetylated state compatible with open chromatin, as detected by Western blot. [2]
- A synergistic antiviral effect was observed: half-protective concentrations of 4-Phenylbutyric acid (2.5 mM) and enrofloxacin (25 μg/ml) completely abolished ASFV replication, whereas each drug alone only reduced viral titers by -1.6 log and -2.2 log, respectively. [2]
- In osteoclast (OC) precursors (BMMs treated with RANKL then LPS), 4-Phenylbutyric acid (0.5 and 1 mM) significantly reduced OC area, maximum diameter, and fusion index without affecting OC number or cell viability (MTT assay). It downregulated mRNA expression of DC-STAMP, ATP6v0d2, and calcitonin receptor, but not TRAP or NFAT2. It also decreased secreted cathepsin K activity and reduced bone resorption pit area on dentine slices. [3]
- 4-Phenylbutyric acid (1 mM) attenuated LPS-induced autophagy in OCs, as shown by decreased LC3II accumulation, increased p62 levels, and a reduction in the percentage of acidic vesicular organelle (AVO)-containing cells (from 61.6% to 53.1% via flow cytometry). Silencing of ATG7 abolished the inhibitory effects of 4-PBA on OC area and fusion. [3]
- 4-Phenylbutyric acid (0.5-1 mM) impaired LPS-induced NF-κB DNA binding activity in a dose-dependent manner (EMSA). Pharmacological inhibitors of NF-κB (BAY 11-7082, JSH23) mimicked and blocked the further effect of 4-PBA on OC size, fusion, and LC3II level, indicating that the effect on autophagy is mediated via NF-κB inhibition. [3]

LPS significantly decreased bone volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD) as compared to PBS alone. Trabecular space (Tb. Sp.) increased. LPS-induced bone loss is decreased by 4-phenylbutyric acid (4-PBA). 4-BMD, BV/TV, and Tb. Th were all elevated after phenylbutyric acid treatment. besides decreasing the rise in Tb in comparison to LPS alone. Sp., but when phenylbutyric acid was administered to mice alone, no alterations were seen. Phenylbutyric acid treatment of LPS-treated mice also resulted in a considerable decrease in OC.S/BS as measured by TRAP staining. However, OC.N/BS tended to decline in mice treated with LPS and phenylbutyric acid, albeit not in a statistically significant way. According to these findings, phenylbutyric acid causes OC in LPS-treated mice to shrink in size as opposed to increasing in number. In line with these results, phenylbutyric acid therapy of LPS-injected mice resulted in a decrease in blood CTX-1, a marker of bone resorption in vivo that was enhanced by LPS treatment. In contrast to LPS alone, phenylbutyric acid therapy did not substantially alter serum levels of osteocalcin and ALP, two indicators of bone formation in vivo. Moreover, phenylbutyric acid can lessen the rise in serum MCP-1 that is brought on by LPS, suggesting that it can lessen systemic inflammation brought on by LPS [3].

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In a mouse model of LPS-induced bone loss (C57BL/6J female mice, 10-week-old), intraperitoneal administration of 4-Phenylbutyric acid (240 mg/kg/day for 3 weeks) significantly protected against bone loss. Micro-CT analysis showed that 4-PBA increased bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular thickness (Tb.Th), while decreasing trabecular space (Tb.Sp.) compared to LPS alone. The protective effect was maximal at 240 mg/kg compared to 120 and 500 mg/kg. [3]
- 4-Phenylbutyric acid treatment in LPS-injected mice reduced the osteoclast surface per bone surface (OC.S/BS) as assessed by TRAP staining, and decreased serum levels of collagen type I fragments (CTX-1, a bone resorption marker) and MCP-1 (a systemic inflammation marker), but did not affect serum alkaline phosphatase (ALP) or osteocalcin (bone formation markers). [3]

African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study. Results showed that the sodium phenylbutyrate fully abrogates the ASFV replication, whereas the valproic acid leads to a significant reduction of viral progeny at 48h post-infection (-73.9%, p=0.046), as the two pan-HDAC inhibitors tested (Trichostatin A: -82.2%, p=0.043; Vorinostat: 73.9%, p=0.043). Further evaluation showed that protective effects of NaPB are dose-dependent, interfering with the expression of late viral genes and reversing the ASFV-induced histone H3 lysine 9 and 14 (H3K9K14) hypoacetylation status, compatible to an open chromatin state and possibly enabling the expression of host genes non-beneficial to infection progression. Additionally, a synergic antiviral effect was detected when NaPB is combined with an ASFV-topoisomerase II poison (Enrofloxacin). Altogether, our results strongly suggest that cellular HDACs are involved in the establishment of ASFV infection and emphasize that further in vivo studies are needed to better understand the antiviral activity of HDAC inhibitors[2].

