prodrugs

Summary

Summary: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.

Top Publications

  1. ncbi Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles
    Felix Kratz
    Head of Macromolecular Prodrugs, Tumor Biology Center, Breisacher Strasse 117, D 79106 Freiburg, Germany
    J Control Release 132:171-83. 2008
  2. ncbi Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteers
    James Ermer
    Shire Development, 725 Chesterbrook Blvd, Wayne, PA 19087, USA
    J Clin Pharmacol 50:1001-10. 2010
  3. pmc Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies
    Silvia Curado
    Department of Biochemistry and Biophysics, Program in Developmental Biology, Liver Center, Diabetes Center and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158 2324, USA
    Nat Protoc 3:948-54. 2008
  4. ncbi Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse
    D R Jasinski
    Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    J Psychopharmacol 23:419-27. 2009
  5. pmc EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment
    Di Chen
    the Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, USA
    Adv Clin Chem 53:155-77. 2011
  6. ncbi Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran
    Sam Schulman
    Coagulation Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden
    N Engl J Med 349:1713-21. 2003
  7. ncbi Current progress in suicide gene therapy for cancer
    Kazuyuki Yazawa
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Suite 1661, Houston, Texas 77030, USA
    World J Surg 26:783-9. 2002
  8. ncbi Lipid nanoparticles with different oil/fatty ester ratios as carriers of buprenorphine and its prodrugs for injection
    Jhi Joung Wang
    Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
    Eur J Pharm Sci 38:138-46. 2009
  9. ncbi Nitrosothiol esters of diclofenac: synthesis and pharmacological characterization as gastrointestinal-sparing prodrugs
    U K Bandarage
    NitroMed, Inc, 12 Oak Park Drive, Bedford, Massachusetts 01730, USA
    J Med Chem 43:4005-16. 2000
  10. ncbi Genetically engineered stem cells expressing cytosine deaminase and interferon-β migrate to human lung cancer cells and have potentially therapeutic anti-tumor effects
    Bo Rim Yi
    College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361 763, Republic of Korea
    Int J Oncol 39:833-9. 2011

Detail Information

Publications323 found, 100 shown here

  1. ncbi Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles
    Felix Kratz
    Head of Macromolecular Prodrugs, Tumor Biology Center, Breisacher Strasse 117, D 79106 Freiburg, Germany
    J Control Release 132:171-83. 2008
    ....
  2. ncbi Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteers
    James Ermer
    Shire Development, 725 Chesterbrook Blvd, Wayne, PA 19087, USA
    J Clin Pharmacol 50:1001-10. 2010
    ..These findings indicate that the pharmacokinetic parameters of d-amphetamine were dose-proportional and predictable over a wide range of lisdexamfetamine dimesylate doses...
  3. pmc Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies
    Silvia Curado
    Department of Biochemistry and Biophysics, Program in Developmental Biology, Liver Center, Diabetes Center and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158 2324, USA
    Nat Protoc 3:948-54. 2008
    ..Using this protocol, cell ablation can be achieved in 12-72 h, depending on the transgenic line used, and recovery initiates within the following 24 h...
  4. ncbi Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse
    D R Jasinski
    Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    J Psychopharmacol 23:419-27. 2009
    ..Abuse-related liking scores of LDX at a dose corresponding to a 50% higher amphetamine base (LDX 150 mg) were similar to d-amphetamine 40 mg...
  5. pmc EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment
    Di Chen
    the Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, USA
    Adv Clin Chem 53:155-77. 2011
    ..We also discuss the implications of green tea polyphenols in cancer prevention...
  6. ncbi Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran
    Sam Schulman
    Coagulation Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden
    N Engl J Med 349:1713-21. 2003
    ..For many patients with venous thromboembolism, secondary prevention with vitamin K antagonists is not extended beyond six months, since the risk of recurrence may be outweighed by the risk of major bleeding...
  7. ncbi Current progress in suicide gene therapy for cancer
    Kazuyuki Yazawa
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Suite 1661, Houston, Texas 77030, USA
    World J Surg 26:783-9. 2002
    ..Suicide gene therapy strives to deliver genes to the cancer cells, which convert nontoxic prodrugs into active chemotherapeutic agents...
