phenylbutyrates

Summary

Summary: Derivatives of 4-phenylbutyric acid, including its salts and esters.

Top Publications

  1. Kulp S, Chen C, Wang D, Chen C, Chen C. Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer. Clin Cancer Res. 2006;12:5199-206 pubmed
  2. Lee B, Rhead W, Diaz G, Scharschmidt B, Mian A, Shchelochkov O, et al. Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control. Mol Genet Metab. 2010;100:221-8 pubmed publisher
    ..Urinary PAGN, which is stoichiometrically related to nitrogen scavenging, may be a useful biomarker for both dose selection and adjustment for optimal control of venous ammonia. ..
  3. Kubota K, Niinuma Y, Kaneko M, Okuma Y, Sugai M, Omura T, et al. Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. J Neurochem. 2006;97:1259-68 pubmed
    ..These results suggest that 4-PBA suppresses ER stress by directly reducing the amount of misfolded protein, including Pael-R accumulated in the ER. ..
  4. Wiley J, Meabon J, Frankowski H, Smith E, Schecterson L, Bothwell M, et al. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells. PLoS ONE. 2010;5:e9135 pubmed publisher
    ..Pharmaceutical agents, such as PBA, that stimulate alpha/gamma-cleavage of APP by modifying intracellular trafficking should be explored as AD therapeutics. ..
  5. Cai Z, Li F, Gong W, Liu W, Duan Q, Chen C, et al. Endoplasmic reticulum stress participates in aortic valve calcification in hypercholesterolemic animals. Arterioscler Thromb Vasc Biol. 2013;33:2345-54 pubmed publisher
    ..These data provide novel evidence that ER stress participates in AV calcification development, and suggest that ER stress may be a novel target for AV calcification prevention and treatment. ..
  6. Del Signore S, Amante D, Kim J, Stack E, Goodrich S, Cormier K, et al. Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotroph Lateral Scler. 2009;10:85-94 pubmed publisher
    ..These data suggest that NaPB may not interfere with the pharmacologic action of riluzole in ALS patients. ..
  7. Srinivasan K, Sharma S. Sodium phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation. Behav Brain Res. 2011;225:110-6 pubmed publisher
    ..It also suggest that targeting ER stress might offer a promising therapeutic approach and benefits against ischemic stroke associated with comorbid type 2 diabetes. ..
  8. Schultz J, Ibrahim S, Vera J, Kunz M. 14-3-3sigma gene silencing during melanoma progression and its role in cell cycle control and cellular senescence. Mol Cancer. 2009;8:53 pubmed publisher
  9. van der Velden L, Stapelbroek J, Krieger E, van den Berghe P, Berger R, Verhulst P, et al. Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. Hepatology. 2010;51:286-96 pubmed publisher
    ..We propose that treatment with pharmacological chaperones may represent an effective therapeutic strategy to ameliorate the recurrent attacks of cholestasis in patients with intermittent (BRIC1) disease. ..
  10. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith R, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313:1137-40 pubmed
    ..Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes. ..

Detail Information

Publications81

  1. Kulp S, Chen C, Wang D, Chen C, Chen C. Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer. Clin Cancer Res. 2006;12:5199-206 pubmed
  2. Lee B, Rhead W, Diaz G, Scharschmidt B, Mian A, Shchelochkov O, et al. Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control. Mol Genet Metab. 2010;100:221-8 pubmed publisher
    ..Urinary PAGN, which is stoichiometrically related to nitrogen scavenging, may be a useful biomarker for both dose selection and adjustment for optimal control of venous ammonia. ..
  3. Kubota K, Niinuma Y, Kaneko M, Okuma Y, Sugai M, Omura T, et al. Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. J Neurochem. 2006;97:1259-68 pubmed
    ..These results suggest that 4-PBA suppresses ER stress by directly reducing the amount of misfolded protein, including Pael-R accumulated in the ER. ..
  4. Wiley J, Meabon J, Frankowski H, Smith E, Schecterson L, Bothwell M, et al. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells. PLoS ONE. 2010;5:e9135 pubmed publisher
    ..Pharmaceutical agents, such as PBA, that stimulate alpha/gamma-cleavage of APP by modifying intracellular trafficking should be explored as AD therapeutics. ..
