Phenylbutyrate (PB)

Dvorit D. SAMID learned about PHENYLBUTYRATE (PB) from Burzynski
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Antineoplastons AS2-1 and AS2-5 are DERIVED FROM A10
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Phenylacetylglutaminate (PAG or PG) and Phenylacetate (PN) are metabolites of PHENYLBUTYRATE (PB) and are constituents of antineoplaston AS2-1
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National Cancer Institute (NCI)
at the National Institutes of Health (NIH) Antineoplastons
General Information:
http://www.cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/page2
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Sodium PHENYLBUTYRATE (PB)
Year – Pubmed (110 entries)
1958 1st entry
1995 1st clinical trial
2001 Phase 1
2009 Phase 2
2012 Phase 3
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PHENYLBUTYRATE (PB)
19 (PHENYLBUTYRATE (PB + SAMID)
http://www.ncbi.nlm.nih.gov/m/pubmed/?term=Phenylbutyrate+Samid
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IV. Aetna considers SODIUM PHENYLBUTYRATE medically necessary for the treatment of acute promyelocytic leukemia and malignant glioma
http://www.aetna.com/cpb/medical/data/200_299/0240.html
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The FDA has approved SODIUM PHENYLBUTYRATE as a treatment to remove ammonia from the bloodstream in individuals with urea cycle disorders
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SODIUM PHENYLBUTYRATE was given an orphan drug designation by the FDA for use as an adjunct to surgery, radiation therapy, and chemotherapy for treatment of individuals with primary or recurrent malignant glioma
http://www.anthem.com/medicalpolicies/policies/mp_pw_a050524.htm
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Cumulative List of all Products that have received Orphan Designation: Total active designations: 2002 Effecive: (sic – Effective) 5/5/2009
http://www.fda.gov/downloads/forindustry/developingproductsforrarediseasesconditions/howtoapplyfororphanproductdesignation/ucm162066.xls
PHENYLBUTYRATE (PB) and SODIUM PHENYLBUTYRATE are listed alphabetically in the lower 1/4th of this document
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Pubmed 110 entries
Sodium PHENYLBUTYRATE
“Sodium PHENYLBUTYRATE (aka PB) …”
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If they’re going to include it in a phase 3 study, than it’s “fair game”
http://www.ncbi.nlm.nih.gov/m/pubmed/22961727
Hepatology
Early View (Online Version of Record published before inclusion in an issue)

Article first published online: 3 JAN 2013

DOI: 10.1002/hep.26058
http://onlinelibrary.wiley.com/doi/10.1002/hep.26058/abstract;jsessionid=34AE3D61DEEF5356F147DE74B26759F9.d01t03
Article:
http://onlinelibrary.wiley.com/doi/10.1002/hep.26058/full
References:
http://onlinelibrary.wiley.com/doi/10.1002/hep.26058/references
Cited by:
http://onlinelibrary.wiley.com/doi/10.1002/hep.26058/citedby

Hepatology. 2012 Sep 7. doi: 10.1002/hep.26058. [Epub ahead of print]
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1990 – Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1.
http://www.ncbi.nlm.nih.gov/m/pubmed/2152694/
BURZYNSKI, S. R., Kubove E., Burzynski, B.
Drugs Exp. Clin. Res., 16: 361-369, 1990.
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1991 – Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/
SAMID D., Shack S., Myers C.
J. Clin. Investig., 91: 2288-2295, 1991.
J Clin Invest. 1993 May; 91(5): 2288–2295.
doi: 10.1172/JCI116457
PMCID: PMC288233

References:

SAMID D, Flessate DM, Friedman RM. Interferon-induced revertants of ras-transformed cells:

resistance to transformation by specific oncogenes and retransformation by 5-azacytidine. Mol Cell Biol. 1987 Jun;7(6):2196–2200.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC365343/

http://www.ncbi.nlm.nih.gov/m/pubmed/2439904/
SAMID D, Shack S, Sherman LT. Phenylacetate:

a novel nontoxic inducer of tumor cell differentiation. Cancer Res. 1992 Apr 1;52(7):1988–1992.
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/

http://cancerres.aacrjournals.org/content/52/7/1988
SAMID D, Yeh A, Prasanna P. Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate. Blood. 1992 Sep 15;80(6):1576–1581.
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/
Dover GJ, Brusilow S, SAMID D. Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE. N Engl J Med. 1992 Aug 20;327(8):569–570.
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
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4/1/1992Phenylacetate:

A novel non-toxic inducer of tumor cell differentiation
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
SAMID D, Shack S , Sherman L T
http://cancerres.aacrjournals.org/content/52/7/1988
Cancer Res 52:1988,1992
Cancer Res. 1992 Apr 1;52(7):1988-92.
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland.
↵1 Supported by Elan Pharmaceutical Corporation Grant G174ED.
Reference: 12 (SAMID, D.)
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8/20/1992 – Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE.
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
Dover GJ, Brusilow S, SAMID D
N Engl J Med 327569, 1992
N Engl J Med. 1992 Aug 20;327(8):569–570.
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9/15/1992 – Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate.
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/
SAMID D, Yeh A, Prasanna P
Blood 80:1576, 1992
Blood. 1992 Sep 15;80(6):1576–1581.
Blood. 1992 Sep 15;80(6):1576-81.
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD.

