William Parker

Summary

Affiliation: Southern Research Institute
Country: USA

Publications

  1. ncbi request reprint Purine metabolism in Mycobacterium tuberculosis as a target for drug development
    William B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Curr Pharm Des 13:599-608. 2007
  2. ncbi request reprint Lack of mitochondrial toxicity in CEM cells treated with carbovir
    W B Parker
    Kettering Meyer Laboratory, Southern Research Institute, Birmingham, AL 35205, USA
    Antiviral Res 34:131-6. 1997
  3. ncbi request reprint Metabolism and antiviral activity of ribavirin
    William B Parker
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Virus Res 107:165-71. 2005
  4. ncbi request reprint Purine nucleoside antimetabolites in development for the treatment of cancer
    William B Parker
    Southern Research Institute, Birmingham, AL 35255, USA
    Curr Opin Investig Drugs 5:592-6. 2004
  5. ncbi request reprint Metabolism of 2-methyladenosine in Mycobacterium tuberculosis
    William B Parker
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Tuberculosis (Edinb) 84:327-36. 2004
  6. ncbi request reprint Design and evaluation of 5'-modified nucleoside analogs as prodrugs for an E. coli purine nucleoside phosphorylase mutant
    William B Parker
    Southern Research Institute, 2000 Ninth Ave, South, Birmingham, AL 35205, USA
    Nucleosides Nucleotides Nucleic Acids 24:387-92. 2005
  7. pmc Effect of expression of adenine phosphoribosyltransferase on the in vivo anti-tumor activity of prodrugs activated by E. coli purine nucleoside phosphorylase
    W B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Cancer Gene Ther 18:390-8. 2011
  8. ncbi request reprint Antitumor activity of 2-fluoro-2'-deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase
    William B Parker
    Southern Research Institute, Birmingham, Alabama 35205, USA
    Cancer Gene Ther 10:23-9. 2003
  9. ncbi request reprint Comparison of the mechanism of cytotoxicity of 2-chloro-9-(2-deoxy-2- fluoro-beta-D-arabinofuranosyl)adenine, 2-chloro-9-(2-deoxy-2-fluoro- beta-D-ribofuranosyl)adenine, and 2-chloro-9-(2-deoxy-2,2-difluoro- beta-D-ribofuranosyl)adenine in CEM cells
    W B Parker
    Southern Research Institute, Birmingham, Alabama 35205, USA
    Mol Pharmacol 55:515-20. 1999
  10. ncbi request reprint Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human cells
    W B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Biochem Pharmacol 55:1673-81. 1998

Research Grants

  1. PURINE ANALOG ANTIMYCOBACTERIAL DRUG DEVELOPMENT
    William Parker; Fiscal Year: 2001
  2. Purine Analog Anti-Mycobacterial Drug Development
    William Parker; Fiscal Year: 2009