  5. Cai Z, Li F, Gong W, Liu W, Duan Q, Chen C, et al. Endoplasmic reticulum stress participates in aortic valve calcification in hypercholesterolemic animals. Arterioscler Thromb Vasc Biol. 2013;33:2345-54 pubmed publisher
    ..These data provide novel evidence that ER stress participates in AV calcification development, and suggest that ER stress may be a novel target for AV calcification prevention and treatment. ..
  6. Del Signore S, Amante D, Kim J, Stack E, Goodrich S, Cormier K, et al. Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotroph Lateral Scler. 2009;10:85-94 pubmed publisher
    ..These data suggest that NaPB may not interfere with the pharmacologic action of riluzole in ALS patients. ..
  7. Srinivasan K, Sharma S. Sodium phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation. Behav Brain Res. 2011;225:110-6 pubmed publisher
    ..It also suggest that targeting ER stress might offer a promising therapeutic approach and benefits against ischemic stroke associated with comorbid type 2 diabetes. ..
  8. Schultz J, Ibrahim S, Vera J, Kunz M. 14-3-3sigma gene silencing during melanoma progression and its role in cell cycle control and cellular senescence. Mol Cancer. 2009;8:53 pubmed publisher
  9. van der Velden L, Stapelbroek J, Krieger E, van den Berghe P, Berger R, Verhulst P, et al. Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. Hepatology. 2010;51:286-96 pubmed publisher
    ..We propose that treatment with pharmacological chaperones may represent an effective therapeutic strategy to ameliorate the recurrent attacks of cholestasis in patients with intermittent (BRIC1) disease. ..
  10. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith R, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313:1137-40 pubmed
    ..Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes. ..
  11. Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman Gomez J, et al. Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 2009;125:2737-43 pubmed publisher
    ..In summary, our results aid in the understanding of miRNA gene regulation showing that aberrant DNA methylation and histone modifications work together to induce silencing of miRNAs in CRC. ..
  12. de Almeida S, Picarote G, Fleming J, Carmo Fonseca M, Azevedo J, de Sousa M. Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation. J Biol Chem. 2007;282:27905-12 pubmed
    ..Together, these data shed light on the molecular mechanisms involved in HFE C282Y-related HH and open new perspectives on the use of orally active chemical chaperones as a therapeutic approach for HH. ..
  13. Ryningen A, Stapnes C, Bruserud Ø. Clonogenic acute myelogenous leukemia cells are heterogeneous with regard to regulation of differentiation and effect of epigenetic pharmacological targeting. Leuk Res. 2007;31:1303-13 pubmed
  14. Ozcan L, Ergin A, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9:35-51 pubmed publisher
    ..Taken together, our results may provide the basis for a novel treatment of obesity...
  15. Ammerpohl O, Thormeyer D, Khan Z, Appelskog I, Gojkovic Z, Almqvist P, et al. HDACi phenylbutyrate increases bystander killing of HSV-tk transfected glioma cells. Biochem Biophys Res Commun. 2004;324:8-14 pubmed
  16. Steinmann J, Halldorsson S, Agerberth B, Gudmundsson G. Phenylbutyrate induces antimicrobial peptide expression. Antimicrob Agents Chemother. 2009;53:5127-33 pubmed publisher
    ..Our findings contribute to understanding of the regulation of AMP expression and suggest that PBA and/or ST7 is a promising drug candidate for treatment of microbial infections by strengthening the epithelial antimicrobial barriers. ..
  17. Savickiene J, Treigyte G, Magnusson K, Navakauskiene R. Response of retinoic acid-resistant KG1 cells to combination of retinoic acid with diverse histone deacetylase inhibitors. Ann N Y Acad Sci. 2009;1171:321-33 pubmed publisher
    ..The results indicate the possibility of using the combination of agents for therapeutic strategy in RA-resistant acute myeloid leukemia to produce both differentiation and apoptosis. ..
  18. Hogarth P, Lovrecic L, Krainc D. Sodium phenylbutyrate in Huntington's disease: a dose-finding study. Mov Disord. 2007;22:1962-4 pubmed
    ..We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. ..
  19. Tveten K, Holla Ø, Ranheim T, Berge K, Leren T, Kulseth M. 4-Phenylbutyrate restores the functionality of a misfolded mutant low-density lipoprotein receptor. FEBS J. 2007;274:1881-93 pubmed
    ..These data suggest that rescue of mutant low-density lipoprotein receptor is possible and that it might be feasible to develop pharmacologic chaperones to treat familial hypercholesterolemia patients with class 2 mutations. ..