  8. ncbi Lipid nanoparticles with different oil/fatty ester ratios as carriers of buprenorphine and its prodrugs for injection
    Jhi Joung Wang
    Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
    Eur J Pharm Sci 38:138-46. 2009
    ..To improve the release properties and analgesic duration of the drug, ester prodrugs were also incorporated into the nanoparticles for evaluation...
  9. ncbi Nitrosothiol esters of diclofenac: synthesis and pharmacological characterization as gastrointestinal-sparing prodrugs
    U K Bandarage
    NitroMed, Inc, 12 Oak Park Drive, Bedford, Massachusetts 01730, USA
    J Med Chem 43:4005-16. 2000
    ..All S-NO-diclofenac derivatives acted as orally bioavailable prodrugs, producing significant levels of diclofenac in plasma within 15 min after oral administration to mice...
  10. ncbi Genetically engineered stem cells expressing cytosine deaminase and interferon-β migrate to human lung cancer cells and have potentially therapeutic anti-tumor effects
    Bo Rim Yi
    College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361 763, Republic of Korea
    Int J Oncol 39:833-9. 2011
    ..Furthermore, GESTECs expressing fusion genes (i.e., CD and IFN-β) may have a synergic antitumor effect on lung cancer cells...
  11. ncbi Influence of the prodrugs 5-fluorocytosine and CPT-11 on ovarian cancer cells using genetically engineered stem cells: tumor-tropic potential and inhibition of ovarian cancer cell growth
    Ki Yon Kim
    Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Cancer Sci 101:955-62. 2010
    ..have shown that genetically engineered stem cells (GESTECs) to produce suicide enzymes that convert non-toxic prodrugs to toxic metabolites selectively migrate toward tumor sites and reduce tumor growth...
  12. ncbi Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity
    A Reichenberg
    Jomaa Pharmaka GmbH, Giessen, Germany
    Bioorg Med Chem Lett 11:833-5. 2001
    ..b>Prodrugs of FR900098 with increased activity after oral administration were obtained by chemical modification of the ..
  13. ncbi DNA cross-links in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive metabolism, and cytotoxicity
    Rachelle S Singleton
    Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
    Cancer Res 69:3884-91. 2009
    ....
  14. ncbi A phase I trial of PR-104, a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumors
    Michael B Jameson
    Regional Cancer Centre, Waikato Hospital, Private Bag 3200, Hamilton 3240, New Zealand
    Cancer Chemother Pharmacol 65:791-801. 2010
    ..This study was conducted to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and pharmacokinetics (PK) of PR-104 in patients with advanced solid tumors...
  15. ncbi Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review
    M Malet-Martino
    Groupe de RMN Biomédicale, Laboratoire des IMRCP, Universite Paul Sabatier, Toulouse, France
    Oncologist 7:288-323. 2002
    ..The second part is devoted to a review of the literature on three recent prodrugs of 5-FU, i.e...
  16. pmc Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Br J Pharmacol 147:1-11. 2006
    ..Concurrently, famciclovir was developed as an oral formulation of penciclovir. These antiviral 'prodrugs' thus established a principle that has led to many successful drugs including both nucleoside and nucleotide ..
  17. ncbi Prodrugs--from serendipity to rational design
    Kristiina M Huttunen
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P O Box 1627, FI 70211 Kuopio, Finland
    Pharmacol Rev 63:750-71. 2011
    ..b>Prodrugs are inactive, bioreversible derivatives of active drug molecules that must undergo an enzymatic and/or chemical ..
  18. ncbi Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial
    Lars Wallentin
    Uppsala Clinical Research Centre, University Hospital, Uppsala, Sweden
    Lancet 362:789-97. 2003
    ..We aimed to assess the effectiveness of ximelagatran and acetylsalicylic acid for prevention of death, non-fatal myocardial infarction, and severe recurrent ischaemia after a recent myocardial infarction...
