Sodium Phenylbutyrate

Please review the following sodium phenylbutyrate studies showing the depth of research that has taken place since the 1980s.

Brose RD, Shin G, McGuinness MC, Schneidereith T, Purvis S, Dong GX, Keefer J, Spencer F, Smith KD. Activation o the stress proteome as a mechanism for small molecule therapeutics. Hum Mol Genet Oct 2012 1;21(19):4237-52.


Baarine M, Ragot K, Genin EC, Hajj HE, Trompier D, Andreoletti P, Ghandour MS, Menetrier F, Cherkaoui-Malki M, Savary S, Lizard. Peroxisomal and mitochondrial status of two murine oligodendrocytic cell lines (158N,158JP): potential models or the study of peroxisomal disorders associated with dysmyelination processes. J Neurochem Oct 2009;111(1):119-31


Gondcaille C., Depreter M. Fourcade S., Lecca M.R., Leclercq S., Martin P.G.P., Pineau T., Cadepond F., ElEtr M., Bertrand N., Beley A., Duclos S., De Craemer D., Roels F., Savary S., Bugaut M., Phenylbutyrate up-regulates the adrenoleucodystrophy-related gene as a nonclassical peroxisome proliferator.  The Journal of Cell Biology, Vol. 169, No. 1, 93-104, April 2005.


Girard S, Bruckert E, Turpin G. Endocrine disease in adrenoleukodystrophy. Ann Med Intern (Paris) Feb 2001;152(1):15-26.


McGuinness MC, Zhang HP, Smith KD Evaluation of pharmacological induction of fatty acid beta-oxidation in X-linked adrenoleukodystrophy. Mol Genet Metab Sept-Oct 2001;74(1-2):256-63



Wei H., Kemp S, McGuinness MC, Moser AB, Smith KD.  Pharmacological induction of Peroxisomes in Peroxisome Biogenesis Disorders.  Ann Neurol, 47:286-296.  2000.

Wagner, G. Towards a life prolonging pill? Small molecules with anti-ageing properties. Current Drug Targets 2006: 7 (11): 1531-1537


Burzynski, S.R. Aging:gene silencing or gene activation? Med Hypotheses 2005: 64 (1): 201-208

Kang H-L., Benzer S., Min K-T. Life extension in Drosophila by feeding a drug.  PNAS Jan 22, 2002, Vol. 99 No. 2, (838-843).

owards a life prolonging pill? Small molecules with anti-ageing properties. Current Drug Targets 2006: 7 (11): 1531-1537

Romieu P, Host L, Gobaille S, Sandner G, Aunis D, Zwiller J. Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats. J Neurosci 2008; 28 (38): 9342-9348

Barbero-Camps E, Fernandez A, Baulies A, Martinez L, Fernandez-Checa J, Colell A. Endoplasmic reticulum stress mediates amyloid ß neurotoxicity via mitochondrial cholesterol trafficking. Am J Pathol July 2014;184(7):2066-81

Corbet, G., Roy A., Pahan K. Sodium Phenylbutyrate Enhances Astrocytic Neurotrophin Synthesis via Protein Kinase C (PKC)-mediated Activation of cAMP-esponse Element-binding Protein (CREB) Implications for Alzheimer Disease Therapy. The American Society for Biochemistry and Molecular Biology 2013



Cuadrado-Tejefor, M., Ricobaraza A., Torrijo R., Franco R., Garcia-Osta, A., Phenylbutyrate is a
Multifaceted Drug that Exerts Neuroprotective Effects and Reverses the Alzheimer’s Disease-like Phenotype of a Commonly Used Mouse Model. Current Pharmaceutical Design, Vol.19, No. 28, pp. 5076-5084(9). November 28, 2013

Ricobaraza A., Cuadrado-Tejefor M., Marco S., Perez-Otano I., Garcia-Osta A. Phenylbutyrate rescues
dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease.
Hippocampus.2012 May: 22(5):1040-50.doi: 10.1002/hipo.20883.Epub 2010 Nov 10.

Cuadrado-Tejedor M, Garcia-Osta A, Ricobaraza A, Oyarzabal J, Franco R. Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer’s disease. Curr Med Chem 2011;18(36):5545-53.

Ricobaraza, A., Cuadrado-Tejedor, M., Pérez-Mediavilla, A., Frechilla, D., Del Río, J., García-
Osta, A. Phenylbutyrate Ameliorates Cognitive Deficit and Reduces Tau Pathology in an Alzheimer’s disease Mouse Model. Neuropsychopharmacology January 14, 2009;doi:10.1038/nnp.2008.229

Liu N, Qiang W, Kuang X, Thuillier P, Lynn WS, Wong Paul KY. The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidation cell death. J Neurovirol Aug 2002;8(4):318-25

Corman A, Jung B, Häggblad, Bräutigam, Lafarga V, Lindemalm L, Hühn, Carreras-Puigvert J, Fernandez-Capetillo O. A Chemical Screen Identifies Compounds Limiting the Toxicity of C9ORF72 Dipeptide Repeats. Cell Chem Biol. Feb 2019;26(2):235-243.e5.


Del Signore, S.J., Amante, D.J., Kim, J., Stack, E.C., Goodrich, S., Cormier, K., Smith, K., Cudkowicz, M.E., Ferrante, R.J. Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotrophic Lateral Sclerosis, Volume 10,, Issue 2, April 2009.


Cudkowicz, M.E., Aneres, P.L., et al. Macdonald, S.A., et al. Phase 2 study of sodium Phenylbutyrate in ALS. Amyotroph Lateral Scler. 2009; 10(2):99-106


Scott, S, Kranz, JE, Cole, J, Lincecum, JM, Thompson, K, Kelly, N, Bostrom, A, Theodoss, J, Al-Nakhala, BM, Vieira FG, Ramasubbu, J, Heywood, JA. Design, power and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 2008; 9 (1): 4-15.



Cudkowicz, ME, Andres, PL, Choudry, R, MacDonald, SA, Zhang, H, Schoenfeld, D, Ferrante, RJ. Safety and dose escalating study of oral sodium phenylbutyrate in subjects with ALS Neurology 2007; 68 (12, Suppl. 1): A90.


Traynor BJ, Bruijn L, O’Neill F, Fagan G, Cudkowicz ME. Neuroprotective agents for clinical trials in ALS: a systematic assessment. Neurology 2006; 67(1):20-27


Petri S., Kiaei M., Kipiani K., Chen J., Calingasan N.Y., Crow J.P., Beal M.F., Additive neuroprotective effects of a histone deacetylase inhibitor and a catalytic antioxidant in a transgenic mouse model of amyotrophic lateral sclerosis.  Neurobiology of Disease 22, 40-49 (2006).


Carri, MT, Grignaschi, G, Bendotti, C. Targets in ALS: designing multidrug therapies. Trends Pharmacol Sci 2006; 27 (5): 267-273.