  20. Lu Q, Wang D, Chen C, Hu Y, Chen C. Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem. 2005;48:5530-5 pubmed
    ..S)-11 at concentrations as low as 0.1 microM was effective in causing histone hyperacetylation and p21(WAF/CIP1) overexpression and suppressing proliferation in cancer cells. ..
  21. Smith W, Diaz G, Lichter Konecki U, Berry S, Harding C, McCandless S, et al. Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate. J Pediatr. 2013;162:1228-34, 1234.e1 pubmed publisher
    ..To examine ammonia levels, pharmacokinetics, and safety of glycerol phenylbutyrate (GPB; also referred to as HPN-100) and sodium phenylbutyrate (NaPBA) in young children with urea cycle disorders (UCDs)...
  22. Daosukho C, Chen Y, Noel T, Sompol P, Nithipongvanitch R, Velez J, et al. Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury. Free Radic Biol Med. 2007;42:1818-25 pubmed
    ..Thus, combining HDACIs with ADR could add a new mechanism to fight cancer while simultaneously decrease ADR-induced cardiotoxicity. ..
  23. Camacho L, Olson J, Tong W, Young C, Spriggs D, Malkin M. Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors. Invest New Drugs. 2007;25:131-8 pubmed
    ..Future studies evaluating PBA's ability to induce histone acetylation and cell differentiation alone or in combination with other anti-neoplastics are recommended. ..
  24. Hauswald S, Duque Afonso J, Wagner M, Schertl F, Lubbert M, Peschel C, et al. Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clin Cancer Res. 2009;15:3705-15 pubmed publisher
    ..To investigate whether additional drug transporters are regulated by HDACi and how this affects cytotoxicity, acute myeloid leukemia (AML) cells were examined...
  25. Ono K, Ikemoto M, Kawarabayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, et al. A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human alpha-synuclein A30P + A53T transgenic mice. Parkinsonism Relat Disord. 2009;15:649-54 pubmed publisher
    ..These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders. ..
  26. Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas H, et al. Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease. Proc Natl Acad Sci U S A. 2005;102:11023-8 pubmed
    ..These alterations in mRNA expression correlate with disease progression and response to experimental treatment. Such markers may provide clues to the state of HD and may be of predictive value in clinical trials. ..
  27. Kisseberth W, Murahari S, London C, Kulp S, Chen C. Evaluation of the effects of histone deacetylase inhibitors on cells from canine cancer cell lines. Am J Vet Res. 2008;69:938-45 pubmed publisher
    ..Micromolar concentrations of HDAC inhibitors OSU-HDAC42 and SAHA induced histone acetylation, cytotoxicity, and apoptosis in canine cancer cells. In general, OSU-HDAC42 was more potent than SAHA. ..
  28. Powell P, Bellanne Chantelot C, Flanagan S, Ellard S, Rooman R, Hussain K, et al. In vitro recovery of ATP-sensitive potassium channels in ?-cells from patients with congenital hyperinsulinism of infancy. Diabetes. 2011;60:1223-8 pubmed publisher
  29. Jeng Y, Lin N, Chang P, Huang Y, Pang V, Liu C, et al. Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model. Exp Eye Res. 2007;84:486-92 pubmed
    ..Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction. ..
  30. Qi W, Mu J, Luo Z, Zeng W, Guo Y, Pang Q, et al. Attenuation of diabetic nephropathy in diabetes rats induced by streptozotocin by regulating the endoplasmic reticulum stress inflammatory response. Metabolism. 2011;60:594-603 pubmed publisher
    ..In conclusion, 4-PBA exerts a marked renoprotective effect possibly due to modulating ER stress and related inflammatory cascade. ..
  31. Zhang S, Suvannasankha A, Crean C, White V, Chen C, Farag S. The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells. Int J Cancer. 2011;129:204-13 pubmed publisher
    ..In conclusion, AR-42 has potent cytotoxicity against MM cells mainly through gp130/STAT-3 pathway. The results provide rationale for clinical investigation of AR-42 in MM. ..