  19. ncbi Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity
    Charles F Albright
    Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Mol Cancer Ther 4:751-60. 2005
    Matrix metalloproteinase (MMP)-activated prodrugs were formed by coupling MMP-cleavable peptides to doxorubicin. The resulting conjugates were excellent in vitro substrates for MMP-2, -9, and -14...
  20. pmc Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104
    Juliana Benito
    Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e23108. 2011
    ..These findings suggest to employ hypoxia-activated prodrugs to eliminate leukemia cells within hypoxic niches...
  21. pmc Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art
    Karl Y Hostetler
    Department of Medicine, Division of Infectious Disease, University of California, San Diego, La Jolla, CA 92093 0676, USA
    Antiviral Res 82:A84-98. 2009
    ..The extension to other nucleoside phosphonate antivirals is highlighted, demonstrating that this novel approach can markedly improve the medicinal properties of these drugs...
  22. ncbi Effective drug delivery by PEGylated drug conjugates
    Richard B Greenwald
    Enzon, Inc, 20 Kingsbridge Road, Piscataway, NJ 08854 3969, USA
    Adv Drug Deliv Rev 55:217-50. 2003
    ..Recent novel PEG oligonucleotides and immunoconjugates are also covered. Clinical results of FDA approved PEGylated proteins are also presented...
  23. ncbi Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954
    G A Prosser
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Biochem Pharmacol 79:678-87. 2010
    ..through the use of tumor-tropic gene delivery vectors coupled with systemic administration of otherwise inert prodrugs. Nitroaromatic prodrugs such as CB1954 hold promise for GDEPT as they are readily reduced to potent DNA ..
  24. ncbi Hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamide
    S K Quinney
    Department of Pharmacy Practice, Purdue University, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 313:1011-6. 2005
    ..44 mM). Inhibition of CES2 in the gastrointestinal tract by loperamide may reduce local formation of 5'-DFCR. Both CES1A1 and CES2 are responsible for the activation of capecitabine, whereas CES3 plays little role in 5'-DFCR formation...
  25. ncbi Horseradish peroxidase-mediated gene therapy: choice of prodrugs in oxic and anoxic tumor conditions
    O Greco
    Gray Cancer Institute, P. O. Box 100, Northwood, Middlesex HA6 2JR, United Kingdom
    Mol Cancer Ther 1:151-60. 2001
    ..These results indicate that HRP/IAA represents an effective system for enzyme/prodrug-based anticancer approaches, and further improvements could be achieved by the use of novel IAA derivatives...
  26. ncbi Enzymatic release of antitumor ether lipids by specific phospholipase A2 activation of liposome-forming prodrugs
    Thomas L Andresen
    Department of Chemistry and LiPlasome Pharma A S, Technical University of Denmark, Building 207, DK 2800 Lyngby, Denmark
    J Med Chem 47:1694-703. 2004
    ..Three prodrugs of AELs (proAELs) have been synthesized and four liposome systems, consisting of these proAELs, were investigated ..
  27. ncbi Polymeric prodrugs
    K Hoste
    Department of Organic Chemistry, Ghent University, Krijgslaan 281 S4bis, 9000 Gent, Belgium
    Int J Pharm 277:119-31. 2004
    In 1975 Prof. H. Ringsdorf proposed a model for rational design of polymeric prodrugs [J. Polym. Sci. Symp. 51 (1975) 135]...
  28. ncbi Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers
    D R Jasinski
    Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    J Psychopharmacol 23:410-8. 2009
    ..LDX was well tolerated in this population. In contrast to d-amphetamine, LDX administered intravenously did not produce significant subjective abuse-related liking scores at assessed doses...
  29. ncbi Prodrugs: a challenge for the drug development
    Jolanta B Zawilska
    Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, PL 93 232 Łódź, Poland
    Pharmacol Rep 65:1-14. 2013
    It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo ..
  30. ncbi Design of anticancer prodrugs for reductive activation
    Yu Chen
    Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA
    Med Res Rev 29:29-64. 2009
    Anticancer prodrugs designed to target specifically tumor cells should increase therapeutic effectiveness and decrease systemic side effects in the treatment of cancer...