Traynor, BJ, Bruijn, L, Conwit, R, Beal, F, O’Neill, G, Fagan, SC, Cudkowicz, ME. Neurology 2006; 67 (1): 20-27.


Bruijn LI, Cudkowizc, M. Therapeutic targets for amyotrophic lateral sclerosis: Current treatments and prospects for more effective therapies. Expert Rev Neurother 2006: 6 (3): 417-428.


DiBernardo, A.B., Cudkowicz, M.E. Translating preclinical insights into effective human trials in ALS.  Biochimica et Biophysica Acta 1762 (2006) 1139-1149.


Ryu H, Smith K, Camelo S.I., Carreras I., Lee J., Iglesias A.H., Dangond F., Cormier K.A., Cudkowicz M.E., Brown Jr. R.H., Ferrante R.J.  Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. Journal of Neurochemistry, 2005, 93, 1087-1098.

Almeida, A., Murakami, Y., Baker, A., Maeda, Y., Roberts, I., Kinoshita, T., Layton, DM, Karadimitria, A.  Targeted Therapy for Inherited GPI Deficiency.  The New England Journal of Medicine 2007; 356:1641-7


Tveten K, Holla OL, Ranheim T, Berge KE, Leren TP, Kulseth MA. 4-Phenylbutyrate restores the functionality of a misfolded mutant low-density lipoprotein receptor. FEBS J 2007;274(8):1881-1893.


TvetenK, Holla OL, Renheim T, Berge KE, Leren TP, Kulseth MA. Rescue of the low density lipoprotein receptor 2A mutant G544V by 4-Phenylbutyrate.  Molecular chaperones and the heat shock response 2006;187.

Lee Sy, Hong EH, Jeong JY, Cho J, Seo JH, K HJ, Cho HJ. Esterase-sensitive cleavable histone deacetylase inhibitor-coupled hyaluronic acid nanoparticles for boosting anticancer activities against lung adenocarcinoma. Biomater Sci Nov 2019;7(11):4624-4635

Tanaka T, Kojima K, Yokota K, Tanaka Y, Ooizumi Y, Ishii S, Nishizawa, Yokoi K, Ushiku H, Kikuchi M, Kojo K, Minatani N, Katoh H, Sato T, Nakamura T, Sawanobori, Watanabe M, Yamashita K. Comprehensive Genetic Search to Clarify the Molecular Mechanism of Drug Resistance Identifies ASCL2-LEF1/TSPAN8 Axis in Colorectal Cancer. Ann Surg Oncol May 2019;26(5):1401-1411

Qian K, Sun L, Zhou G, Ge H, Meng Y, Li J, Li X, Fang X. Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo. Cancer Biother Radiopharm May 2018;33(4):139-145

Al-Keilani MS, Alzoubi KH, Jaradat SA. The effect of combined treatment with sodium phenylbutyrate and cisplatin, erlotinib or gefitinib on resistant NSCLC cells. Clin Pharmacol Oct 2018;10:135-140

Jin X, Wu N, Dai J, Li Q, Xiao X. TXNIP mediates the differential responses of A549 cells to sodium butyrate and sodium 4-phenylbutyrate treatment. Cancer Med Feb 2017;6(2):424-438

Xu YW, Xheng SB, Chen BS, Wen Y, Zhu SW. Effect of sodium phenylbutyrate on the sensitivity of PC3/DTX-resistant prostate cancer cells to docetaxel. Nan Fang Yi Ke Da Xue Xue Bao Nov 2017;37(1):130-134

Xu, X., Zheng, S., Chen, B., Wen, Y., Zhu, S. sodium Phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration. Onco Targets & Therapy, May 12, 2016, 9: 2825-2833

Kikuchi, M., Yamashita, K., Waraya, N., Ushiku, H., Kojo, K., Ema, A., Kosaka, Y., Katoh, H., Sengoku, N., Enomoto, T., Tanino, H., Sawanobori, M., Watanabe. Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer. Oncotarget, 7(2): 1741-1753 January 2016

Shi S, Tan P, Yan B, Gao R, Zhao J, Wang J, Gup J, Li N, Ma Z. ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells. Oncol Rep May 2016;35(5):2606-14

Fadeev NP, Kharisov RI, Kovan’ko EG, Pustovalov YI. Study o Antitumor Activity of Sodium Phenylbutyrate, Histon Deacetylase Inhibitor on Ehrlich Carcinoma Model. Bull Exp Biol Med Sep 2015;159(5):652-4

Welsch, L., Welsch, T., Dovzhanskiy, I., Felix, K., Giese, N.A., Krysko, D. Impact of the histone deacetylase inhibitor 4-phenylbutyrate on the clearance of apoptotic pancreatic carcinoma cells by human macrophages. International Journal of Oncology, 2012, 40(2). P. 427-435

Chen WQ, Feng FL, Gu HB, et al. Effect of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and surviving genes. Zhonghua Kou Qiang Yi Xue Za Zhi, July 2010; 45(7):416-20

De-shum, Pan, Wei-qiang, Chen. The effects of sodium phenylbutyrate (SPB) on the expression of p21 and survivine genes on human tongue squamous cancer cell line Tca8113. Chinese Pharmacological Bulletin, February 2010

Steinmann, J., Halldórsson, S., Agerberth, B., Gudmundsson, G.H. Phenylbutyrate Induces Antimicrobial Peptide Expression. Antimicrobial Agents and Chemotherapy, Page. 5127-5133, Vol. 53, December 2009

Holm, E; Schade, I. Effects of short-chain and saturated long-chain fatty acids on tumor growth-in vitro and experimental in vivo effects. Aktuelle Ernahrungsmedizin 2008;33(5):225-230.

Cortez, CC; Jones, PA. Chromatin,cancer and drug therapies. Mutat Res-Fundam Mol Mech Mutagen 2008;647(1-2):44-51.

Murahari, S; Jalkanen, AL; Kulp, SK; Chen, C-S; Jubala, CM; Fosmire, SP; Modiano, JF; Fossey, SL; London, CA, Kisseberth, WC.OSU-HDAC42, a novel histone deacetylase inhibitor with potent antitumor effects on human and canine osteosarcoma cells. Proceedings of the American Association for Cancer Research Annual Meeting 2008;49:578.

Wang, C., Meng, M., Zhang, J., Jin, C., Jiang, J., Ren, H., Jiang, J., Qin, C., and Yu, D. Chinese Medical Journal 2008; 121(17):1707-1711.

Burkitt, Kyunghee and Ljungman, Mats. Phenylbutyrate interferes with the Fanconi anemia and BRCA pathway and sensitizes head and neck cancer cells to cisplatin. Molecular Cancer 7:24, March 2008.

Svechnikova, Irina, Almqvist, Per M., Ekström, Tomas J. HDAC inhibitors effectively induce cell type-specific differentiation in human glioblastoma cell lines of different origin. International Journal of Oncology 32:821-827, 2008

Huynh, L; Grant, J; Leroux, JC; Delmas, P; Allen, C. Prediction the solubility of the anti-cancer agent docetaxel in small molecule excipients using computational methods. Pharm Res 2008; 25:147-157.