References:

15. SAMID D, Shack S, Ti-Sherman L Phenylacetate-A novel nontoxic inducer of tumor cell differentiation. Cancer Res 52:1988, 1992
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
Cancer Res. 1992 Apr 1;52(7):1988-92.
http://cancerres.aacrjournals.org/content/52/7/1988
20. SAMID D, Flessate DM, Friedman RM: Interferon-induced revertants of ras-transformed cells:

Resistance to transformation by specific oncogenes and retransformation by 5-azacytidine. Mol Cell Biol7:2196,1987
http://www.ncbi.nlm.nih.gov/m/pubmed/2439904/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC365343/
21. Rimoldi D, Srikantan V, Wilson VL, Bassin RH,SAMID D: Increased sensitivity of nontumorigenic fibroblasts expressing ras or myconcogenes to malignant transformation induced by 5-aza-2‘- deoxycytidine. Cancer Res 51:324,1991
http://www.ncbi.nlm.nih.gov/m/pubmed/1703037/

http://m.cancerres.aacrjournals.org/content/51/1/324.abstract

http://m.cancerres.aacrjournals.org/content/51/1/324.full.pdf

http://cancerres.aacrjournals.org/content/51/1/324
34. Dover GJ, Brusilow S, SAMID D: Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE. N Engl J Med 327569,1992
N Engl J Med. 1992 Aug 20;327(8):569–570.
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
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5/1993 – Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic, pharmacological concentrations of phenylacetate.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/
SAMID D, Shack S, Myers CE:
J Clin Invest 91:2288, 1993
J Clin Invest. 1993 May; 91(5): 2288–2295.
doi: 10.1172/JCI116457
PMCID: PMC288233

References:

9. SAMID D, Flessate DM, Friedman RM. Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine. Mol Cell Biol. 1987 Jun;7(6):2196–2200.
http://www.ncbi.nlm.nih.gov/m/pubmed/2439904/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC365343/

http://mcb.asm.org/content/7/6/2196.full.pdf
13. SAMID D, Shack S, Sherman LT. Phenylacetate:

a novel nontoxic inducer of tumor cell differentiation. Cancer Res. 1992 Apr 1;52(7):1988–1992.
Cancer Res 52:1988, 1992
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
Cancer Res. 1992 Apr 1;52(7):1988-92.
http://cancerres.aacrjournals.org/content/52/7/1988
14. SAMID D, Yeh A, Prasanna P. Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate. Blood. 1992 Sep 15;80(6):1576–1581.
Blood 80:1576, 1992
Blood. 1992 Sep 15;80(6):1576-81.
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/
17. Dover GJ, Brusilow S, SAMID D. Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE. N Engl J Med. 1992 Aug 20;327(8):569–570.
N Engl J Med 327569,1992
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
33. D. SAMID
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10/1/1993 – Enhanced fetal
hemoglobin production by phenylacetate and 4-PHENYLBUTYRATE in erythroid precursors derived from normal blood donors and patients with sickle cell anemia and P-thalassemia
http://www.ncbi.nlm.nih.gov/m/pubmed/7691251/
Fibach E, Prasanna P, Rodgers GP, SAMID D:
Blood 822203, 1993
Blood. 1993 Oct 1;82(7):2203-9.
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.

References:

15. (SAMID D)

19. SAMID D, Yeh A, Prasanna P Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate. Blood 80:1576, 1992
Blood. 1992 Sep 15;80(6):1576–1581.
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/
20. Dover GJ, Brusilow S, SAMID D: Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE. N Engl J Med 327569, 1992
N Engl J Med. 1992 Aug 20;327(8):569–570.
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
3I. SAMID D, Shack S, Ti-Sherman L Phenylacetate-A novel
nontoxic inducer of tumor cell differentiation. Cancer Res 52:1988, 1992
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
Cancer Res. 1992 Apr 1;52(7):1988-92.
http://cancerres.aacrjournals.org/content/52/7/1988
32. SAMID D, Shack S, Myers CE: Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic, pharmacological concentrations of phenylacetate. J Clin Invest 91:2288, 1993
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/
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4/1/1994 Phase 1
http://www.ncbi.nlm.nih.gov/m/pubmed/8137283
A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer
http://m.cancerres.aacrjournals.org/content/54/7/1690.abstract
Thibault A, Cooper MR, Figg WD, Venzon DJ, Sartor AO, Tompkins AC, Weinberger MS, Headlee DJ, McCall NA, SAMID D, et al.
http://m.cancerres.aacrjournals.org/content/54/7/1690.full.pdf
Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, Maryland
Cancer Res. 1994 Apr 1;54(7):1690-4.
Cancer Res 54(7):1690-4 (1994), PMID.8137283
recent version of this article at: http://cancerres.aacrjournals.org/content/54/7/1690
References:

8. SAMID, A., Shack, S., and Sherman, L. T. Phenylacetate:

a novel nontoxic inducer of tumor cell differentiation. Cancer Res., 52: 1988-1992, 1992.
Cancer Res 52:1988, 1992
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
Cancer Res. 1992 Apr 1;52(7):1988-92.
http://cancerres.aacrjournals.org/content/52/7/1988
9. SAMID, D., Yen, A., and Prasana, P. Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate. Blood, 80: 1576-1581, 1992.
Blood 80:1576, 1992
Blood. 1992 Sep 15;80(6):1576–1581.
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/
10. SAMID, D., Shack, S., and Myers, C. E. Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J. Clin. Invest., 91: 2288-2295, 1993.
J Clin Invest 91:2288, 1993
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/
11. SAMID. D., Ram, Z., Hudgins, W. R., Shack, S., Liu, L., Walbridge, S., Oldfield, E. H., Myers, C. E. Selective activity of phenylacetate against malignant gliomas:

resemblance to fetal brain damage in phenylketonuria. Cancer Res., 54: 891-895, 1994.
http://www.ncbi.nlm.nih.gov/m/pubmed/8313377/
12. Dover, G. J., Brusilow, S., and SAMID, D. Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE. N. Engl. J. Med., 327: 569-570, 1992.
N Engl J Med 327569, 1992
N Engl J Med. 1992 Aug 20;327(8):569–570.
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
13. BURZYNSKI, S. R., Kubove E., Burzynski, B. Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp. Clin. Res., 16: 361-369, 1990.
http://www.ncbi.nlm.nih.gov/m/pubmed/2152694/
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1/1/1995 1st clinical trial
http://www.ncbi.nlm.nih.gov/m/pubmed/7528572
Oral sodium PHENYLBUTYRATE therapy in homozygous beta thalassemia:

a clinical trial
http://m.bloodjournal.hematologylibrary.org/content/85/1/43.full.pdf#page=1
Collins AF, Pearson HA, Giardina P, McDonagh KT, Brusilow SW, Dover GJ.
Blood. 1995 Jan 1;85(1):43-9.
Johns Hopkins University School of Medicine, Baltimore, MD.

References:

14. SAMID D, Shack S , Sherman L T

Phenylacetate:

A novel non-toxic inducer of tumor cell differentiation
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
Cancer Res 52:1988,1992
Cancer Res. 1992 Apr 1;52(7):1988-92.
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland.
http://cancerres.aacrjournals.org/content/52/7/1988
16. Fibach E, Prasanna P, Rodgers GP, SAMID D:

Enhanced fetal
hemoglobin production by phenylacetate and 4-PHENYLBUTYRATE in erythroid precursors derived from normal blood donors and patients with sickle cell anemia and P-thalassemia
http://www.ncbi.nlm.nih.gov/m/pubmed/7691251/
Blood 822203, 1993
Blood. 1993 Oct 1;82(7):2203-9.
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.