  31. ncbi Phase I and pharmacokinetic study of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin
    Clemens Unger
    Department Medical Oncology, Tumor Biology Center, Freiburg, Germany
    Clin Cancer Res 13:4858-66. 2007
    ..The purpose of the phase I study was to characterize the toxicity profile of DOXO-EMCH, establish a recommended dose for phase II studies, and assess potential anticancer activity...
  32. ncbi Beta-aminoketones as prodrugs with pH-controlled activation
    Ana Luisa Simplicio
    School of Pharmacy, Trinity College, Dublin 2, Ireland
    Int J Pharm 336:208-14. 2007
    N-Mannich bases have been widely applied as prodrugs of amine drugs...
  33. ncbi The fourth molybdenum containing enzyme mARC: cloning and involvement in the activation of N-hydroxylated prodrugs
    Sanja Gruenewald
    Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, Christian Albrechts University of Kiel, Gutenbergstrasse 76, D 24118 Kiel, Germany
    J Med Chem 51:8173-7. 2008
    ..These substances are amidoxime/N-hydroxyguanidine prodrugs, leading to improved bioavailability compared to the active amidines/guanidines...
  34. ncbi Prodrug strategies to overcome poor water solubility
    Valentino J Stella
    Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA
    Adv Drug Deliv Rev 59:677-94. 2007
    ..strategy is the design of bioreversible, more water-soluble derivatives of the problematic molecule, or prodrugs. This review explores the use of prodrugs to effect improved oral and parenteral delivery of poorly water-soluble ..
  35. ncbi Attention-deficit hyperactivity disorder: recent advances in paediatric pharmacotherapy
    Diane E May
    Department of Psychiatry, University of Nebraska Medical Center, Omaha, Nebraska 68198 5581, USA
    Drugs 70:15-40. 2010
    ..Such recent developments and ongoing study of additional potential pharmacological interventions may lead to additional future treatment options for children with ADHD...
  36. ncbi Liposome-mediated targeting of enzymes to cancer cells for site-specific activation of prodrugs: comparison with the corresponding antibody-enzyme conjugate
    Maria José Fonseca
    Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences UIPS, Utrecht University, Utrecht, The Netherlands
    Pharm Res 20:423-8. 2003
    ..These enzymes are capable of converting relatively nontoxic prodrugs into active cytostatic agents...
  37. pmc Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs
    Harinath Chakrapani
    Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA
    Bioorg Med Chem 16:9764-71. 2008
    Nitric oxide (NO) prodrugs such as O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics...
  38. pmc PDEPT: polymer-directed enzyme prodrug therapy. I. HPMA copolymer-cathepsin B and PK1 as a model combination
    R Satchi
    Centre for Polymer Therapeutics, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WCIN IAX, UK
    Br J Cancer 85:1070-6. 2001
    ..This study proves the concept of PDEPT and further optimisation is warranted...
  39. ncbi Targeted mutagenesis of the Vibrio fischeri flavin reductase FRase I to improve activation of the anticancer prodrug CB1954
    P M Swe
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Biochem Pharmacol 84:775-83. 2012
    ..In a bacteria-delivered model for enzyme prodrug therapy, the engineered FRase I variants were able to kill human colon carcinoma (HCT-116) cells at significantly lower CB1954 concentrations than wild type FRase I or E. coli NfsB...
  40. ncbi Enzyme prodrug therapy designed to target L-methioninase to the tumor vasculature
    Brent D Van Rite
    Bioengineering Center, University of Oklahoma, Norman, USA
    Cancer Lett 301:177-84. 2011
    ..Thus, this new approach appears promising...
  41. ncbi Development of novel bisphosphonate prodrugs of doxorubicin for targeting bone metastases that are cleaved pH dependently or by cathepsin B: synthesis, cleavage properties, and binding properties to hydroxyapatite as well as bone matrix
    Katrin Hochdörffer
    Division of Macromolecular Prodrugs, Tumor Biology Center, Breisacher Strasse 117, 79106 Freiburg, Germany
    J Med Chem 55:7502-15. 2012
    ..Thus, we designed two low-molecular-weight and water-soluble prodrugs which incorporate a bisphosphonate group as a bone targeting ligand, doxorubicin as the anticancer agent, and ..