Hurtubise, A; Bernstein, ML; Momparler, RL. Preclinical evaluation of the antineoplastic action of 5-aza-2’-deoxycytidine and different histone deacetlylase inhibitors on human Ewing’s sarcoma cells. Cancer Cell Int 2008;8:16.


Koutsourea, Al; Fousteris, MA; Arsenou, ES; Papageorgiou, A; Pairas, GN; Nikolaropoulos, SS. Rational design, synthesis and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters. Bioorg Med Chem 2008; 16(9):5207-5215.

Estey, E. New drugs in acute myeloid leukemia. Seminars in Oncology 2008;35(4):439-448.

Picard, V; Bergeron, A.; Larue, H; Fradet, Y. MAGE-A9 mRNA and protein expression in bladder cancer. Int J Cancer 2007; 120 (10):2170-2177.

Vila-Carriles, WH; Zhou, Z-H; Bubien, JK; Fuller, CM; Benos, DJ. Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells. J Biol Chem 2007;282(47):34381-34391.

Entin-Meer, M; Rephaeli, A; Yang, X; Nudelman, A; Haas-Kogan, DA. AN-113, a novel prodrug of 4-phenylbutyrate with increased anti-neoplastic activity in glioma cell lines. Cancer Lett 2007; 253(2):205-214.

Christov, Konstantin, Grubbs, Clinton J; Shilkaitis, Anne, Juliana, M Margaret; Lubet, Ronald A. Short-term modulation of cell proliferation and apoptosis and preventive/therapeutic efficacy of various agents in a mammary cancer model. Clin Cancer Res 2007; 13(18 Part. 1):5488-5496.

Christov, K; Grubbs, C; Juliana, M; Luber, R. Correlation of the preventive/therapeutic efficacy of agents in the methylnitrosourea (MNU) mammary cancer model with changes in cell proliferation and apoptosis following short-term treatment. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:997.

Sung, MW; Waxman, S. Combination of cytotoxic-differentiation therapy with 5-fluorourcail and phenylbutyrate in patients with advanced colorectal cancer. Anticancer Res 2007;27(2):995-1001.

Caraway, HE; Gore, SD. Addition of histone deacetylase inhibitors in combination therapy. J. Clin Oncol 2007; 25(15):1955-1956.

Verheul, HMW; Qian, DZ; Carducci, MA; Pili, R. Sequence-dependent antitumor effects of differentiation agents in combination with cell cycle-dependent cytotoxic drugs. Cancer Chemother Pharmacol 2007; 60(3):329-339.

Ammerpohl, O; Trauzold, A; Schniewind, B; Griep, U; Pilarsky, C; Grutzmann, R; Saeger, H-D; Janssen, O; sipos, B; Kloppel, G; Kalthoff, H. 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(1):73-81.

Jiemjit, A; Fandy, TE; Baylin, SB; Carraway, H; Herman, JG; Gore, SD. Sequential administration of DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) induces apoptosis with caspase and reactive oxygen species (ROS)-dependent synergy. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:249.

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(6):1427-1439.


Lyon, CM; Klinge, D; Liechty, KC; Grimes, MJ; Grimes, J; Thomas, C; March, T; Stidley, C; Keith, R; Belinsky, SA. Rosiglitazone prevents the progression of pre-invasive lung cancer in a murine model. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:395.

Cunha De Santis , G; de barros Tamarozzi, M; Sousa, RB; Moreno, Se; Secco, D; Garcia, AB; Lima, ASG; Faccioli, LH; Falcoao, RP; Cunha, FQ; Rego, EM. Adhesion molecules and Differentiation Syndrome: phenotypic and functional analysis of the effect of ATRA, As203, phenylbutyrate, and G-CSF in acute promyelocytic leukemia. Haematologica 2007; 92(12):1615-1622.

Meng, M; Wang, C-T; Jiang, J-M; Zhang, J-C; Jiang, J-J; Jin, C-J. Expression of histone deacetylase 4 in human liver carcinoma cell line Bel-7402 and its significance. Chinese Journal of Cancer Biotherapy Chin. J. cancer Biother 2007; 14(2):153-157.

Lu, Y-S; Kashida, Y; Kulp, SK; wang, Y-C; Wang, D; Hung, J-H; Tang, M; Lin, Z-Z; Chen, T-J; Cheng, A-L; Chen, C-S. Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellualr carcinoma. Hepayology 2007; 46(4):1119-1130.

Svechnikova, I; Ammerpohl, O; Ekstroem, TJ. P21waf1/Cip1 partially mediates apoptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun 2007; 354(2):466-471.

Lu, Y-S; Kashida, Y; Jung, J-H; Chen, C-S; Wang, Y-C; Cheng, A-L; Chen, C-S. In vivo efficacy of OSH-HDAC42, a novel phenylbutyrate-based histone deacetylase inhibitor, in human hepatocellular carcinoma animal models. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:169.

Lubbert, M; Claus, R. Epigenetic inactivation of gene expression. New therapeutic targets in hematology. Onkologe 2007;13(1):46-55. [email protected] or [email protected].

Claus, R; Router, B, Loubbert, M. Targets of epigenetics therapy-Gene reactivation as a novel approach in MDS treatment. Cancer Treat Rec 2007; 33(Suppl. 1):S47-S52.

Luebbert, M. Which myelodysplastic syndromes patients are candidates for treatment with decitabine. Leukemia Research 2007; 31(Suppl. 1):S20.

Gore, SD. Do histone deacetylase inhibitors have a place in the treatment of myelodysplastic syndromes? Leukemia Research 2007; 31(Suppl. 1):S21.

Phillips, JA; Griffin, BE. Pilot study of sodium phenylbutyrate as adjuvant in cyclophosphamide-resistant endemic Burkitt’s lymphoma. Trans R Soc Trop Med Hyg 2007; 101(12):1265-1269.

Milkevitch, M; Jeitner, TM; Beardsley, NJ; Delikatny, EJ. Lovastatin enhances phenylbutyrate-induced MR-visible glycerophosphocholine but not apoptosis in DU145 prostate cells. Biochim Biophys Acta 2007; 1771(9):1166-1176.

Phillips John A., Griffin, Beverly E. Pilot study of sodium Phenylbutyrate as adjuvant in cyclophosphamide-resistant endemic Burkitt’s lymphoma. Royal Socity of Tropical Medicine and Hygiene doi: 10.1016/j.trstmh.2007.06.0200.

Lopez, CA, Feng, FY, Herman, JM, Nyati, MK, Lawrence,TS, Ljungman, M. Phenylbutyrate Sensitizes Human Glioblastoma Cells Lacking Wild-Type P53 Function To Ionizing Radiation. Int. J. Radiation Oncology Biol. Phys, Vol. 69, No. 1, PP. 214-220, 2007.