28. Dover GJ, Brusilow SW, SAMID D:

Increased fetal hemoglobin in patients receiving sodium 4-PHENYLBUTYRATE
http://www.ncbi.nlm.nih.gov/m/pubmed/1378939/
N Engl JMed 327:569, 1992 (letter)
N Engl J Med. 1992 Aug 20;327(8):569-70.
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7/1995 – Transcriptional upregulation of TGF-α by phenylacetate and PHENYLBUTYRATE is associated with differentiation of human melanoma cells.
http://www.ncbi.nlm.nih.gov/m/pubmed/7578983/
Liu L., Hudgins W. R., Miller A. C., Chen L. C., SAMID D.
http://www.sciencedirect.com/science/article/pii/S1043466685700610
Cytokine, 7: 449-456, 1995.
Cytokine Volume 7, Issue 5, July 1995, Pages 449–456
Cytokine. 1995 Jul;7(5):449-56.
a Clinical Pharmacology Branch, National Cancer Institute, Armed Forces of Radiation Research Institute, Bethesda, Maryland, USA
b Radiation Biochemistry Department, Armed Forces of Radiation Research Institute, Bethesda, Maryland, USA
http://dx.doi.org/10.1006/cyto.1995.0061
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8/23/1996 – Activation of the human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogues.
http://www.ncbi.nlm.nih.gov/m/pubmed/8759039/
Pineau T., Hudgins W. R., Liu L., Chen L. C., Sher T., Gonzalez F. J., SAMID D.
http://www.sciencedirect.com/science/article/pii/0006295296003401
Biochem. Pharmacol., 52: 659-667, 1996.
Biochemical Pharmacology
Volume 52, Issue 4, 23 August 1996, Pages 659–667
Biochem Pharmacol. 1996 Aug 23;52(4):659-67.
∗ Laboratory of Molecular Carcinogenesis U.S.A.
‡ Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD U.S.A.
§ Experimental Therapeutics Program, University of Virginia Cancer Center, Charlottesville, VA, U.S.A.
http://dx.doi.org/10.1016/0006-2952(96)00340-1
This work was supported, in part, by funds from the Elan Pharmaceutical Research Corporation through a Cooperative Research and Development Agreement (CACR-0139).
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9/1996 – The differentiating agent phenylacetate increases prostate-specific antigen production by prostate cancer cells.
http://www.ncbi.nlm.nih.gov/m/pubmed/8827086/
Walls R., Thibault A., Liu L., Wood C., Kozlowski J. M., Figg W. D., Sampson M. L., Elin R. J., SAMID D.
Prostate, 29: 177-182, 1996.
Prostate. 1996 Sep;29(3):177-82.
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland, USA.
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10/25/1996 – Transcriptional upregulation of γ globin by PHENYLBUTYRATE and analogous aromatic fatty acids.
http://www.ncbi.nlm.nih.gov/m/pubmed/8937430/
Hudgins W. R., Fibach E., Safaya S., Rieder R. F., Miller A. C., SAMID D.
http://www.sciencedirect.com/science/article/pii/0006295296004765
Biochem. Pharmacol., 52: 1227-1233, 1996.
Biochem Pharmacol. 1996 Oct 25;52(8):1227-33.
Biochemical Pharmacology
Volume 52, Issue 8, 25 October 1996, Pages 1227–1233
a Clinical Pharmacology Branch, National Cancer Institute, and Laboratory of Chemical Biology, National Institute of Diabetes, Digestive Diseases and Kidney Diseases, National Institutes Of Health, Bethesda, MD, U.S.A.
b Department of Hematology, Hadassah University Hospital, Jerusalem, Israel
c Department of Medicine, State University of New York Health Science Center, Brooklyn, NY, U.S.A.
d Radiation Biochemistry Department, Armed Forces Radiation Research Institute, Bethesda, MD, U.S.A.
e University of Virginia Cancer Center, Charlottesville, VA, U.S.A.
http://dx.doi.org/10.1016/0006-2952(96)00476-5

This work was supported by funds from the Elan Pharmaceutical Research Corp. and from the Israeli Science Foundation, administered by the Israel Academy of Sciences and Humanities.
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1997 – The nuclear receptors PPARS as novel targets in differentiation therapy: activation by phenylacetate and PHENYLBUTYRATE .
SAMID D., Wells M., Kulkarni M., Lei L., Thibault A.
Anticancer Res., 17: 3927-3928, 1997.
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8/2001 – A phase Idose escalation and bioavailability study of oral sodium PHENYLBUTYRATE in patients with refractory solid tumor malignancies
http://www.ncbi.nlm.nih.gov/m/pubmed/11489804
J Gilbert, S D Baker, … M A Carducci
http://m.clincancerres.aacrjournals.org/content/7/8/2292.long
Clin Cancer Res 7(8):2292-300 (2001), PMID.11489804

Clin Cancer Res. 2001 Aug;7(8):2292-300

References:

2. ↵ Liu L., Hudgins W. R., Miller A. C., Chen L. C., SAMID D. Transcriptional upregulation of TGF-α by phenylacetate and PHENYLBUTYRATE is associated with differentiation of human melanoma cells. Cytokine, 7: 449-456, 1995.
http://www.ncbi.nlm.nih.gov/m/pubmed/7578983/

http://www.sciencedirect.com/science/article/pii/S1043466685700610
3. ↵ Hudgins W. R., Fibach E., Safaya S., Rieder R. F., Miller A. C., SAMID D. Transcriptional upregulation of γ globin by PHENYLBUTYRATE and analogous aromatic fatty acids. Biochem. Pharmacol., 52: 1227-1233, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/8937430/

http://www.sciencedirect.com/science/article/pii/0006295296004765
5. ↵ SAMID D., Shack S., Myers C. E. Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J. Clin. Investig., 91: 2288-2295, 1991.
http://www.ncbi.nlm.nih.gov/m/pubmed/8486788/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/

http://m.jci.org/articles/view/116457
6. ↵ Pineau T., Hudgins W. R., Liu L., Chen L. C., Sher T., Gonzalez F. J., SAMID D. Activation of the human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogues. Biochem. Pharmacol., 52: 659-667, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/8759039/

http://www.sciencedirect.com/science/article/pii/0006295296003401
15. ↵ Walls R., Thibault A., Liu L., Wood C., Kozlowski J. M., Figg W. D., Sampson M. L., Elin R. J., SAMID D. The differentiating agent phenylacetate increases prostate-specific antigen production by prostate cancer cells. Prostate, 29: 177-182, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/8827086/
20. ↵ SAMID D., Wells M., Kulkarni M., Lei L., Thibault A. The nuclear receptors PPARS as novel targets in differentiation therapy: activation by phenylacetate and PHENYLBUTYRATE. Anticancer Res., 17: 3927-3928, 1997.
� � � � � � � � � � � � � � � � �
10/2001 – A Phase I clinical and pharmacological evaluation of sodium PHENYLBUTYRATE on an 120-h infusion schedule
M A Carducci, J Gilbert, … R C Donehower
Clin Cancer Res 7(10):3047-55 (2001), PMID.11595694
http://www.ncbi.nlm.nih.gov/m/pubmed/11595694
Clin Cancer Res. 2001 Oct;7(10):3047-55.
http://m.clincancerres.aacrjournals.org/content/7/10/3047.long
Division of Medical Oncology, The Johns Hopkins Oncology Center, Baltimore, MD, USA.