  42. ncbi Synthesis, hydrolysis studies and phamacodynamic profiles of amide prodrugs of dexibuprofen with amino acids
    Arun Rasheed
    Department of Pharmaceutical Chemistry, Sree Vidyanikethan College of Pharmacy, Sree Sainath Nagar, Tirupati, Andhra Pradesh, India
    J Enzyme Inhib Med Chem 26:688-95. 2011
    The present investigation deals with the synthesis of novel prodrugs of dexibuprofen with amino acids with an aim to achieve potent anti-inflammatory activity and less gastrointestinal toxicity...
  43. pmc Riluzole prodrugs for melanoma and ALS: design, synthesis, and in vitro metabolic profiling
    Mark E McDonnell
    Fox Chase Chemical Diversity Center, Inc, 3805 Old Easton Road, Doylestown, PA 18902, USA
    Bioorg Med Chem 20:5642-8. 2012
    ..of this clearance pathway and uniformly administer riluzole at efficacious exposure levels, several classes of prodrugs of riluzole were designed, synthesized, and evaluated in multiple in vitro stability assays to predict in vivo ..
  44. ncbi Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans--toxicological implications
    Hidetoshi Shindoh
    Pre Clinical Research Department, Research Division, Chugai Pharmaceutical Co, Ltd, Kamakura Research Labs, Kanagawa, Japan
    J Toxicol Sci 36:411-22. 2011
    ....
  45. ncbi Evaluation of in vitro models for screening alkaline phosphatase-mediated bioconversion of phosphate ester prodrugs
    Haodan Yuan
    Department of Pharmacokinetics, Dynamics, and Drug Metabolism, Pfizer Global Research and Development, St Louis Laboratories, Pfizer Inc, St Louis, MO, USA
    Drug Metab Dispos 37:1443-7. 2009
    ..In addition, fosphenytoin and fosfluconazole were used as probe prodrugs to evaluate the models...
  46. pmc Lipophilic prodrugs of FR900098 are antimicrobial against Francisella novicida in vivo and in vitro and show GlpT independent efficacy
    Elizabeth S McKenney
    School of Systems Biology, George Mason University, Manassas, Virginia, USA
    PLoS ONE 7:e38167. 2012
    ..novicida. Thus, we synthesized several FR900098 prodrugs that have lipophilic groups to facilitate their passage through the bacterial cell wall and bypass the ..
  47. ncbi Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, UK
    Curr Top Med Chem 11:2072-84. 2011
    ..The nitroheterocyclic prodrugs nifurtimox and benznidazole, in use against Chagas disease for >40 years, remain the only agents available for ..
  48. ncbi Cathepsin B cleavable novel prodrug Ac-Phe-Lys-PABC-ADM enhances efficacy at reduced toxicity in treating gastric cancer peritoneal carcinomatosis: an experimental study
    Li Hua Shao
    Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, China
    Cancer 118:2986-96. 2012
    ..The authors examined the antitumor effect and toxicities of Ac-Phe-Lys-PABC-ADM against gastric cancer peritoneal carcinomatosis...
  49. ncbi Development of beta-lapachone prodrugs for therapy against human cancer cells with elevated NAD(P)H:quinone oxidoreductase 1 levels
    Kathryn E Reinicke
    Laboratory of Molecular Stress Responses, Case Western Reserve University, Cleveland, OH 44106, USA
    Clin Cancer Res 11:3055-64. 2005
    ..We report the development of mono(arylimino) derivatives of beta-lapachone as potential prodrugs. These derivatives are relatively nontoxic and not substrates for NQO1 when initially diluted in water...
  50. ncbi In vivo cancer gene therapy by adenovirus-mediated transfer of a bifunctional yeast cytosine deaminase/uracil phosphoribosyltransferase fusion gene
    P Erbs
    Transgene S A Strasbourg, France
    Cancer Res 60:3813-22. 2000
    ..These unique properties make of the FCU1/5-FC prodrug activation system a novel and powerful candidate for cancer gene therapy strategies...