Collaborators

Detail Information

Publications45

  1. ncbi request reprint Purine metabolism in Mycobacterium tuberculosis as a target for drug development
    William B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Curr Pharm Des 13:599-608. 2007
    ..tuberculosis replication. Compounds in this class should be active against strains of M. tuberculosis that are resistant to current agents used to treat this disease and may also target latent disease...
  2. ncbi request reprint Lack of mitochondrial toxicity in CEM cells treated with carbovir
    W B Parker
    Kettering Meyer Laboratory, Southern Research Institute, Birmingham, AL 35205, USA
    Antiviral Res 34:131-6. 1997
    ....
  3. ncbi request reprint Metabolism and antiviral activity of ribavirin
    William B Parker
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Virus Res 107:165-71. 2005
    ..This observation is well known by investigators familiar with nucleoside analogs, but indicate that one should not assume that agents of similar structure have identical activities...
  4. ncbi request reprint Purine nucleoside antimetabolites in development for the treatment of cancer
    William B Parker
    Southern Research Institute, Birmingham, AL 35255, USA
    Curr Opin Investig Drugs 5:592-6. 2004
    ..Even though nucleoside analogs have been extensively evaluated over the last 50 years, the development of these new compounds demonstrates that there is still much promise in identifying new anticancer drugs from this class of compounds...
  5. ncbi request reprint Metabolism of 2-methyladenosine in Mycobacterium tuberculosis
    William B Parker
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Tuberculosis (Edinb) 84:327-36. 2004
    ..tuberculosis. These studies have identified two enzyme reactions (Ado kinase and Ado cleavage) in M. tuberculosis that could be exploited for the rational design of new and selective anti-M. tuberculosis agents...
  6. ncbi request reprint Design and evaluation of 5'-modified nucleoside analogs as prodrugs for an E. coli purine nucleoside phosphorylase mutant
    William B Parker
    Southern Research Institute, 2000 Ninth Ave, South, Birmingham, AL 35205, USA
    Nucleosides Nucleotides Nucleic Acids 24:387-92. 2005
    ....
  7. pmc Effect of expression of adenine phosphoribosyltransferase on the in vivo anti-tumor activity of prodrugs activated by E. coli purine nucleoside phosphorylase
    W B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Cancer Gene Ther 18:390-8. 2011
    ..These results provide insight into the mechanism of bystander killing of the E. coli PNP strategy, and suggest ways to enhance the approach that are independent of APRT...
  8. ncbi request reprint Antitumor activity of 2-fluoro-2'-deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase
    William B Parker
    Southern Research Institute, Birmingham, Alabama 35205, USA
    Cancer Gene Ther 10:23-9. 2003
    ..Regardless, these results indicated that F-dAdo was also an excellent prodrug for use with gene vectors that deliver E. coli PNP to tumor cells...
  9. ncbi request reprint Comparison of the mechanism of cytotoxicity of 2-chloro-9-(2-deoxy-2- fluoro-beta-D-arabinofuranosyl)adenine, 2-chloro-9-(2-deoxy-2-fluoro- beta-D-ribofuranosyl)adenine, and 2-chloro-9-(2-deoxy-2,2-difluoro- beta-D-ribofuranosyl)adenine in CEM cells
    W B Parker
    Southern Research Institute, Birmingham, Alabama 35205, USA
    Mol Pharmacol 55:515-20. 1999
    ....
  10. ncbi request reprint Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human cells
    W B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Biochem Pharmacol 55:1673-81. 1998
    ..coli cytosine deaminase. These advantages include a novel mechanism of action resulting in toxicity to nonproliferating and proliferating tumor cells and the high potency of these agents during short-term treatment...
  11. ncbi request reprint Metabolism of 4'-thio-beta-D-arabinofuranosylcytosine in CEM cells
    W B Parker
    Southern Research Institute, Birmingham, AL 35205, USA
    Biochem Pharmacol 60:1925-32. 2000
    ..The data in this study represent another example of how relatively small structural changes in nucleoside analogs can profoundly affect the biochemical activity...
  12. pmc Adenosine regulation of cystic fibrosis transmembrane conductance regulator through prostenoids in airway epithelia
    Yao Li
    Department of Pediatrics and Physiology and Biophysics, and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham and Southern Research Institute, Birmingham, AL 35233, USA
    Am J Respir Cell Mol Biol 34:600-8. 2006