  32. Tang C, Koulajian K, Schuiki I, Zhang L, Desai T, Ivovic A, et al. Glucose-induced beta cell dysfunction in vivo in rats: link between oxidative stress and endoplasmic reticulum stress. Diabetologia. 2012;55:1366-79 pubmed publisher
  33. Diaz G, Krivitzky L, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013;57:2171-9 pubmed publisher
  34. Prulière Escabasse V, Planes C, Escudier E, Fanen P, Coste A, Clerici C. Modulation of epithelial sodium channel trafficking and function by sodium 4-phenylbutyrate in human nasal epithelial cells. J Biol Chem. 2007;282:34048-57 pubmed
  35. Ebbel E, Leymarie N, Schiavo S, Sharma S, Gevorkian S, Hersch S, et al. Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry. Anal Biochem. 2010;399:152-61 pubmed publisher
    ..Thus, this approach contributes to understanding metabolic pathways that differ among HD patients being treated with SPB. ..
  36. Hayashi H, Sugiyama Y. Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11). Mol Pharmacol. 2009;75:143-50 pubmed publisher
    ..Modulation of short-chain ubiquitination can regulate the change in the degradation rate of cell-surface-resident BSEP by 4PBA treatment and PFIC2-type mutations...
  37. Lea M, Sura M, desBordes C. Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR) gamma agonists and antagonists. Anticancer Res. 2004;24:2765-71 pubmed
    ..We conclude that potential PPAR gamma antagonists may fail to reverse the growth inhibitory effect of PPAR gamma ligands and may themselves act as growth inhibitory agents. ..
  38. Gray S, Al Sarraf N, Baird A, Cathcart M, McGovern E, O Byrne K. Regulation of EP receptors in non-small cell lung cancer by epigenetic modifications. Eur J Cancer. 2009;45:3087-97 pubmed publisher
    ..Epigenetic regulation of the EPs may be central to the precise role COX-2 may play in the evolution of individual tumours. ..
  39. Li J, Wang J, Yu Q, Wang M, Zhang S. Endoplasmic reticulum stress is implicated in retinal inflammation and diabetic retinopathy. FEBS Lett. 2009;583:1521-7 pubmed publisher
    ..These findings indicate that ER stress is a potential mediator of retinal inflammation in diabetic retinopathy. ..
  40. Sorrenson B, Suetani R, Williams M, Bickley V, George P, Jones G, et al. Functional rescue of mutant ABCA1 proteins by sodium 4-phenylbutyrate. J Lipid Res. 2013;54:55-62 pubmed publisher
    ..These results suggest 4-PBA may warrant further investigation as a potential therapy for increasing cholesterol efflux and HDL-C levels. ..
  41. Phuphanich S, Baker S, Grossman S, Carson K, Gilbert M, Fisher J, et al. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study. Neuro Oncol. 2005;7:177-82 pubmed
    ..The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. ..
  42. Lucas D, Alinari L, West D, Davis M, Edwards R, Johnson A, et al. The novel deacetylase inhibitor AR-42 demonstrates pre-clinical activity in B-cell malignancies in vitro and in vivo. PLoS ONE. 2010;5:e10941 pubmed publisher
    ..Together, these data demonstrate that AR-42 has in vitro and in vivo efficacy at tolerable doses. These results strongly support upcoming phase I testing of AR-42 in B-cell malignancies. ..
  43. Taylor M, Banerjee T, Navarro Garcia F, Huerta J, Massey S, Burlingame M, et al. A therapeutic chemical chaperone inhibits cholera intoxication and unfolding/translocation of the cholera toxin A1 subunit. PLoS ONE. 2011;6:e18825 pubmed publisher
    ..PBA is currently used as a therapeutic agent to treat urea cycle disorders. Our data suggest PBA could also be used in a new application to prevent or possibly treat cholera. ..
  44. Petri S, Kiaei M, Kipiani K, Chen J, Calingasan N, Crow J, et al. Additive neuroprotective effects of a histone deacetylase inhibitor and a catalytic antioxidant in a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. 2006;22:40-9 pubmed
  45. Hattori Y, Fukushima M, Maitani Y. Non-viral delivery of the connexin 43 gene with histone deacetylase inhibitor to human nasopharyngeal tumor cells enhances gene expression and inhibits in vivo tumor growth. Int J Oncol. 2007;30:1427-39 pubmed
    ..Thus, the amplified Cx43 expression by an antitumor agent, an HDAC inhibitor, may have great potential as a growth inhibitor for nasopharyngeal tumors. ..
  46. Yam G, Gaplovska Kysela K, Zuber C, Roth J. Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis. Invest Ophthalmol Vis Sci. 2007;48:1683-90 pubmed
    ..These data point to the possibility of a chemical chaperone treatment for myocilin-caused primary open-angle glaucoma. ..