References:

10. ↵ SAMID D., Shack S., Myers C. E. Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J. Clin. Investig., 91: 2288-2295, 1991.
http://www.ncbi.nlm.nih.gov/m/pubmed/8486788/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/

http://m.jci.org/articles/view/116457

http://m.jci.org/articles/view/116457/pdf.mobile
11. ↵ SAMID D., Shack S., Sherman L. T. Phenylacetate:

a novel nontoxic inducer of tumor cell differentiation. Cancer Res., 52: 1988-1992, 1992.
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/

http://m.cancerres.aacrjournals.org/content/52/7/1988.abstract

http://m.cancerres.aacrjournals.org/content/52/7/1988.full.pdf

http://cancerres.aacrjournals.org/content/52/7/1988
13. ↵ Shack S., Miller A., Liu L., Prasanna P., Thilbault A., SAMID D. Vulnerability of multi-drug resistant tumor cells to the aromatic fatty acids phenylacetate and PHENYLBUTYRATE. Clin. Cancer Res., 2: 865-872, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/9816242/

http://m.clincancerres.aacrjournals.org/content/2/5/865.abstract

http://m.clincancerres.aacrjournals.org/content/2/5/865.full.pdf

http://clincancerres.aacrjournals.org/content/2/5/865
14. ↵ SAMID D., Yeh A., Prasanna P. Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate. Blood, 80: 1576-1581, 1992.
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/

http://m.bloodjournal.hematologylibrary.org/content/80/6/1576.abstract

http://m.bloodjournal.hematologylibrary.org/content/80/6/1576.full.pdf
17. ↵ SAMID D., Ram Z., Hudgins W. R., Shack S., Liu L., Walbridge S., Oldfield E. H., Myers C. E. Selective activity of phenylacetate against malignant gliomas:

resemblance to fetal brain damage in phenylketonuria. Cancer Res., 54: 891-895, 1994.
http://www.ncbi.nlm.nih.gov/m/pubmed/8313377/

http://cancerres.aacrjournals.org/content/54/4/891/
18. ↵ Fibach E., Prasanna P., Rodgers G. P., SAMID D. Enhanced fetal hemoglobin production by phenylacetate and 4-PHENYLBUTYRATE in erythroid precursors derived from normal donors and patients with sickle cell anemia and β-thalassemia. Blood, 82: 2203-2209, 1993.
http://www.ncbi.nlm.nih.gov/m/pubmed/7691251/

http://m.bloodjournal.hematologylibrary.org/content/82/7/2203.abstract

http://m.bloodjournal.hematologylibrary.org/content/82/7/2203.full.pdf
23. ↵ Liu L., Hudgins W. R., Miller A. C., Chen L. C., SAMID D. Transcriptional upregulation of TGF-α by phenylacetate and PHENYLBUTYRATE is associated with differentiation of human melanoma cells. Cytokine, 7: 449-456, 1995.
http://www.ncbi.nlm.nih.gov/m/pubmed/7578983/

http://www.sciencedirect.com/science/article/pii/S1043466685700610
24. ↵ Hudgins W. R., Fibach E., Safaya S., Reider R. F., Miller A. C., SAMID D. Transcriptional upregulation of γ globin by PHENYLBUTYRATE and analogous aromatic fatty acids. Biochem. Pharmacol., 52: 1227-1233, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/8937430/

http://www.sciencedirect.com/science/article/pii/0006295296004765
27. ↵ Pineau T., Hudgins W. R., Liu L., Chen L. C., Sher T., Gonzalez F. J., SAMID D. Activation of human peroxisome proliferator activator receptor by the antitumor agent phenylacetate and its analogs. Biochem. Pharmacol., 52: 659-667, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/8759039/

http://www.sciencedirect.com/science/article/pii/0006295296003401
33. ↵ Walls R., Thilbault A., Liu L., Wood C., Kozlowski J. M., Figg W. D., Sampson M. L., Elin R. J., SAMID D. The differentiating agent phenylacetate increases prostate-specific antigen production by prostate cancer cells. Prostate, 29: 177-182, 1996.
http://www.ncbi.nlm.nih.gov/m/pubmed/8827086/
40. ↵ Thibault A., Cooper M. R., Figg W. D., Venzon D. J., Sartor A. O., Tompkins A. C., Weinberger M S., Headlee D. J., McCall N. A., SAMID D., et al A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer. Cancer Res., 54: 1690-1694, 1994.
http://www.ncbi.nlm.nih.gov/m/pubmed/8137283/