    ..Together, the results provide a converging mechanism to link regulation of CFTR and airway cell inflammation through adenosine and adenosine receptors...
  13. ncbi request reprint Excellent in vivo bystander activity of fludarabine phosphate against human glioma xenografts that express the escherichia coli purine nucleoside phosphorylase gene
    Jeong S Hong
    Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 0005, USA
    Cancer Res 64:6610-5. 2004
    ..These findings define levels of E. coli PNP expression necessary for antitumor activity with F-araAMP and demonstrate new potential for a clinically approved compound in solid tumor therapy...
  14. ncbi request reprint Tumor sensitization to purine analogs by E. coli PNP
    Kimberly V Curlee
    Department of Human Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
    Methods Mol Med 90:223-45. 2004
  15. doi request reprint Regioselective metalation of 6-methylpurines: synthesis of fluoromethyl purines and related nucleosides for suicide gene therapy of cancer
    Abdalla E A Hassan
    Southern Research Institute, Drug Discovery Division, Birmingham, Alabama, USA
    Nucleosides Nucleotides Nucleic Acids 28:642-56. 2009
    ..The cytotoxic activity of 6-FMeP along with the substrate activity of 6-FMePR with E. coli PNP meet the fundamental requirements for using 6-FMeP as a potential toxin in PNP/prodrug based cancer gene therapy...
  16. ncbi request reprint c-Abl-independent p73 stabilization during gemcitabine- or 4'-thio-beta-D-arabinofuranosylcytosine-induced apoptosis in wild-type and p53-null colorectal cancer cells
    Jaideep V Thottassery
    Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Mol Cancer Ther 5:400-10. 2006
    ..Together, these studies indicate that c-Abl-independent p73 stabilization pathways could account for the p53-independent mechanisms in nucleoside-induced apoptosis...
  17. pmc Identification and characterization of a unique adenosine kinase from Mycobacterium tuberculosis
    Mary C Long
    Southern Research Institute, Birmingham, Alabama 35205, USA
    J Bacteriol 185:6548-55. 2003
    ..The multiple differences that exist between M. tuberculosis and human AKs may provide the molecular basis for the development of nucleoside analog compounds with selective activity against M. tuberculosis...
  18. doi request reprint Synthesis and anticancer evaluation of 4'-C-methyl-2'-fluoro arabino nucleosides
    Kamal N Tiwari
    Southern Research Institute, Drug Discovery Division, Birmingham, Alabama, USA
    Nucleosides Nucleotides Nucleic Acids 28:657-77. 2009
    ..The synthesis and anticancer activity of this series of nucleosides are reported...
  19. doi request reprint Enhancement of the in vivo antitumor activity of clofarabine by 1-beta-D-[4-thio-arabinofuranosyl]-cytosine
    William B Parker
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Cancer Chemother Pharmacol 64:253-61. 2009
    ..Since T-araC has a vastly superior preclinical efficacy profile in comparison to araC, we have initiated studies to determine the potential value of clofarabine/T-araC combination therapy...
  20. ncbi request reprint Long intracellular retention of 4'-thio-arabinofuranosylcytosine 5'-triphosphate as a critical factor for the anti-solid tumor activity of 4'-thio-arabinofuranosylcytosine
    Hitoshi Someya
    Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA
    Cancer Chemother Pharmacol 57:772-80. 2006
    ....
  21. pmc Activity of ribavirin against Hantaan virus correlates with production of ribavirin-5'-triphosphate, not with inhibition of IMP dehydrogenase
    Yanjie Sun
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Antimicrob Agents Chemother 51:84-8. 2007
    ..These results suggest that the inhibition of IMP dehydrogenase by RBV is of secondary importance to the inhibition of vRNA replication by RBV and that the interaction of RBV-TP with the viral polymerase is the primary action of RBV...
  22. ncbi request reprint Evaluation of 3-deaza-adenosine analogues as ligands for adenosine kinase and inhibitors of Mycobacterium tuberculosis growth
    Mary C Long
    Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    J Antimicrob Chemother 59:118-21. 2007
    ..Analyse a series of halogenated 3-deaza-adenosine analogues for efficacy against Mycobacterium tuberculosis H37Ra and determine if adenosine (Ado) kinase plays a role in the mechanism of action of these compounds...
  23. pmc Synthesis of 1-beta-D-ribofuranosyl-3-ethynyl-[1,2,4]triazole and its in vitro and in vivo efficacy against Hantavirus
    DONG HOON CHUNG
    Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, AL 35205, USA