  47. Lichter Konecki U, Diaz G, Merritt J, Feigenbaum A, Jomphe C, Marier J, et al. Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate. Mol Genet Metab. 2011;103:323-9 pubmed publisher
  48. Phillips J, Griffin B. Pilot study of sodium phenylbutyrate as adjuvant in cyclophosphamide-resistant endemic Burkitt's lymphoma. Trans R Soc Trop Med Hyg. 2007;101:1265-9 pubmed
    ..Findings suggested that for this effect PB pre-treatment should be given for a week before CPM treatment. A larger study is indicated. ..
  49. Sarker P, Ahmed S, Tiash S, Rekha R, Stromberg R, Andersson J, et al. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy. PLoS ONE. 2011;6:e20637 pubmed publisher
    ..Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in dysentery. ..
  50. Mizukami T, Orihashi K, Herlambang B, Takahashi S, Hamaishi M, Okada K, et al. Sodium 4-phenylbutyrate protects against spinal cord ischemia by inhibition of endoplasmic reticulum stress. J Vasc Surg. 2010;52:1580-6 pubmed publisher
    ..Reduction in ER stress-induced spinal cord injury was achieved by the administration of 4-PBA. 4-PBA may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury. ..
  51. Zode G, Kuehn M, Nishimura D, Searby C, Mohan K, Grozdanic S, et al. Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma. J Clin Invest. 2011;121:3542-53 pubmed publisher
    ..These results demonstrate that ER stress is linked to the pathogenesis of POAG and may be a target for treatment in human patients. ..
  52. Lopez C, Feng F, Herman J, Nyati M, Lawrence T, Ljungman M. Phenylbutyrate sensitizes human glioblastoma cells lacking wild-type p53 function to ionizing radiation. Int J Radiat Oncol Biol Phys. 2007;69:214-20 pubmed
    ..This suggests the potential application of combined PB and radiotherapy in glioblastoma harboring mutant p53. ..
  53. Ryu H, Smith K, Camelo S, Carreras I, Lee J, Iglesias A, et al. Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J Neurochem. 2005;93:1087-98 pubmed
    ..Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS. ..
  54. Vilatoba M, Eckstein C, Bilbao G, Smyth C, Jenkins S, Thompson J, et al. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis. Surgery. 2005;138:342-51 pubmed
    ..Reduction in ER stress-induced hepatocellular injury was achieved by the administration of PBA. Targeting the ER-associated cell death pathway might offer a novel approach to reduce I/R injury to the liver. ..
  55. Dromparis P, Paulin R, Stenson T, Haromy A, Sutendra G, Michelakis E. Attenuating endoplasmic reticulum stress as a novel therapeutic strategy in pulmonary hypertension. Circulation. 2013;127:115-25 pubmed publisher
    ..Attenuating ER stress with clinically used chemical chaperones may be a novel therapeutic strategy in pulmonary hypertension with high translational potential. ..
  56. van den Berghe P, Stapelbroek J, Krieger E, de Bie P, van de Graaf S, de Groot R, et al. Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin. Hepatology. 2009;50:1783-95 pubmed publisher
    ..These findings might enable novel treatment strategies in WD by directly enhancing the protein expression of mutant ATP7B with residual copper export activity. 1795.). ..
  57. Ricobaraza A, Cuadrado Tejedor M, Marco S, Pérez Otaño I, Garcia Osta A. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus. 2012;22:1040-50 pubmed publisher
  58. Basseri S, Lhotak S, Sharma A, Austin R. The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response. J Lipid Res. 2009;50:2486-501 pubmed publisher
    ..Taken together, these results suggest that UPR activation contributes to adipogenesis and that blocking its activation with 4-PBA prevents adipocyte differentiation and weight gain in mice. ..
  59. Burkitt K, Ljungman M. Phenylbutyrate interferes with the Fanconi anemia and BRCA pathway and sensitizes head and neck cancer cells to cisplatin. Mol Cancer. 2008;7:24 pubmed publisher
  60. Rahman S, Qadri I, Janssen R, Friedman J. Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis. J Lipid Res. 2009;50:2193-202 pubmed publisher
  61. Hayashi H, Sugiyama Y. 4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps. Hepatology. 2007;45:1506-16 pubmed
    ..Moreover, treatment of Sprague-Dawley rats with 4PBA resulted in an increase in BSEP expression at the canalicular membrane, which was accompanied by an increase in the biliary excretion of [(3)H]taurocholic acid (TC)...