L.H. Camacho, J. Olson, W.P. Tong, .W. Young, D.R. Spriggs, M.G. Malkin. Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors. Invest. New Drugs, 2007 25:131-138.

Vila-Carriles, WH; Kovacs, GG; Bubien, JK; Gillespie GY; Fuller, CM; Benos, DJ. Cellular localization of acid sensing ion channels in human astrocytes and gliomas. FASEB Journal 2006; 20(4, Part1):A325.

Christov, K; Grubbs, C; Lubet, R; Altered cell proliferation and apoptosis as biomarkers for identifying preventive/therapeutic agents against chemically induced mammary cancers. Breast Cancer Research and Treatment 2006; 100(Suppl. 1):S58.

Lea, MA; Ibeh, C; Shah, N; Moyer, MP. Enhanced differentiation of colon cancer cells induced by combinations of inhibitors of kinases and of historic deacetylases. Proceedings of the American Association for Cancer Research Annual Meeting 2006; 47:1184.

Gore, SD;, Jiemjit, A; Silverman, LB; Aucott, T; Baylin, S; Carraway, H; Douses, T; Fandy, T; Herman, J; Karp, JE; Licht, JD.; Murgo, AJ.; Odchimar-Reissig, R; Smith, BD; Zwiebel, JA.; Sugar, E. Cimbined methyltransferase/Histone deacetylase inhibition with 5Azacitidine and MS-275 in patients with MDS, CMMoL and AML: Clinical response, Histone Acetylation and DNA damage. Blood 2006; 108(11, part 1):156A-157A.

Sun, J; Liu, S; Yu, J; Wei, M; Mao, C; Ding, H; Kearney, J; Huynh, L; Paschka, P; Wang, D; Klisovic, RB; Perrotti, D; Chen, C-S; Blum, WG; Marcucci, G. Characterization of HDACI OSU42 as a novel histone deacetylase inhibitor in AML cell lines. Blood 2006; 108(11 Part 1):563A.

Gore, SD; Baylin, S; Sugar, E; Carraway, H; Miller, CB; Carducci, M; Grever, M; Galm, O; Dauses, T; Karp, JE; Rudek, MA; Zhao, M; Smith, BD; Manning, J; Jiemjit, A; Dover, G; Mays, A; Zwiebel, J; Murgo, A; Weng, L-J; Herman, JG. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006; 66(12):6361-6369.

Brock, MV. Clinical aspects of molecular biology for the diagnosis and treatment of esophageal cancer. Esophagus 2006; 3(3):91-94.

Beyer, SJ; Kulp, SK; Baird, M; Auer, H; Kornacker, K; Chen, C-S; Beer, DG; Kresty, LA. The effects of a phenylbutyrate-drived histone deacetylase inhibitor (HDAC-42) on acid-induced gene expression patterns of SEG-1 human esophageal adenocarcinoma cells. Proceedings of the American Association for Cancer Research Annual Meeting 2006; 47:1128-1129.

West, DA; Lucas, DM; Davis, ME; De lay, MD; Johnson, AJ; Guster, SE; Freitas, MA; Parthun, MR; Wang, D; Kulp, SK; Grever, MR; Chen, C-S; Byrd, JC. The novel histone deacetylase inhibitor OSU-HDAC42 has class I and II histone deacetylase (HDAC) inhibitory activity and represents a novel therapy for chronic lymphocytic leukemia. Blood 2006; 108(11 Part 1): 794A-795A.

Lyon, CM; Klinge, D; Liechty, KC; Belinsky, SA. DNA demethylating agents and a PPA-gamma agonist cooperate to induce apoptosis in lung cancer cell lines. Proceedings of the American Association for Cancer Research Annual Meeting 2006; 47:10.

Meletis, J; Viniou, N; Terpos, E. Novel agents for the management of myelodysplastic syndromes. Med Sci Monit 2006; 12(9):RA 194-RA206.

Kulp, SK; Chen, C-S; Wang, D-S; Chen, C-Y; Chen, C-S. Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer. Clin Cancer Res 2006; 12(17):5199-5206.

Wanda H. Vila-Carriles, Gergely Gy Kovacs, Biljana Jovov, Zhen-Hong Zhou, Amit K. Pahwa, Garrett Colby, Ogenna Esimai, G. Yancey Gillespie, Timothy B. Mapstone, James M. Markert, Catherine M. Fuller, James K. Bubien, Dale J. Benos. Surface Expression of ASIC2 Inhibits the Amiloride-sensitive Current and Migration of Glioma Cells. The Journal of Biological Chemistry VOL. 281, NO> 28, pp. 19220 – 19232, July 14, 2006.

Mack, GS. Epigenetic cancer therapy makes headway. Journal of the National Cancer Institute 2006;98(20):1443-1444.

Fouladi, M. Histone deacetylase inhibitors in cancer therapy. Cancer Investigation 2006;24(5):521-527.

Galm, O; Herman, JG; Bbaylin, SB. The fundamental role of epigenetics in hematopoietic malignancies. Blood Rev 2006;20(1):1-13.

P. Malask, S. Chanel, L.H. Camacho, S. Soignet, P.O. Dandolfi, I. Guernah, R. Warrell, S. Nimer. Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome. Leukemia 2006, 20, 212-217.

Schniewind B., Heintz K., Kurdow R., Ammerpohl O., Trauzold A., Emme D., Dohrmann P., Kalthoff H. Combination Phenylbutyrate/gemcitabine therapy effectively inhibits in vitro and in vivo growth of NSCLC by intrinsic apoptotic pathways. Journal of Carcinogenesis 2006,1477-3163-5-25.

Jin C., Park J.W., Choi J.W., Kang H., Jin G.B., Choi S.M., Park S.S., Ryu D., Jang L.C. Antiproliferative Effect of Phenylbutyrate in AsPC-1 Pancreatic Cancer Cell Line. Korean J. Hepatobiliary Pancreat Surg. 2006 Mar: 10(1):1-9. Korean

Kouraklis G., Theocharis S. Histone deacetylase inhibitors: A novel target of anticancer therapy (Review). Oncology Reports 15: 489-494, 2006.

Sampathkumar S-g, Jones MB, Meledeo MA, Hida K, Sheh T, Gomatputra P, Yarema KJ. Carbohydrate-based small molecules as anti-cancer drugs: Short chain fatty acid-hexosamine hybrids. Glycobiology 2005; 15 (11): 1249-1250.

Lu Q, Wang D-S, Chenm C-S, Hu Y-D, Chen C-S. Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem 2005; 48 (17): 5530-5535.

Gao, J; X-y; Xu F-I; Liu D-y; Lei D-p. Effects of sodium phenylbutyrate alone or in combination with fluorouracil or cisplatin on laryngeal carcinoma Hep-2 cell line. Zhongguo Xinyao yu Linchuang Zazhi 2005; 24(10):778-781.