http://m.cancerres.aacrjournals.org/content/54/7/1690.abstract

http://m.cancerres.aacrjournals.org/content/54/7/1690.full.pdf

http://cancerres.aacrjournals.org/content/54/7/1690
41. ↵ Piscitelli S. C., Thibault A., Figg W. D., Tompkins A. C., Headlee D., Lieberman R., SAMID D., Myers C. E. Disposition of PHENYLBUTYRATE and its metabolites, phenylacetate and phenylacetylglutamine. J. Clin. Pharmacol., 35: 368-373, 1995.
http://www.ncbi.nlm.nih.gov/m/pubmed/7650225/

http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1995.tb04075.x/abstract;jsessionid=43600D49608A093971D675F3DB5FF13D.d01t03
47. ↵ SAMID D., Wells M., Kulkarni M., Lei L., Thibault A. The nuclear receptors PPARS as novel targets in differentiation therapy:

activation by phenylacetate and PHENYLBUTYRATE. Anticancer Res., 17: 3927-3928, 1997
� � � � � � � � � � � � � � � � �
4/2005 – Oral sodium PHENYLBUTYRATE in patients with recurrent malignant gliomas:

A dose escalation and pharmacologic study

Neuro-oncol. 2005 April; 7(2): 177–182 PMCID: PMC1871887

PDF:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871887/pdf/neu0702p177.pdf
References:

3. Buckner JC, Malkin MG, Reed E, Cascino TL, Reid JM, Ames MM, Tong WP, Lim S, Figg WD

Phase II study of anti-neoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma

Mayo Clin Proc. 1999;74:137–145

12. Gore SD, SAMID D, Weng LJ

Impact of the putative differentiating agents sodium PHENYLBUTYRATE and sodium phenylacetate on proliferation, differentiation, and apoptosis of primary neoplastic myeloid cells

Clin Cancer Res. 1997a;3:1755–1762

17. Hudgins WR, Pineau T, Sher T, Gonzales FJ, Myers CE, SAMID D

Anticancer activity of phenylacetate and related aromatic fatty acids:

Correlation with lipophilicity and capacity to activate nuclear receptor

Proc Am Assoc Can Res. 1994;35:391. (abstract 2332)

19. SAMID D, Shack S, Myers CE

Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate

J Clin Invest. 1993;91:2288–2295

20. SAMID D, Ram Z, Hudgins WR, Shack S, Liu L, Walbridge S, Oldfield EH, Myers CE

Selective activity of phenylacetate against malignant gliomas:

Resemblance to fetal brain damage in phenylketonuria

Cancer Res. 1994;54:891–895

21. Sidell N, Wada R, Han G, Chang B, Shack S, Moore T, SAMID D

Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells

Int J Cancer. 1995;60:507–514
� � � � � � � � � � � � � � � � �
4/2005 – Oral sodium PHENYLBUTYRATE in patients with recurrent malignant gliomas:

A dose escalation and pharmacologic study

Neuro-oncol. 2005 April; 7(2): 177–182 PMCID: PMC1871887

PDF:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871887/pdf/neu0702p177.pdf
References:

3. Buckner JC, Malkin MG, Reed E, Cascino TL, Reid JM, Ames MM, Tong WP, Lim S, Figg WD
http://www.ncbi.nlm.nih.gov/m/pubmed/10069350
Phase II study of anti-neoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma
http://www.mayoclinicproceedings.org/article/S0025-6196(11)63835-4/fulltext
Mayo Clin Proc. 1999;74:137–145
http://linkinghub.elsevier.com/retrieve/pii/S0025-6196(11)63835-4
Mayo Clinic Proceedings
http://www.sciencedirect.com/science/article/pii/S0025619611638354
Mayo Clin Proc 74(2):9 (1999)
http://download.journals.elsevierhealth.com/pdfs/journals/0025-6196/PIIS0025619611638354.pdf
DOI: 10.4065/74.2.137
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2003.01098.x/full
Mayo Clin Proc 1999; 74: 137–45
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2003.01098.x/references

http://onlinelibrary.wiley.com/store/10.1046/j.1365-2796.2003.01098.x/asset/j.1365-2796.2003.01098.x.pdf?v=1&t=hbs6xce2&s=3423e3cd1955667e8e8cdf33323faf0bd85b6a29

http://onlinelibrary.wiley.com/store/10.1046/j.1365-2796.2003.01098.x/asset/j.1365-2796.2003.01098.x.pdf?v=1&t=hbrndkdf&s=e0af2d3bfb13841852d92a839d3a4932a5f4bb48
12. Gore SD, SAMID D, Weng LJ

Impact of the putative differentiating agents sodium PHENYLBUTYRATE and sodium phenylacetate on proliferation, differentiation, and apoptosis of primary neoplastic myeloid cells

Clin Cancer Res. 1997a;3:1755–1762
http://www.ncbi.nlm.nih.gov/m/pubmed/9815560/

http://m.clincancerres.aacrjournals.org/content/3/10/1755.abstract

http://m.clincancerres.aacrjournals.org/content/3/10/1755.full.pdf

http://clincancerres.aacrjournals.org/content/3/10/1755
17. Hudgins WR, Pineau T, Sher T, Gonzales FJ, Myers CE, SAMID D