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NF-κB DNA binding activity assay (EMSA): Nuclear extracts were prepared from RANKL-pretreated pre-osteoclasts stimulated with LPS (100 ng/ml) for 1 hour in the presence or absence of 4-Phenylbutyric acid (0.5 or 1 mM). Binding reactions were performed with biotin-labeled NF-κB oligonucleotide probe, poly(dI-dC), Nonidet P-40, MgCl2, EDTA, and glycerol. Samples were resolved on native 6% polyacrylamide gels, transferred to nylon membranes, crosslinked, and detected using HRP-conjugated streptavidin. A 100-fold excess of unlabeled probe was used as a competition control. NF-Y DNA binding was used as a loading control. 4-Phenylbutyric acid dose-dependently reduced NF-κB DNA binding activity. [3]
- Cathepsin K activity assay: Conditioned medium from mature osteoclasts (generated from pre-OCs treated with M-CSF and LPS for 48h, with or without 4-Phenylbutyric acid at 1 mM) was collected. Secreted cathepsin K activity was measured using a fluorescence-based assay with a cathepsin K substrate (LR-AFC). Released AFC was quantified using a fluorescence plate reader. 4-Phenylbutyric acid significantly decreased LPS-induced cathepsin K secretion. [3]

Nanomolar concentrations of trichostatin A induced growth arrest in five of seven NSCLC cell lines, whereas sodium phenylbutyrate (PB) was markedly less potent. In adenocarcinomas, trichostatin A up-regulated general differentiation markers (gelsolin, Mad, and p21/WAF1) and down-regulated markers of the type II pneumocyte progenitor cell lineage (MUC1 and SP-A), indicative of a more mature phenotype. PB had a similar effect. Simultaneous treatment with a PPARgamma ligand and PB enhanced the growth inhibition in adenocarcinomas but not in nonadenocarcinomas. Growth arrest was accompanied by markedly decreased cyclin D1 expression but not enhanced differentiation[1].

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Cell viability assay (Trypan blue exclusion): Vero E6 cells were seeded in 24-well plates and treated with various concentrations of 4-Phenylbutyric acid for 72 hours. A representative sample of cells (supernatant and adherent) was diluted 1:1 with 0.4% trypan blue solution. Dead cells stained blue, while viable cells remained unstained. At least 200 cells were counted per sample in three independent experiments. The concentration of 5 mM NaPB was found to be non-cytotoxic. [2]
- Viral infection and titer determination (TCID50): Vero cells were treated with 4-Phenylbutyric acid (5 mM) 12 hours before ASFV infection (MOI=0.1). After 1-hour adsorption, inoculum was removed, cells washed, and fresh medium with drug added. At 24 and 48 hpi, cultures were subjected to three freeze-thaw cycles, and viral yields were determined by TCID50 titration using the Spearman-Kärber method. [2]
- Western blotting: Mock-infected or ASFV-infected Vero cells were lysed in modified RIPA buffer with protease and phosphatase inhibitors. Whole-cell lysates were subjected to SDS-PAGE (4-15% gradient gel), transferred to nitrocellulose membranes, blocked with BSA in TBS-T, and incubated with primary antibodies (anti-acetyl histone H3K9/K14, anti-α-tubulin, or swine anti-ASFV serum). HRP-conjugated secondary antibodies were used, and proteins were detected via chemiluminescence. [2]
- Immunofluorescence: Vero cells grown on coverslips were treated with 4-Phenylbutyric acid and infected (MOI=0.1). At 24 and 48 hpi, cells were fixed with paraformaldehyde in HPEM buffer, permeabilized with PBS/Triton X-100, blocked, and incubated with FITC-conjugated swine anti-ASFV serum. Nuclei and viral factories were visualized with DAPI-containing mounting medium. Images were acquired using an epifluorescence microscope. [2]
- Osteoclast differentiation and TRAP staining: Bone marrow-derived macrophages (BMMs) from C57BL/6J mice were incubated with M-CSF and RANKL for 40h to generate pre-osteoclasts. These were then treated with M-CSF and LPS (50 ng/ml) with or without 4-Phenylbutyric acid (0.5-1 mM) for 48h. Cells were fixed in formalin and stained for tartrate-resistant acid phosphatase (TRAP). TRAP-positive multinucleated cells (MNCs) with ≥3 nuclei were counted as osteoclasts. Area, maximum diameter, and fusion index (average nuclei per OC) were measured. [3]
- Autophagy detection (LC3II and p62 Western blot): Pre-osteoclasts were stimulated with LPS (50 ng/ml) for 24-48h with or without 4-Phenylbutyric acid (1 mM). Bafilomycin A1 (30 nM) was added 4h before harvest as a control. Whole-cell lysates were immunoblotted for LC3 and p62, with β-actin as loading control. 4-Phenylbutyric acid reduced LC3II accumulation and restored p62 levels. [3]
- Acidic vesicular organelle (AVO) quantification by flow cytometry: Cells were stained with acridine orange (1 μg/ml) for 20 min, washed, and analyzed on a flow cytometer. AVOs (autophagosomes/autolysosomes) appear bright red. 4-Phenylbutyric acid reduced the percentage of AVO-containing cells from 61.6% to 53.1% after LPS stimulation. [3]
- siRNA transfection: Pre-osteoclasts were transfected with 50 nM siRNA against ATG7 or scrambled siRNA using lipofectamine 3000 in Opti-MEM. After transfection, cells were incubated with LPS and M-CSF. Silencing was confirmed by RT-PCR and qPCR. ATG7 knockdown abolished the inhibitory effects of 4-Phenylbutyric acid on OC area and fusion. [3]