Gao, J; Ruan, X; Pan, X; Xu, F; Lei, D; Liu, D. The effect of sodium phenylbutyrate to agents used in induction chemotherapy on laryngeal carcinoma cells Hep-2 in vitro. Lin Chuang Er Bi Yan Hou Ke Za Zhi 2005; 19(15):680-682.

Luebbert, M. Combined targeting of the epigenetic silence in leukemia: Cooperating activities of DNA methylation and histone deacetylation inhibitors. Leukemia Research 2005; 29(7):727-728.

Wang, H-E; Wu, H-C; Kao, S-J; Tseng, F-W; Wang, Y-S; Yu, H-M; Chou, S-L; Yen, S-H; Chi, K-H. Modulation of 5-fluorouracil cytotoxicity through thymidylate synthase and NF-kappaB down-regulation and its application on the radiolabelled iododeoxyuridine therapy on human hepatoma cell. Biochem Pharmacol 2005; 69(4):617-626.

Milkevitch, M; Shim, H; Pilatus, U; Pickup, S; Wehrle, JP; Samid, D; Poptani, H; Glickson, JD; Delikatny, EJ. Increases in NMR-visible lipid and glycerophosphocholine during phenylbutyrate-induced apoptosis in human prostate cancer cells. Biochim Biophys Acta 2005; 1734(1):1-12.

Rudek MA, Zhao M, He P, Hartkle C, Gilbert J, Gore SD,. Carducci MA, Baker SD. Pharmacokinetics of 5-Azacitidine Administered With Phenylbutyrate in Patients With Refractory Solid Tumors or Hematologic Malignancies. Journal of Clinical Oncology Vol 23 #17 June 10, 2005.

Belinsky S.A., Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer. Carcinogenesis Vol. 26, No. 9 (1481-1487) 2005.

Mortazavi, A.; Hoot, DR; Carlton, PS; Wang, S; Degroff, VL.; Lu, Q; Kulp, S; Chen, C-S; Clinton, SK. Inhibition of cell growth and induction of apoptosis in bladder cancer cell lines by a novel histone deacctylase inhibitor derived from phenylbutyrate. Proceedings of the American Association for Cancer Research Annual meeting 2005; 46(Supplement S): 422.

Hao, C-I; Tang, K-j; Chen, S, Xing, H-y; Wang, M; Wang, J-x. 5-Aza-2’-deoxycytidine enhances differentiation and apoptosis induced by phenylbutyrate in Kasumi-1 cells. Zhonghua Zhong Liu Za Zhi 2005;27(3):148-151.

Meng M., Jiang J.M., Liu H., In C.Y., Zhu J.R. Effects of sodium phenylbutyrate on differentiation and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cells lines. Chinese Journal of Digestive Diseases 2005; 6; 189-192.

Garcia-Manero, G; Issa, J-P. Histone deacetylase inhibitors: A review of their clinical status as antineoplastic agents. Cancer Investigation 2005;23(7):635-642.

Phuphanich S, Baker SD, Grossman SA, Carson KA, Gilbert MR, Fisher JD, Carducci MA. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study. Neuro-Oncology Vol 7 pg 177-182, April 2005.

Munshi A, Kurland JF, Nishikawa T, Tanaka T, Hobbs Ml, Tucker SL, Ismail S, Stevens C, Meyn RE. Histone deacetylase inhibitors raidosensitize human melanoma cell by suppressing DNA repair activity. Clin Cancer Res 2005; 11 (13): 4912-4922.

Siitonen, T., Koistinen, P., Savolainen, E. Increase in Ara-C cytotoxicity in the presence of valproate, a histone deacetylase inhibitor, is associated with the concurrent expression of cyclin D1 and p27Kip1 in acute myeloblastic leukemia cells. Leukemia Research 29 (2004) 1335-1342.

Liu M., Brusilow W.S.A., Needleman R., Activity of the yeast Tat2p tryptophan permease is sensitive to the anti-tumor agent 4-phenylbutyrate. Curr Genet 46:256-268 (2004).

Emionite L., Galmozzi F., Grattarola M., Boccardo F., Vergani L, Toma S., Histone Deacetylase Inhibitors Enhance Retinoid Response in Human Breast Cancer Cell Lines. Anticancer Research 24: 4019-4024 (2004).

Zhang X., Wei L., Yang Y., Yu Q. Sodium 4-Phenylbutyrate Induces Apoptosis of Human Lung Carcinoma Cells Through Activating JNK Pathway. Journal of Cellular Biochemistry 93:819-829 (2004).

Sachs M.D., Ramamurthy M., van der Poel H., Wickham T.J., Lamfers M., Gerritsen W., Chowdhury W., Li Y., Schoenberg M.P., Rodriguez R. Histone deacetylase inhibitors upregulate expression of the coxsackie adenovirus receptor (CAR) preferentially in bladder cancer cells. Cancer Gene Therapy (2004) 11, 477-486.

Kim, Y.H., Park, J.W., Lee, J.Y., et al. Sodium Phenylbutyrate sensitizes TRAIL-mediated apoptosis by induction of transcription from the DR5 gene promoter through Ap1 sites in colon Cancer cells. Carcinogenesis. 2001;25:1813-20

Nakagawa H., Intrathecal or intracavitary administration of sodium butyrate to treat neoplastic meningitis and malignant glioma Proceedings of the AACR, Vol. 45:5241, March 2004.

X.-N. Li, S. Parikh, Q. Shu, H.-L. Jung, C.-W. Chow, L. Perlaky, H.-C. E. Leung, J. Su, S. Blaney, and C. C. Lau Phenylbutyrate and Phenylacetate Induce Differentiation and Inhibit Proliferation of Human Medulloblastoma Cells Clin. Cancer Res., February 1, 2004; 10(3): 1150 – 1159.

Burzynski, SR, Lewy, RI, Weaver, R, Janicki, T, Jurida, G, Khan, M, Larisma, CB, Paszkowiak, J, , Szymkowski, B. Long-Term Survival and Complete Response of a Patient With Recurrent Diffuse Intrinsic Brain Ctem Glioblastoma Multiforme. Integrative Cancer Therapies, 3(3); 2004 pp. 257-261.

Appelskog I.B., Ammerpohl O., Svechnikova I.G., Lui W-O., Almqvist P.M., Ekström T.J. Histone deacetylase inhibitor 4-phenylbutyrate suppresses GAPDH mRNA expression in glioma cells. International Journal of Oncology 24:1419-1425, 2004.

Linz, Uta, Complete response of a recurrent, multicentric malignant glioma in a patient treated with Phenylbutyrate. Journal of Neuro-Oncology 66:251, 2004.

Asklune, T., Appelskog I.B., Ammerpohl O., Ekstron T.J., Almqvist, P.M. Histone deacetylase inhibitor 4-phenylbutyrate modulates glial fibrillary acidic protein and connexin 43 expression, and enhances gap-junction communication in human glioblastoma cells. European Journal of Cancer, 2004 Vol 40, No. 7.