    Antiviral Res 79:19-27. 2008
    ..ETAR is an exciting and promising lead compound that will be elaborated in further synthetic investigations as a framework for the rational design of new antivirals for treatment of HFRS...
  24. ncbi request reprint Phosphorylation of 4'-thio-beta-D-arabinofuranosylcytosine and its analogs by human deoxycytidine kinase
    Hitoshi Someya
    Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, USA
    J Pharmacol Exp Ther 304:1314-22. 2003
    ....
  25. ncbi request reprint Enhancement of nucleoside cytotoxicity through nucleotide prodrugs
    Jerry D Rose
    Southern Research Institute, P O Box 55305, Birmingham, Alabama 35255 5305, USA
    J Med Chem 45:4505-12. 2002
    ..Further cell culture experiments were conducted to gain insight into the mechanisms of cytotoxicity of these two prodrugs, and those data are reported...
  26. ncbi request reprint A long-acting suicide gene toxin, 6-methylpurine, inhibits slow growing tumors after a single administration
    Vijayakrishna K Gadi
    Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
    J Pharmacol Exp Ther 304:1280-4. 2003
    ..The findings also help explain the strong in vivo bystander killing mechanism ascribed by several laboratories to E. coli PNP in the past...
  27. pmc Failure of cAMP agonists to activate rescued deltaF508 CFTR in CFBE41o- airway epithelial monolayers
    Zsuzsa Bebok
    Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
    J Physiol 569:601-15. 2005
    ....
  28. pmc Overexpression, purification and crystallographic analysis of a unique adenosine kinase from Mycobacterium tuberculosis
    Yimin Wang
    Southern Research Institute, Birmingham, Alabama 35205, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 61:553-7. 2005
    ..An understanding of how the M. tuberculosis adenosine kinase differs from the human homolog should aid in the design of more potent and selective antimycobacterial agents that are selectively activated by this enzyme...
  29. ncbi request reprint The metabolism of 2-methyladenosine in Mycobacterium smegmatis
    Chih Kuang Chen
    Biochemistry Department, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Microbiology 148:289-95. 2002
    ..These studies demonstrated the importance of adenosine kinase in the activation of methyl-ado to toxic metabolites in M. smegmatis...
  30. ncbi request reprint Antiangiogenic activity of 4'-thio-beta-D-arabinofuranosylcytosine
    Anshu M Roy
    Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, USA
    Mol Cancer Ther 5:2218-24. 2006
    ..This study also provides important information for optimizing dosage and sequence of T-araC administration in clinical investigations by considering T-araC as both an antiproliferative and an antiangiogenic agent...
  31. ncbi request reprint Selective metalation of 6-methylpurines: synthesis of 6-fluoromethylpurines and related nucleosides
    Abdalla E A Hassan
    Drug Discovery Division, Southern Research Institute, Birmingham, Alabama, USA
    Nucleosides Nucleotides Nucleic Acids 22:747-9. 2003
    ..In the presence of N-fluorobenzenesulfonamide (NFSI), this property was utilized for the synthesis of 6-fluoromethylpurine derivatives 4 and 5 as potential toxins for suicide gene therapy...
  32. pmc Synthesis and anti-Hantaan virus activity of N(1)-3-fluorophenyl-inosine
    DONG HOON CHUNG
    Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, AL 35205, USA
    Antiviral Res 83:80-5. 2009
    ..Synthesis of other compounds structurally similar to FPI is warranted to identify more potent agents that selectively abrogate production of infectious virus...
  33. pmc Ribavirin reveals a lethal threshold of allowable mutation frequency for Hantaan virus
    DONG HOON CHUNG
    Department of Biochemistry and Molecular Biology, 2000 9th Avenue South, Southern Research Institute, Birmingham, AL 35205, USA
    J Virol 81:11722-9. 2007
    ..These studies revealed a lethal threshold, after which we did not observe a complete loss of the quasispecies structure of the wild-type genome, although we observed extinction of HTNV...
  34. ncbi request reprint Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system
    Eric M Bennett
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Chem Biol 10:1173-81. 2003
    ..coli PNP. In a xenograft tumor experiment, this compound caused regression of tumors expressing the M64V PNP gene...
  35. ncbi request reprint Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase
    Eric M Bennett
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA
    J Biol Chem 278:47110-8. 2003