  62. Lam P, Pearson C, Soroka C, Xu S, Mennone A, Boyer J. Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. Am J Physiol Cell Physiol. 2007;293:C1709-16 pubmed
  63. Ozcan U, Ozcan L, Yilmaz E, Düvel K, Sahin M, Manning B, et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell. 2008;29:541-51 pubmed publisher
    ..These results demonstrate ER stress as a critical component of the pathologies associated with dysregulated mTOR activity and offer the possibility to exploit this mechanism for new therapeutic opportunities. ..
  64. Xiao C, Giacca A, Lewis G. Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and beta-cell dysfunction in humans. Diabetes. 2011;60:918-24 pubmed publisher
    ..These results suggest that PBA may provide benefits in humans by ameliorating the insulin resistance and ?-cell dysfunction induced by prolonged elevation of free fatty acids. ..
  65. Bueno M, Perez de Castro I, Gómez de Cedrón M, Santos J, Calin G, Cigudosa J, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13:496-506 pubmed publisher
    ..Thus, miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies. ..
  66. Bonapace G, Waheed A, Shah G, Sly W. Chemical chaperones protect from effects of apoptosis-inducing mutation in carbonic anhydrase IV identified in retinitis pigmentosa 17. Proc Natl Acad Sci U S A. 2004;101:12300-5 pubmed
    ..These experiments suggest a promising approach to treatment of RP17 that might delay the onset or possibly prevent this autosomal dominant form of RP. ..
  67. Ammerpohl O, Trauzold A, Schniewind B, Griep U, Pilarsky C, Grutzmann R, et al. Complementary effects of HDAC inhibitor 4-PB on gap junction communication and cellular export mechanisms support restoration of chemosensitivity of PDAC cells. Br J Cancer. 2007;96:73-81 pubmed
  68. Merzvinskyte R, Treigyte G, Savickiene J, Magnusson K, Navakauskiene R. Effects of histone deacetylase inhibitors, sodium phenyl butyrate and vitamin B3, in combination with retinoic acid on granulocytic differentiation of human promyelocytic leukemia HL-60 cells. Ann N Y Acad Sci. 2006;1091:356-67 pubmed
    ..Our results suggest that the use of two HDACI altogether before the induction of differentiation and acting via chromatin remodeling may be promising for the treatment of acute promyelocytic leukemia. ..
  69. Singh O, Vij N, Mogayzel P, Jozwik C, Pollard H, Zeitlin P. Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cells. J Proteome Res. 2006;5:562-71 pubmed
    ..Subsets of these proteins were confirmed by immunoblot analysis. These data represent a first-draft of the pharmacoproteomics map of 4-PBA treated cystic fibrosis bronchial epithelial cells. ..
  70. Sargeant A, Rengel R, Kulp S, Klein R, Clinton S, Wang Y, et al. OSU-HDAC42, a histone deacetylase inhibitor, blocks prostate tumor progression in the transgenic adenocarcinoma of the mouse prostate model. Cancer Res. 2008;68:3999-4009 pubmed publisher
    ..These results suggest that OSU-HDAC42 has value in prostate cancer prevention. [Cancer Res 2008;68(10):3999-4009]. ..
  71. Hanada S, Harada M, Kumemura H, Bishr Omary M, Koga H, Kawaguchi T, et al. Oxidative stress induces the endoplasmic reticulum stress and facilitates inclusion formation in cultured cells. J Hepatol. 2007;47:93-102 pubmed
    ..The oxidative stress coupled with limited inhibition of the proteasome induces dysfunction of the ER and results in inclusion formation in cultured cells. This suggests that ER stress plays a role in MB formation in liver disease. ..
  72. Mimori S, Okuma Y, Kaneko M, Kawada K, Hosoi T, Ozawa K, et al. Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress. Biol Pharm Bull. 2012;35:84-90 pubmed
    ..These results suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases. ..
  73. Cudkowicz M, Andres P, Macdonald S, Bedlack R, Choudry R, Brown R, et al. Phase 2 study of sodium phenylbutyrate in ALS. Amyotroph Lateral Scler. 2009;10:99-106 pubmed publisher
    ..While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels. ..
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