Gray S.G., Quian C.-N., Furge K., Guo X., The B.T., Microarray profiling of the effects of histone deacetylase inhibitors on gene expression in cancer cell lines. Int. J of Onc. 24:773-795, 2004.

Chung, Yih-Lin, Wang, Ae-June, Yao, Lin-Fen, Antitumor Histone deacetylase inhibitors suppress cutaneous radiation syndrome: Implications for increasing therapeutic gain in cancer radiotherapy. Molecular Cancer Therapeutics 2004; 3(3):317-325

Belinsky S.A., Klinge D.M., Stidley C.A., Issa J-P., Herman J.G., March T.H., Baylin S.B., Inhibition of DNA Methylation and Histone Deacetylation Prevents Murine Lung Cancer. Cancer Research (63) 7089-7093, November 1, 2003.

Sun Li-Jun, Huang Qiang, Lan Qing, Du Zi-wei, Hu Geng-xi, Wang Ai-dong, Gene Expression Profiling of Phenylbutyrate Induced Differentiation of Glioma Cells by cDNA Array. Chinese Journal of Cancer Research 15(1):38-42, 2003.

Thompson P., Balis F., Baruti M., Berg S.S., Adamson P., Klenk R., Aiken A., Packer R., Murry D.J., Jakacki R., Blaney S.M. Pharmacokinetics of phenylacetate administered as a 30-min infusion in children with refractory cancer. Cancer Chemother Pharmacol (2003) 52:417-423.

Finzer P., Stöhr M., Seibert N., Rösl F., Phenylbutyrate inhibits growth of cervical carcinoma cells independent of HPV type and copy number J. Cancer Res. Clin. Oncol. (2003) 129:107-113.

Witt O, Mönkemeyer S, Rönndahl G, Erdlenbruch B, Reinhardt D, Kanbach K, and Pekrun A. Induction of fetal hemoglobin expression by the histone deacetylase inhibitor apicidin. Blood, Mar 2003; 101: 2001 – 2007.

Svechnikova I, Gray S.G, Kundrotiene J, Ponthan F, Kogner P, Ekström T. Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate. Int. Journal of Oncology 22: 579-588, 2003.

Gray S.G., Iglesias A.H., Teh B.T., Dangond F., Modulation of Splicing Events in Histone Deacetylase 3 by Various Extracellular and Signal Transduction Pathways Gene Expression, Vol. 11, pp. 13-21. Oct. 2002.

Baker M J, Brem S, Daniels S, Sherman B, Phuphanich S. Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate. J Neuro-Oncology; 59:239-242, 2002.

Boivin A-J., Momparler L.F., Hurtubise A., Momparler R.L.. Antineoplastic action of 5-aza-2’-deoxycytidine and phenylbutyrate on human lung carcinoma cells. Anti-Cancer Drugs. Vol 13 (869-874) 2002.

Dyer E.S., Paulsen M.T., Markwart S.M., Goh M., Livant D.L. and Ljungman M. Phenylbutyrate inhibits the invasive properties of prostate and breast cancer cell lines in the sea urchin embryo basement membrane invasion assay. Int. J. Cancer: 101, 496-499 (2002).

Shi M-G, Huang Q., Dong J, Sun Z-F., Lan Q. Experimental Study of Combination Therapy against Human Glioma Xenograft by Differentiation-Inducing Agent and Cytotoxic Chemotherapeutic Drug. Chinese Journal of Cancer, 2002, 21(10): 190-1094.

Du H-L., Qi Y., Shi Y-J., Bu D-F., Wu S-L. Apoptosis and Re-expression of p16 Gene in the Myeloma Cell Line U266 Induced by Synergy of Histone Deacetylase Inhibitor and Demethylating Agent. Chinese Journal of Cancer, 2002, 21(10):1057-1061.

Kennedy C., Byth K., Clarke C.L., DeFazio A., Cell Proliferation in the Normal Mouse Mammary Gland and Inhibition by Phenylbutyrate. Molecular Cancer Therapeutics Vol. 1, 1025-1033, Oct. 2002.

Sirchia S.M., Ren M., Pili R.ironi E., Somenzi G., Ghidoni R., Toma S., Nicolo G., Sacchi N.. Endogenous Reactivation of the RARß2 Tumor Suppressor Gene Epigenetically Silenced in Breast Cancer Cancer Research 62, 2455-2461, May 1, 2002.

Gore SD, Weng LJ, Zhai S, Figg WD, Donehower RC, Dover GJ, Grever M, Griffin CA, Grochow LB, Zabalena Y, Hawkins AL, Burks K and Miller CB. Impact of prolonged infusions of the Putative Differentiating Agent Sodium Phenylbutyrate on Myelodysplastic Syndromes and Acute Myeloid Leukemia. Clinical Cancer Research Vol. 8, 963-970, April 2002

Clarke K.O., Ludeman S.M., Springer J.B., Colvin O.M., Lea M.A., Harrison L.E. Exposure to a deuterated analogue of Phenylbutyrate retards S-phase progression in HT-29 colon cancer cells. Journal of Pharmaceutical Sciences, Vol. 91, No. 4, April 2002.

Chang T-H, Szabo E., Enhanced Growth Inhibition by Combination Differentiation Therapy with Ligands of Peroxisome Proliferator-activated Receptor-y and Inhibitors of Histone Deacetylase in Adenocarcinoma of the Lung. Clinical Cancer Research Vol. 8, 1206-1212, April 2002.

Shao N, Huang Q, Sun J, Dong J, Wang A, Wang F, Zhu W, A putative pathway in differentiation of SHG-44 glioma cells induced by sodium phenylbutyrate. The Human Genome Organization, HGM2002, Poster 451.

Zhu Q, Zhang J-W, Zhu H-Q, Shen Y-L, Flexor M, Jia P-M, Yu Y, Cai X, Waxman S, Lanotte M, Chen S-J, Chen Z, and Tong J-H. Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk. Blood, Feb 2002; 99: 1014 – 1022.

D-C Zhou, Kim SH, Ding W, Schultz C, Warrell R P, Jr, and Gallagher R E. Frequent mutations in the ligand-binding domain of PML-RAR after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-trans retinoic acid and histone deacetylase inhibitors in vitro and in vivo. Blood, Feb 2002; 99: 1356 – 1363.

Feinman R., Clarke, K.O., Harrison LE. Phenylbutyrate-Induced Apoptosis is Associated with Inactivation of Nf-кB in HT-29 colon cancer cells. Cancer Chemother Pharmacol (2002) 49:27-34.

Goh M., Chen F., Paulsen M.T., Yeager A.M., Dyer E.S., Ljungman M. Phenylbutyrate Attenuates the Expression of Bcl-XL, DNA-PK, Caveolin-1, and VEGF in Prostate Cancer Cells1. Neoplasia Vol. 3, No. 4, 2001, pp. 331-338.