Female 10-week-old C57BL/6J mice were housed in the pathogen-free animal facility of IRC. All mice were handled in accordance with the guidelines of the Institutional Animal Care and Use Committee (IACUC) of the Immunomodulation Research Center (IRC), University of Ulsan. All animal procedures were approved by the IACUC of IRC. The approval ID for this study is # UOU-2014-014. Animals were randomized into the following 4 groups: vehicle control (n = 5), vehicle + 4-PBA (n = 6), LPS (n = 6), and LPS + 4-PBA (n = 6). Mice were treated with LPS in 200 μL phosphate-buffered saline (PBS) (or with PBS as a vehicle) once a week (5mg/kg, i.p.) for 3 weeks as described [19]. 4-PBA solution was prepared by titrating equimolecular amounts of 4-PBA and sodium hydroxide to reach pH 7.4; mice were injected daily intraperitoneally in 200 μL PBS (or with PBS as a vehicle) at a dose of 240 mg/kg for 3 weeks. Mice were sacrificed by CO2 asphyxiation. To determine the bone mineral density (BMD) and microarchitecture of the long bone, the right femur was scanned in a high-resolution Micro CT (μCT) SkyScan 1176 System. Scans were performed with an effective detector pixel size of 6.9 μm and a threshold of 77–255 mg/cc. Trabecular bone was analyzed in a region 1.6 mm in length and located 0.1 mm below the distal femur growth plate. A total of 75–125 tomographic slices were acquired; 3 D analyses were performed with CT volume software. The structural parameters such as bone volume fraction (BV/TV), trabecular thickness (Tb. Th), and trabecular space (Tb. Sp.) were analyzed. In vivo markers of bone resorption were measured according to the manufacturer’s directions; serum collagen-type I fragments (CTX-1) were assessed using a RatLaps EIA assay. Serum osteocalcin was assessed using an osteocalcin EIA kit, and alkaline phosphatase (ALP) was quantitated using a colorimetric kinetic determination kit. Serum MCP-1 was quantitated by sandwich ELISA using the recommended Abs according to manufacturer’s instruction[3].

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LPS-induced bone loss model: Female C57BL/6J mice (10-week-old) were randomized into four groups (n=5-6 per group). Mice received intraperitoneal (i.p.) injections of LPS (5 mg/kg in 200 μl PBS) once a week for 3 weeks to induce bone loss. 4-Phenylbutyric acid was prepared by titrating equimolar amounts of 4-PBA and sodium hydroxide to pH 7.4, and administered daily via i.p. injection at 240 mg/kg in 200 μl PBS for 3 weeks. Control mice received PBS vehicle. At the end of treatment (13 weeks old), mice were sacrificed by CO2 asphyxiation. Femurs were collected for micro-CT analysis and TRAP staining. Serum was collected for CTX-1, ALP, osteocalcin, and MCP-1 measurement. A dose-response study was performed at 120, 240, and 500 mg/kg; 240 mg/kg showed maximal protection. [3]

Absorption, Distribution and Excretion
Under fasting conditions, after a single oral dose of 5 g sodium chlorate, the peak plasma concentration (Cmax) is 195-218 µg/mL, and the time to peak concentration (Tmax) is 1 hour. The effect of food on drug absorption is unclear. Approximately 80-100% of the dose is excreted via the kidneys within 24 hours as the conjugate phenylacetylglutamine. It is estimated that each 1 g of sodium chlorate ingested produces 0.12-0.15 g of phenylacetylglutamine nitrogen. Metabolism/Metabolites The main sites of metabolism for sodium chlorate are the liver and kidneys. Chlorobutyric acid is rapidly metabolized to phenylacetic acid via β-oxidation. Phenylacetic acid conjugates with phenylacetyl-CoA, which in turn conjugates with glutamine via acetylation to form phenylacetylglutamine.