Anticancer activity of phenylacetate and related aromatic fatty acids:

Correlation with lipophilicity and capacity to activate nuclear receptor

Proc Am Assoc Can Res. 1994;35:391. (abstract 2332)

19. SAMID D, Shack S, Myers CE

Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate

J Clin Invest. 1993;91:2288–2295
http://www.ncbi.nlm.nih.gov/m/pubmed/8486788/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288233/

http://m.jci.org/articles/view/116457
20. SAMID D, Ram Z, Hudgins WR, Shack S, Liu L, Walbridge S, Oldfield EH, Myers CE

Selective activity of phenylacetate against malignant gliomas:

Resemblance to fetal brain damage in phenylketonuria

Cancer Res. 1994;54:891–895
http://www.ncbi.nlm.nih.gov/m/pubmed/8313377/

http://cancerres.aacrjournals.org/content/54/4/891
21. Sidell N, Wada R, Han G, Chang B, Shack S, Moore T, SAMID D

Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells

Int J Cancer. 1995;60:507–514
http://www.ncbi.nlm.nih.gov/m/pubmed/7829265/
� � � � � � � � � � � � � � � � �
4/2007Phase I dose escalation clinical trial of PHENYLBUTYRATE sodium administered twice daily to patients with advanced solid tumors
Luis H LH Camacho, Jon J Olson, … Mark G MG Malkin
Invest New Drugs 25(2):131-8 (2007), PMID.17053987

Investigational New Drugs
April 2007, Volume 25, Issue 2, pp 131-138
http://www.ncbi.nlm.nih.gov/m/pubmed/17053987

http://link.springer.com/article/10.1007%2Fs10637-006-9017-4
References:

4. SAMID D, Shack S, Sherman LT

(1992)

Phenylacetate:

a novel nontoxic inducer of tumor cell differentiation

Cancer Res 52(7):1988–1992
http://www.ncbi.nlm.nih.gov/m/pubmed/1372534/
Cancer Res 52:1988,1992
Cancer Res. 1992 Apr 1;52(7):1988-92.
http://cancerres.aacrjournals.org/content/52/7/1988
5. DiGiuseppe JA, Weng LJ, Yu KH, Fu S, Kastan MB, SAMID D, et al

(1999)

PHENYLBUTYRATE-induced G1 arrest and apoptosis in myeloid leukemia cells:

structure-function analysis

Leukemia 13(8):1243–1253
http://www.ncbi.nlm.nih.gov/m/pubmed/10450753/
7. SAMID D, Hudgins WR, Shack S, Liu L, Prasanna P, Myers CE

(1997)

Phenylacetate and PHENYLBUTYRATE as novel, nontoxic differentiation inducers

Adv Exp Med Biol 400A:501–505
http://www.ncbi.nlm.nih.gov/m/pubmed/9547596/
20. Boudoulas S, Lush RM, McCall NA, SAMID D, Reed E, Figg WD

(1996)

Plasma protein binding of phenylacetate and PHENYLBUTYRATE, two novel antineoplastic agents

Ther Drug Monit 18(6):714–720
http://www.ncbi.nlm.nih.gov/m/pubmed/8946671/
24. Thibault A, SAMID D, Cooper MR, Figg WD, Tompkins AC, Patronas N, et al

(1995)

Phase I study of phenylacetate administered twice daily to patients with cancer

Cancer 75(12):2932–2938
http://www.ncbi.nlm.nih.gov/m/pubmed/7773944/
30. Stockhammer G, Manley GT, Johnson R, Rosenblum MK, SAMID D, Lieberman FS

(1995)

Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate

J Neurosurg 83(4):672–681
http://www.ncbi.nlm.nih.gov/m/pubmed/7674018/
32. Ram Z, SAMID D, Walbridge S, Oshiro EM, Viola JJ, Tao-Cheng JH, et al

(1994)

Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate

Cancer Res 54(11):2923–2927
http://www.ncbi.nlm.nih.gov/m/pubmed/8187079/

http://m.cancerres.aacrjournals.org/content/54/11/2923.full.pdf

http://m.cancerres.aacrjournals.org/content/54/11/2923.abstract

http://cancerres.aacrjournals.org/content/54/11/2923
33. SAMID D, Yeh TJ, Shack S

(1991)

Interferon in combination with antitumourigenic phenyl derivatives: potentiation of IFN alpha activity in-vitro

Br J Haematol 79(Suppl 1):81–83
http://www.ncbi.nlm.nih.gov/m/pubmed/1931716/
34. Gorospe M, Shack S, Guyton KZ, SAMID D, Holbrook NJ

(1996)

Up-regulation and functional role of p21Waf1/Cip1 during growth arrest of human breast carcinoma MCF-7 cells by phenylacetate