Cosentini E, Haberl I, Pertschy P, Teleky B, Mallinger R, Baumgartner G, Wenzl E and Hamilton G. The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification. International Journal of Oncology 19: 1069-1074, 2001

Calvaruso G, Carabillo M, Guiliano M, Lauricella M, D’Anneo A, Vento R, Tesoriere G. Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: The effect of combined treatment with the topoisomerase I-inhibitor topotecan. Int. Journal of Oncology 18: 1233-1237, 2001.

Gilbert J, Baker SD, Bowling MK, Grochow L, Figg WD, Zabelina Y, Donehower RC, Carducci MA: A Phase I Dose Escalation and Bioavailability Study of Oral Sodium Phenylbutyrate in Patients with Refractory Solid Tumor Malignancies. Clin Cancer Res. 7: 2292-2300, 2001.

Gore SD, Weng LJ, Zhai S, Figg WD, Donehower RC, Dover GJ, Grever M, Griffin CA, Grochow LB, Rowinsky EK, Zabalena Y, Hawkins AL, Burks K, Miller CB: Impact of the Putative Differentiating Agent Sodium Phenylbutyrate on Myelodysplastic Syndromes and Acute Myeloid Leukemia. Clin Cancer Res. 7: 2330-9, 2001

Carducci MA, Gilbert J, Bowling MK, Noe D, Eisenberger MA, Sinibaldi V, Zabelina Y, Chen TL, Grochow LB, Donehower RC. A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-h infusion schedule. Clin Cancer Res. 7(10):3047-55, Oct 2001

Pili R, Kruszewski MP, Hager BW, Lantz J, Carducci MA. Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor growth and angiogenesis. Cancer Research 61, 1477-85, Feb. 15, 2001.

Berg S., Serabe B., Aleksic A., Bomgaars L., McGuffey L., Dauser R., Durfee J., Nuchtern J., Blaney S. Pharmacokinetics and cerebrospinal fluid penetration of phenylacetate and phenylbutyrate in the nonhuman primate. Cancer Chemother Pharmacol. 47: 385-390. February 2001.

Zhang Z, Zhao L, Zhou Y, Lu X, Wang Z, Wang J, Li W. Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress. Apoptosis May 2017;22(5):647-661


Takatori O, Usui S, Okajima M, Kaneko S, Ootsuji H, Takashima SI, Kobayashi D, Murai H, Furusho H, Takamura M. Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response. J Cardiovasc Pharmacol Ther May 2017;22(3):282-292


Jain K, Suryakumar G, Ganju L, Singh SB. Amelioration of ER stress by 4-phenylbutyric acid reduces chronic hypoxia induced cardiac damage and improves hypoxic tolerance through upregulation of HIF-1a. Vascul Pharmacol Aug 2016;83-36-46


Jian L, Lu Y, Lu S, Lu C. Chemical Chaperone 4-Phenylbutyric Acid Reduces Cardiac Ischemia/Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress. Med Sci Monit Dec 2016;22.5218-5227


Okajima, M., Takamura, M., Usui, S., Kaneko, S.  Sodium 4-phenylbutyrate protects against myocardial ischemia-reperfusion injury by reducing unfolded protein response-mediated apoptosis in mice. 30th International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium March 9-12, 2010


Daosukho,C., Chen, Y., Noel, T., Sompol, P., Nithipongvanitch, R., Velex, J.M., Oberley, T.D., St. Clair, D.K.  Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury.  Free Rauduc Bio Med. 42(12):1818-1825 June 15, 2007.

Lei J., Wang, B., Feng, D., Huang, L., Li, Y., Li, T., Zhu, G., Li, C., Li, F., Gao, G., Li, G. Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein. Frontiers Neurol., June 9, 2017.


Krishnamoorthy S, Sharma SS. 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 Nov 2011;225(1):110-6


Qi X., Hosoi T., Okuma Y., Kaneko M., Nomura Y., Sodium 4-Phenylbutyrate Protects against Cerebral Ischemic Injury, Molecular Pharmacology 66:899-908, 2004.

Suaud L, Mikker K, Panichelli AE, et al. 4-Phenylbutyrate stimulates Hsp 70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells. Journal Biol Chem 2011, Dec 30; 286(52):45083-92


Roque, T.,Boncoeur, E., Saint-Criq, V., Bonvin, E., Clement, A., Tabary, O., Jacquot, J.  Pro-inflammatory effect of sodium 4-phenylbutyrate in ΔF508-CFTR lung epithelial cells:  Involvement of ERK1/2 and JNK signaling.  JPET, June 23, 2008, DOI:10.1124/jpet.107.135186


Singh OV, Pollard HB, Zeitlin, PL. Chemical Rescue ofΔF508-CFTR Mimics Genetic Repair in Cystic Fibrosis Bronchial Epithelial Cells.  Molecular & Cellular Proteomics 7.5, February, 2008.


Virginie Prulièr-Escabasse, Carole Planés, Estelle Escudier, Pascale Fanen, André Coste, Christine Clerici.  Modulation of Epithelial Sodium Channel Trafficking and Function by Sodium 4-Phenylbutyrate in Human Nasal Epithelial Cells.  JBC Papers in Press, September 21, 2007, DOI 10.1074/jbc.M702384200.


Claudiu Iordache, Marek Duszyk. Sodium 4-Phenylbutyrate upregulates EnaC and sodium absorption in T84 cells. Experimental Cell Research 313 (2007) 305-311


Prulière-Escabasse, V., Planès, 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. Journal of Biological Chemistry September 2007


Vij, Neeraj, Fang, Shengyun and Zeitlin, Pamela L. Selective Inhibition of Endoplasmic Reticulum-associated Deradation Rescues ΔF508-Cystic Fibrosis Transmembrane Regulator and Suppresses Interleukin-8 Levels. The Journal of Biological Chemistry, Vol. 281, No. 25 pp. 17369-17378, June 23, 2006.


Singh O.V., Vij N., Mogayzel Jr. P.J.,  Jozwik C., Pollard H.B., Zeitlin P. L., Pharmacoproteomics of 4-Phenylbutyrate-treated IB3-1 Cystic Fibrosis Bronchial Epithelial Cells.  Journal of Proteome Research 2006, 5, 562-571.


Kerem E. Pharmacological Induction of CFTR Function in Patients with Cystic Fibrosis: Mutation-Specific Therapy. Pediatric Pulmonology 40:183-196 (2005).


Céline René, Magali Taulan, Florence Iral, Julien Doudement, Aurore L’Honoré, Catherine Gerbon, Jacques Demaille, Mireille Claustres and Marie-Catherine Romey, Binding of serum response factor to cystic fibrosis transmembrane conductance regulator CArG-like elements, as a new potential CFTR transcriptional regulation pathway.  Nucelic Acids Research,Vol. 33, No. 16, 5271-5290, 2005.


Suaud L, Rubenstein RC. Activation of STAT-3 in CF epithelial cell by Sodium 4-Phenylbutyrate. FASEB Journal 2005; 19 (4, Suppl. S, Part 1): A658.