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Biological Half-Life
After a single oral dose of 5 g sodium chlorate, the elimination half-life of chlorate is 0.76 to 0.77 hours.

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When 4-Phenylbutyric acid was administered as a 7-day continuous intravenous infusion at 400 mg/kg/day to patients with refractory solid tumors, the mean steady-state plasma concentrations were: 446 μM for 4-PBA, 1464 μM for its metabolite phenylacetic acid, and 1217 μM for phenylacetylglutamine. No unidentified metabolites were detected. [3]

Hepatotoxicity
Although urea cycle disorders are caused by a deficiency of liver enzymes responsible for nitrogen removal, patients typically present with hyperammonemia without other characteristic or biochemical evidence of liver injury. Therefore, serum transaminase, alkaline phosphatase, and bilirubin levels are usually normal or only slightly elevated. Neonates with hyperammonemia may present with hepatomegaly, but other non-urea cycle-related liver functions and liver histology are normal. Chlorobutyrate can help acutely lower ammonia levels and maintain them within the normal or near-normal range, but usually does not affect other liver functions. In open-label studies, a small number of patients (particularly those with ornithine carbamoyltransferase [OTC] deficiency) have experienced elevated ALT or AST, but these are usually attributed to the primary disease or its complications. Chlorobutyrate has not been associated with cases of clinically significant liver injury with jaundice. Probability Score: E (Unlikely a cause of clinically significant liver injury, but its use is limited).

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Protein Binding
When used in combination with tauroursodeoxycholic acid as a compound preparation, the in vitro plasma protein binding rate of phenylbutyric acid is 82%.

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4-Phenylbutyric acid did not show any detrimental effect on the viability of BMMs under the assayed conditions (MTT assay). [3]
- In Vero E6 cells, 4-Phenylbutyric acid at 5 mM was non-cytotoxic as determined by trypan blue exclusion assay over 72 hours. [2]
- In a Phase I clinical study of 4-Phenylbutyric acid administered as a continuous intravenous infusion at 410 mg/kg/day in patients with refractory solid tumors, the drug was reported as safe and tolerated. The primary toxicity was neurocortical and was reversible after drug discontinuation. [3]
- In another Phase I study with oral administration, the recommended dose for 4-Phenylbutyric acid in refractory solid tumors was 27 g/day. [3]

[1]. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin Cancer Res. 2002 Apr;8(4):1206-12.

[2]. Sodium phenylbutyrate abrogates African swine fever virus replication by disrupting the virus-induced hypoacetylation status of histone H3K9/K14. Virus Res. 2017 Oct 15;242:24-29.

[3]. 4-Phenylbutyric acid protects against lipopolysaccharide-induced bone loss by modulating autophagy in osteoclasts. Biochem Pharmacol. 2018 May;151:9-17.