Cell Growth Differ 7(12):1609–1615
http://www.ncbi.nlm.nih.gov/m/pubmed/8959328/
35. Bar-Ner M, Thibault A, Tsokos M, Magrath IT, SAMID D

(1999)

PHENYLBUTYRATE induces cell differentiation and modulates Epstein-Barr virus gene expression in Burkitt’s lymphoma cells

Clin Cancer Res 5(6):1509–1516
http://www.ncbi.nlm.nih.gov/m/pubmed/10389940/

http://m.clincancerres.aacrjournals.org/content/5/6/1509.abstract

http://m.clincancerres.aacrjournals.org/content/5/6/1509.long

http://clincancerres.aacrjournals.org/content/5/6/1509
36. Shack S, Miller A, Liu L, Prasanna P, Thibault A, SAMID D

(1996)

Vulnerability of multidrug-resistant tumor cells to the aromatic fatty acids phenylacetate and PHENYLBUTYRATE

Clin Cancer Res 2(5):865–872
http://www.ncbi.nlm.nih.gov/m/pubmed/9816242/

http://m.clincancerres.aacrjournals.org/content/2/5/865.abstract

http://m.clincancerres.aacrjournals.org/content/2/5/865.full.pdf

http://clincancerres.aacrjournals.org/content/2/5/865
37. SAMID D, Yeh A, Prasanna P

(1992)

Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate

Blood 80(6):1576–1581
http://www.ncbi.nlm.nih.gov/m/pubmed/1381630/

http://m.bloodjournal.hematologylibrary.org/content/80/6/1576.abstract

http://m.bloodjournal.hematologylibrary.org/content/80/6/1576.full.pdf
38. Fibach E, Prasanna P, Rodgers GP, SAMID D

(1993)

Enhanced fetal hemoglobin production by phenylacetate and 4-PHENYLBUTYRATE in erythroid precursors derived from normal donors and patients with sickle cell anemia and beta-thalassemia

Blood 82(7):2203–2209
http://www.ncbi.nlm.nih.gov/m/pubmed/7691251/

http://m.bloodjournal.hematologylibrary.org/content/82/7/2203.abstract

http://m.bloodjournal.hematologylibrary.org/content/82/7/2203.full.pdf
� � � � � � � � � � � � � � � � �
4/2009Phase 2 study of sodium PHENYLBUTYRATE in ALS.
Merit E Cudkowicz, Patricia L Andres, … THE NORTHEAST ALS AND THE NATIONAL VA ALS RESEARCH CONSORTIUMS
Amyotroph Lateral Scler 10(2):99-106 (2009), PMID.18688762
Amyotroph Lateral Scler. 2009 Apr;10(2):99-106. doi: 10.1080/17482960802320487
http://www.ncbi.nlm.nih.gov/m/pubmed/18688762

http://informahealthcare.com/doi/pdf/10.1080/17482960802320487?noFrame=true

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871887
� � � � � � � � � � � � � � � � �
10/1/2009 – A Phase I Dose-Finding Study of 5-Azacytidine in Combination with Sodium PHENYBUTYRATE in Patients with Refractory Solid Tumors
J Lin, J Gilbert, … M A Carducci
Clin Cancer Res 15(19):6241-6249 (2009), PMID.19789320, PMCID PMC2845396
Clin Cancer Res. 2009 Oct 1;15(19):6241-9. doi: 10.1158/1078-0432.CCR-09-0567. Epub 2009 Sep 29
http://www.ncbi.nlm.nih.gov/m/pubmed/19789320

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845396
References:

24. Robertson KD, Hayward SD, Ling PD, SAMID D, Ambinder RF

Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment:

evidence that demethylation at a single CpG site is crucial

Mol Cell Biol. 1995;15:6150–9
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC230866/
� � � � � � � � � � � � � � � � �
7/2010Phase 2 comparison of a novel ammonia scavenging agent with sodium PHENYLBUTYRATE in patients with urea cycle disorders:

Safety, pharmacokinetics and ammonia control
http://www.ncbi.nlm.nih.gov/m/pubmed/20382058/
Brendan Lee, William Rhead, … Susan A Berry
Mol Genet Metab 100(3):8 (2010), PMID.20382058, PMCID PMC2905228
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905228/
Mol Genet Metab. 2010 Jul;100(3):221-8. doi: 10.1016/j.ymgme.2010.03.014. Epub 2010 Mar 23.
Baylor College of Medicine, Houston, TX, USA.

http://www.sciencedirect.com/science/article/pii/S1096719210001058
a Baylor College of Medicine, Houston, TX, United States
b Howard Hughes Medical Institute, TX, United States
c Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
d Mount Sinai School of Medicine, New York, NY, United States
e Hyperion Therapeutics, Inc., South San Francisco, CA, United States
f Pharsight Corp., Montreal, Quebec, Canada
g Chiltern, Wilmington, NC, United States
h Division of Genetics and Metabolism, University of Minnesota, Minneapolis, MN, United States
http://dx.doi.org/10.1016/j.ymgme.2010.03.014

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