Wright J.M., Zeitlin P.L., Cebotaru L., Guggino S.E., Guggino W.B., Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins.  Physiol Genomics 16:204-211, 2004.


Lim M., McKenzie K., Floyd A.D., Kwon E., Zeitlin P.L. Modulation of ΔF508 Cystic Fibrosis Transmembrane Regulator Trafficking and Function with 4-Phenylbutyrate and Flavonoids.  Am. J. Respir. Cell Mol. Biol. Vol. 31, pp. 351-357, 2004. 


Wang W-J., Mulugeta S., Russo S.J., Beers M.F., Deletion of exon 4 from human surfactant protein C results in aggresome formation and generation of a dominant negative, Journal of Cell Science 116, 683-692, 2003.


Roomans G.M. Pharmacological Approaches to Correcting the Ion Transport Defect in Cystic Fibrosis. Am J. Respir Med. 2003; 2(5):413-431


Poschet J.F., Skidmore J., Bouchjer J.C., Firoved A.M., Van Dyke R.W., Deretic V. Hyperacidification of Cellubrevin Endocytic Compartments and Defective Endosomal Recycling in Cystic Fibrosis Respiratory Epithelial Cells, The Journal of Biological Chemistry Vol. 277, No. 16, April 2002

Zeitlin, P., Diener-West, M., Rubenstein, R., Boyle, M., Lee, C., Brass-Ernst, L.  Evidence of CFTR Function in Cystic Fibrosis after Systemic Administration of 4-Phenylbutyrate.  Molecular Therapy, Vol. 6, No. 1, July 2002


Farinha Carols M., Nogueira, Paulo, Mendes, Filipa, Penque, Deborah and Amaral, Margarida D.  The human Dnaj homologue (Hdj)-1/heat-shock protein (Hsp) 40 co-chaperone is required for the in vivo stabilization of the cystic fibrosis transmembrane conductance regulator by Hsp70.  Biochem. J. (2002) 366, 797-806.

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Zhou Q, Guo W, Jia Y, Xu J. Effect of 4-Phenylbutyric Acid and Tauroursodeoxycholic Acid on Magnesium and Calcium Metabolism in Streptozocin-Induced Type 1 Diabetic Mice. Biol Trace Elm Res June 2019;189(2):501-510

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Gadallah SH, Ghanem HM, Abdel-Ghaffar A, Metwaly FG, Hanafy LK, Ahmed EK. 4-Phenylbutyric acid and rapamycin improved diabetic status in high fac diet/streptozotocin-induced type 2 diabetes through activation of autophagy. Arch Physiol Biochem. June 2019;1-10

Huang Kh, Suan SS, Lin WH, Wu CT, Sheu ML, Chiang CK, Liu SH. Role of Calbindin-D28k in Diabetes-Associated Advanced Renal Proximal Tubule Cell Injury. Cells June 2019;8(7):660

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Kong FJ, Ma LL, Guo JJ, Xu LH, Li Y, Q S. Endoplasmic reticulum stress/authophagy pathway is involved in diabetes-induced neuronal apoptosis and cognitive decline in mice. Clin Sci (Lond) Jan 2018;132(1):111-125

He Z, Zou S, Yin J, Gao Z, Liu Y, Wu Y, He H, Z Y, Wang Q, Li J, Wu F, Xu A, Jia X, Xiao J. Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury. Sci Rep Aug 2017;7(1):7661

Liu H, Yin JJ, Cao MM, Liu GD, Su Y, Li YB. Endoplasmic reticulum stress induced by lipopolysaccharide is involved in he association between inflammation and autophagy in INS-1 cells. Mol Med Rep Nov 2017;(16(5):5787-5792

Cheang WS, Wong WT, Zhao L, Xu J, Wang L, Lau CW, Chen ZY, Ma RCW, Xu A, Wang N, Tian XY, Huang Y. PPARδ Is Required for Exercise to Attenuate Endoplasmic Reticulum Stress and Endothelial Dysfunction in Diabetic Mice. Diabetes Feb 2017;66(2):519-528

Pomozi V, Brampton C, Szeri F, Dedinski D, Kozák E, van de Wetering K, Hopkins H, Martin L, Váradi A, LeSaux O. Functional Rescue of ABCC6 Deficiency by 4-Phenylbutyrate Therapy Reduces Dystrophic Calcification in Abcc6 -/- Mice. J Invest Dermatol Mar 2017;137(3):595-602

Montane J, de Pablo S, Castaño C, Rodríguez-Comas J, Cadavez L, Obach M, Visa M, Alcarras-Vizán G, Sanchez-Martinez M, Nonell-Canals A, Parizas M, Servitja JM, Novials A. Amyloid-induced ß-cell dysfunction and islet inflammation are ameliorate by 4-phenylbutyrate (PBA) treatment. FASEB J Dec 2017;(12):5296-5306

Guo R, Wu Z, Jiang J, Liu C, Wu B, Li X, Li T, Mo H, He S, Li S, Yan H, Huang R, You Q, Wu K. New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of Endogenous H2S Production and ER stress. Mech Ageing Dev Mar 2017; 162:46-52

Lombardi A, Tomer Y. Interferon alpha impairs insulin production in human beta cells via endoplasmic reticulum stress. J Autoimmun Jun 2017;80:48-55

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Hattori S, Kamiya T, Hara H, Ninomiya M, Koketsu M, Adachi T. CoCl2 Decreases EC-SOD Expression through Histone Deacetylation in COS7Cells. Bio Pharm Bull 2016;39(12):2036-2041

Zheng P, Lin Y, Wang F, Luo R, Zhang T, Hu S, Feng P, Liang X, Li C, Wang W. 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress. Am J Physiol Renal Physiol Oct 2016;311(4):F763-F776

Cao AL, Wang L, Chen X, Wang YM, Guo HJ, Chu S, Liu C, Zhang XM, Peng W. Ursodeoxycholic acid and 4-Phenylbutyrate prevent endoplasmic reticulum stressed-induced podocyte apoptosis in diabetic nephropathy. Lab Invest June 2016;96(6):610-22

Toma L, Sanda GM, Deleanu M, Stancu CS, Sim AV. Glycated LDL increase VCAM-1 expression and secretion in endothelial cells and promote monocyte adhesion through mechanisms involving endoplasmic reticulum stress. Mol Cell Biochem June 2016;417(1-2):169-79

Gu H, Yu J, Don D, Zhou Q, Wang JY, Fang S, Yang P. High Glucose-Repressed CITRD2 Expression Through miR-200b Triggers the Unfolded Protein Response and Endoplasmic Reticulum Strett. Diabetes Jan 2016;65(1):149-63

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Ji X, Yao L, Wang M, Liu X, Peng S, Li K, Xu M, Shen N, Luo L, Sun C. Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes. FEBS Lett Dec 2015;589(24Pt B):3938-44

Srinivasan K, Sharma SS. Sodium Phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid bype 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation. Behav Brain Res Nov 20, 2011; 225(1); 110-6

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