Disease relevance of NSC 295

• METHODS: A patient who had experienced multiple relapses was treated with all-trans-retinoic acid alone and in combination with sodium phenylbutyrate, an inhibitor of histone deacetylases [1].
• Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate [2].
• Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial [3].
• Patients with myelodysplastic syndrome or acute myeloid leukemia (AML) were treated with the methyltransferase inhibitor 5-azacitidine (aza-CR) followed by the histone deacetylase inhibitor sodium phenylbutyrate [4].
• Taken together, our results raise the possibility that NaPA or sodium phenylbutyrate taken through drinking water or milk may reduce the observed neuroinflammation and disease process in multiple sclerosis patients [5].

High impact information on NSC 295

• However, 23 days after sodium phenylbutyrate was added to the treatment regimen, visible leukemic cells had been eliminated from her bone marrow, and she achieved a complete clinical and cytogenetic remission shortly thereafter [1].
• These elevated mRNAs were significantly reduced in HD patients involved in a dose-finding study of the histone deacetylase inhibitor sodium phenylbutyrate [6].
• In summary, the AI-deficient mouse duplicates several pathobiological aspects of the human condition and should prove to be a useful model for further study of the disease mechanism(s) and to explore treatment options, such as pharmaceutical administration of sodium phenylbutyrate and/or ornithine and development of gene therapy protocols [7].
• Oral administration of sodium 4-phenylbutyrate rapidly increases F-cell production in sickle cell disease [2].
• We show here that sodium phenylacetate (NaPA) and its precursor, sodium 4-phenylbutyrate (NaPB), can enhance HbF production in cultured erythroid progenitor derived from normal donors and patients with SS anemia or beta-thal, when used at pharmacologic concentrations [8].

Chemical compound and disease context of NSC 295

• In this study we show that the chemical chaperone, glycerol, and the transcriptional regulator, sodium 4-phenylbutyrate, inhibit the constitutively activated inward current and reduce cell growth and migration in glioblastoma multiforme [9].
• Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome [10].
• Hydroxyurea (HU) and sodium phenylbutyrate (SPB) have been shown to increase fetal hemoglobin (Hb F) levels in patients with thalassemia intermedia [11].

Biological context of NSC 295

• Immunofluorescence microscopy and cell surface biotinylation showed that treatment with sodium 4-phenylbutyrate rescued several of the missense mutants from the ER to the cell surface [12].
• Colchicine and sodium 4-phenylbutyrate treatment increased secretion of THP from the ER to the cell membrane and into the culture media and significantly improved cell viability [13].
• A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies [14].
• Sodium phenylbutyrate (NaPB) represent a new non-toxic class of compounds with antiproliferative activities to different tumors and has been shown to modulate many gene expressions by inhibiting histone deacetylation and DNA methylation as the major mechanism [15].
• A successful pregnancy in a heterozygote for OTC deficiency treated with sodium phenylbutyrate [16].

Anatomical context of NSC 295

• After treatment of PBD fibroblasts with sodium 4-phenylbutyrate, a human peroxisome proliferator, there was an approximate twofold increase in peroxisome number [17].
• Because sodium 4-phenylbutyrate has been shown to function as a chemical chaperone and to correct the cellular trafficking of several mislocalized or misfolded mutant plasma membrane proteins, the effects of this compound on the missense mutants identified in patients with congenital nephrotic syndrome of the Finnish type were investigated [12].
• Sodium phenylacetate (PA) and sodium phenylbutyrate (PB) are aromatic fatty acids that can effect differentiation in a variety of cell lines at doses that may be clinically attainable [18].
• Sodium phenylbutyrate (PB) is an aromatic fatty acid with cytostatic and differentiating activity against malignant myeloid cells (ID(50), 1-2 mM) [19].
• Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis [20].

Associations of NSC 295 with other chemical compounds

• EXPERIMENTAL DESIGN AND RESULTS: Nanomolar concentrations of trichostatin A induced growth arrest in five of seven NSCLC cell lines, whereas sodium phenylbutyrate (PB) was markedly less potent [21].
• We performed a randomized, double-blind, placebo-controlled, dose-escalation and safety study of Buphenyl in 19 adults with CF (homozygous deltaF508) to test the hypothesis that Buphenyl would be safe, well-tolerated, and associated with an increase in chloride transport in nasal epithelia [22].
• METHODS: CHO-K1, HEK293 and human trabecular meshwork cells were transfected to express wild-type or mutant (C245Y, G364V, P370L, Y437H) myocilin-green fluorescent protein fusion protein and were treated or not with various chemical chaperones (glycerol, dimethylsulfoxide, or sodium 4-phenylbutyrate) for different time periods [20].
• All the lipases tested in the present study can catalyse the hydrolysis of pure fatty acid anhydrides more efficiently than that of glycerol tributyrate [23].
• Tributyrin (glyceryl tributyrate, TB) is known to induce malignant cells to differentiate followed by arrest of cell growth and death via apoptosis [24].

Gene context of NSC 295

• Sodium 4-phenylbutyrate (4PBA) improves DeltaF508-CFTR trafficking and function in vitro in cystic fibrosis epithelial cells and in vivo [25].
• Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines [26].
• Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR [25].
• Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway [27].
• Treatment of those cells with the chemical chaperone sodium 4-phenylbutyrate could partially restore trafficking of mutant ABCA3 to lamellar body-like structures [28].

Analytical, diagnostic and therapeutic context of NSC 295

• The administration of a test dose of sodium phenylbutyrate to the control group did not affect the rate of [15N]urea formation [29].
• We performed a retrospective study in nine patients (four male/five female, age at diagnosis ranging from 6 days to 14 years) to evaluate the safety and efficacy of sodium phenylbutyrate (Ammonaps) in long-term treatment [30].
• Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis [31].
• Although this retrospective series is not really representative of the modern treatment combining low protein diet and arginine, sodium benzoate and sodium phenylbutyrate, it is obvious that the long-term outcome of all urea cycle disorders remains very guarded [32].
• Sodium 4-phenylbutyrate (4-SPB), an aromatic derivative of butyric acid, was examined to elucidate its effect on islet engraftment in a syngeneic transplantation model using C57BL/6 mice [33].

References