4-Phenylacetic acid (PPA) is a monocarboxylic acid with a butyric acid ester replaced by a phenyl group at the C-4 position. It is a histone deacetylase inhibitor with anticancer activity. It inhibits the proliferation, invasion, and migration of glioma cells and induces apoptosis. Furthermore, it inhibits protein isopreneization, reduces plasma glutamine levels, increases fetal hemoglobin production through transcriptional activation of the γ-globin gene, and affects hPPARγ activation. It functions as an EC 3.5.1.98 (histone deacetylase) inhibitor, antitumor drug, apoptosis inducer, and prodrug. Functionally, it is related to butyric acid and is the conjugate acid of 4-phenylbutyrate ester. PPA is a fatty acid, a derivative of butyric acid, naturally produced by the fermentation of colonic bacteria. It exhibits various cellular and biological effects, such as alleviating inflammation and acting as a chemochaete. It is used to treat inherited metabolic syndromes, neuropathy, and urea cycle disorders. PPA is a nitrogen binder. Its mechanism of action is as an ammonium ion binder. Sodium chlorate and sodium benzoate are orphan drugs approved for the treatment of hyperammonemia in patients with urea cycle disorders, a group of diseases involving deficiencies in at least eight rare inherited enzymes. The urea cycle is the primary pathway for clearing excess nitrogen, including ammonia, and the absence of any urea cycle enzyme typically leads to elevated serum ammonia levels, which can be serious, life-threatening, and result in permanent neurological damage and cognitive impairment. Both sodium chlorate and sodium benzoate act by promoting alternative nitrogen clearance pathways. Neither sodium chlorate nor sodium benzoate has been associated with cases of liver injury, either during treatment with elevated serum enzymes or with clinically apparent acute liver injury. 4-Phenylenic acid has been reported in Streptomyces, and relevant data are available. See also: Sodium chlorate (active ingredient); Chlorobutyrate (active ingredient). Drug Indications Chlorobutyrate is used to treat a variety of conditions, including urea cycle disorders, neonatal-onset deficiencies, and late-onset deficiencies in patients with a history of hyperammonemic encephalopathy. Phthalate must be used in conjunction with restricted dietary protein intake, and in some cases, essential amino acid supplementation is also necessary. Phthalate (in the form of sodium phenylbutyrate) is used in combination with tauroursodeoxycholic acid to treat adult amyotrophic lateral sclerosis (ALS). Mechanism of Action Sodium phenylbutyrate is the most commonly used salt in phenylbutyrate formulations. It is a prodrug that is rapidly metabolized to phenylacetic acid. Phenylacetic acid binds to phenylacetyl-CoA, which then binds to glutamine via acetylation to form phenylacetylglutamine. Phenylacetylglutamine is subsequently excreted by the kidneys, thus providing an alternative mechanism for the excretion of waste nitrogen from the urea cycle. Like urea, each molecule of phenylacetylglutamine contains two moles of nitrogen. Pharmacodynamics Phthalate reduces elevated plasma glutamine levels in patients with urea cycle disorders. It increases the excretion of waste nitrogen in the form of phenylacetylglutamine. In the gut, chlorhexidine has been shown to reduce mucosal inflammation, regulate transepithelial fluid transport, and improve oxidative state. Some studies have reported the antitumor properties of chlorhexidine, indicating that it can promote growth arrest and apoptosis in cancer cells. Research also suggests that chlorhexidine can function as an ammonia scavenger, a chemochaete, and an inhibitor of histone deacetylases.

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African swine fever virus (ASFV) is a highly lethal swine pathogen with no vaccine or treatment. 4-Phenylbutyric acid (sodium phenylbutyrate) fully abrogated ASFV replication in vitro, which was associated with disrupting the virus-induced hypoacetylation of histone H3K9/K14, promoting an open chromatin state possibly enabling expression of host genes detrimental to infection. [2]
- 4-Phenylbutyric acid has been clinically used to treat urea cycle disorders and is known as an inhibitor of endoplasmic reticulum (ER) stress and histone deacetylases (HDACs). This study shows its novel role in protecting against inflammatory bone loss by inhibiting autophagy in osteoclasts via NF-κB. [3]
- The synergistic antiviral effect between 4-Phenylbutyric acid and enrofloxacin (an ASFV-topoisomerase II poison) suggests a potential combination therapy for ASFV. This synergism may be due to HDACi-promoted histone hyperacetylation enhancing topoisomerase II poison access to DNA. [2]

C10H12O2

164.2

164.083

C, 73.15; H, 7.37; O, 19.49

1821-12-1

Sodium 4-phenylbutyrate;1716-12-7;4-Phenylbutyric acid-d11;358730-86-6;4-Phenylbutyric acid-d5;64138-52-9;4-Phenylbutyric acid-d2;461391-24-2

4775

White to off-white solid powder

1.1±0.1 g/cm3

290.7±9.0 °C at 760 mmHg

49-52ºC

187.9±13.9 °C

0.0±0.6 mmHg at 25°C

1.535

2.42

1

2

4

12

137

0

O([H])C(C([H])([H])C([H])([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O

OBKXEAXTFZPCHS-UHFFFAOYSA-N

nChI=1S/C10H12O2/c11-10(12)8-4-7-9-5-2-1-3-6-9/h1-3,5-6H,4,7-8H2,(H,11,12)

4-Phenylbutyric acid

4-Phenylbutyric acid; AI3 12065; 4-PHENYLBUTYRIC ACID; 4-Phenylbutanoic acid; 1821-12-1; Benzenebutanoic acid; Benzenebutyric acid; Phenylbutyrate; Phenylbutyric acid; gamma-Phenylbutyric acid; AI312065; AI3-12065

2934.99.03.00

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)

DMSO : ~100 mg/mL (~609.01 mM)
H2O : ~2 mg/mL (~12.18 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (15.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (15.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (15.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 33.33 mg/mL (202.98 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)