    ....
  36. ncbi request reprint PNP anticancer gene therapy
    Yang Zhang
    Baker Laboratory, Cornell University, Ithaca, NY 14853 1301, USA
    Curr Top Med Chem 5:1259-74. 2005
    ..coli PNP anticancer gene therapy. We also review the structural basis for activity of nucleoside phosphorylases and suggest future directions for the development of activating enzymes for suicide gene therapy...
  37. ncbi request reprint Antibiotic-mediated chemoprotection enhances adaptation of E. coli PNP for herpes simplex virus-based glioma therapy
    Suman Bharara
    Department of Surgery, University of Alabama at Birmingham, AL 35294, USA
    Hum Gene Ther 16:339-47. 2005
    ..Bystander killing of the magnitude described here has been difficult to accomplish with other suicide genes, such as HSV-tk or cytosine deaminase. The results establish a model for applying E. coli PNP to HSV treatment of glioma...
  38. ncbi request reprint Lymphoma chemovirotherapy: CD20-targeted and convertase-armed measles virus can synergize with fludarabine
    Guy Ungerechts
    Molecular Medicine Program and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, Minnesota 55902, USA
    Cancer Res 67:10939-47. 2007
    ..Cells from MCL patients were shown to be sensitive to infection. Thus, synergy of F-araAMP with a PNP-armed and CD20-targeted MV was shown in one lymphoma therapy model after systemic vector inoculation...
  39. pmc Structure-activity relationship for adenosine kinase from Mycobacterium tuberculosis II. Modifications to the ribofuranosyl moiety
    Mary C Long
    Department of Pharmacology and Toxicology, University of Alabama at Birmingham, AL, United States
    Biochem Pharmacol 75:1588-600. 2008
    ..The most potent inhibitor identified, 5'-amino-5'-deoxy-Ado, had a K(i)=0.8muM and a competitive mode of inhibition. MIC studies demonstrated that poor substrates could still have potent antitubercular activity...
  40. ncbi request reprint An immunocompetent murine model for oncolysis with an armed and targeted measles virus
    Guy Ungerechts
    Molecular Medicine Program and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, Minnesota 55902, USA
    Mol Ther 15:1991-7. 2007
    ..This immunocompetent murine model facilitates the testing of therapeutic regimens for clinical trials...
  41. ncbi request reprint Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases
    Joy Y Feng
    Gilead Sciences, 4 University Place, 4611 University Drive, Durham, NC 27707, USA
    Biochem Pharmacol 68:1879-88. 2004
    ..5 nM) of DXG-TP was detected as the primary metabolite. Our study demonstrated that 5'-nucleotidase, GMP kinase, creatine kinase, and NDP kinase could be responsible for the activation of DXG in vivo...
  42. ncbi request reprint Multi-log cytotoxicity of carbocyclic 2'-deoxyguanosine in HSV-TK-expressing human tumor cells
    Donna S Shewach
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Hum Gene Ther 13:543-51. 2002
    ..Thus, CdG is a potent cytotoxic agent that merits further investigation to determine whether it will be therapeutically effective in enzyme-prodrug therapy with HSV-TK...
  43. ncbi request reprint Antimycobacterial activity of 2-methyl-adenosine
    Esther W Barrow
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
    J Antimicrob Chemother 52:801-8. 2003
    ..tuberculosis in a persistent state model and examine its potential mechanism of action...
  44. ncbi request reprint Structure-activity relationship for nucleoside analogs as inhibitors or substrates of adenosine kinase from Mycobacterium tuberculosis. I. Modifications to the adenine moiety
    Mary C Long
    Department of Pharmacology and Toxicology, University of Alabama at Birmingham, AL, United States
    Biochem Pharmacol 71:1671-82. 2006
    ..Future studies will utilize this information for the design of new analogs that may be selective antitubercular agents...
  45. ncbi request reprint Structural effects on the phosphorylation of 3-substituted 1-beta-D-ribofuranosyl-1,2,4-triazoles by human adenosine kinase
    Sidath C Kumarapperuma
    Department of Chemistry and Biochemistry, MSC 3C, New Mexico State University, Las Cruces, NM 88003, USA
    Bioorg Med Chem Lett 17:3203-7. 2007
    ....

Research Grants7

  1. PURINE ANALOG ANTIMYCOBACTERIAL DRUG DEVELOPMENT
    William Parker; Fiscal Year: 2001
    ..tb activity and toxicity. ..
  2. Purine Analog Anti-Mycobacterial Drug Development
    William Parker; Fiscal Year: 2009
    ..tb activity; and (4) design and synthesis of purine and purine nucleoside analogs with selective activity against M. tb. ..