  51. pmc Prodrugs of bisthiazolium salts are orally potent antimalarials
    Henri J Vial
    Unité Mixte de Recherche 5539, Centre National de la Recherche Scientifique Université Montpellier II, Case 107, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France
    Proc Natl Acad Sci U S A 101:15458-63. 2004
    We created neutral antimalarial prodrugs that deliver bisthiazolium compounds with antimalarial activity in the nanomolar range. These drugs primarily affect early intraerythrocytic stages through rapid, nonreversible cytotoxicity...
  52. ncbi Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors
    Frederic H Jung
    AstraZeneca, Centre de Recherches, Parc Industriel Pompelle, BP1050, Chemin de Vrilly, 51689 Reims Cedex 2, France
    J Med Chem 49:955-70. 2006
    ....
  53. ncbi Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines
    Suryakant K Niture
    Anticancer Resistance Research Group, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center 1400 Wallace Boulevard, Amarillo, TX 79106, USA
    Carcinogenesis 28:378-89. 2007
    ..The non-toxic cysteine prodrugs, 2-oxothiazolidine-4-carboxylic acid (OTC) and N-acetyl-L-cysteine (NAC), metabolized, respectively by 5-..
  54. pmc Poly(L-histidine)-tagged 5-aminolevulinic acid prodrugs: new photosensitizing precursors of protoporphyrin IX for photodynamic colon cancer therapy
    Renjith P Johnson
    WCU Centre for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan, Korea
    Int J Nanomedicine 7:2497-512. 2012
    ..The application of certain triggers, such as pH, into conventional sensitizers for controllable (1)O(2) release is a promising strategy for tumor-targeted treatment...
  55. pmc Investigation of anticholinergic and non-steroidal anti-inflammatory prodrugs which reduce chemically induced skin inflammation
    Sherri C Young
    Department of Chemistry, Lehigh University, Bethlehem, PA 18015, USA
    J Appl Toxicol 32:135-41. 2012
    ..a continuous effort to develop efficient counter measures against sulfur mustard injuries, several unique NSAID prodrugs have been developed and screened for anti-inflammatory properties...
  56. ncbi Novel antitumor prodrugs designed for activation by matrix metalloproteinases-2 and -9
    Toni Kline
    Seattle Genetics, Bothell, Washington 98021, USA
    Mol Pharm 1:9-22. 2004
    ..Our MMP targeting strategy was to prepare and evaluate two classes of enzyme prodrugs, peptides and sequence-similar peptidomimetics, and determine which would be substrates for the enzymes and thus ..
  57. ncbi Endosomal pH-activatable poly(ethylene oxide)-graft-doxorubicin prodrugs: synthesis, drug release, and biodistribution in tumor-bearing mice
    Lei Zhou
    Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P R China
    Biomacromolecules 12:1460-7. 2011
    Novel poly(ethylene oxide)-graft-doxorubicin (PEO-g-DOX) prodrugs with DOX covalently conjugated to PEO via a pH-sensitive hydrazone bond were developed...
  58. ncbi Maleimide-oligo(ethylene glycol) derivatives of camptothecin as albumin-binding prodrugs: synthesis and antitumor efficacy
    Andre Warnecke
    Tumor Biology Center, Breisacher Strasse 117, 79106 Freiburg, Germany
    Bioconjug Chem 14:377-87. 2003
    In situ binding of thiol-reactive prodrugs to the cysteine-34 position of circulating albumin is a new approach in drug delivery...
  59. ncbi Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid
    Gianfranco Pasut
    Pharmaceutical Sciences Department, University of Padua, Via F Marzolo 5, 35143 Padua, Italy
    J Control Release 127:239-48. 2008
    ..These results are promising and encourage in vivo studies on these conjugates that act as polymeric prodrugs.
  60. ncbi Prodrugs for the treatment of neglected diseases
    Man Chin Chung
    Lapdesf Laboratório de Desenvolvimento de Fármacos, Departamento de Farmacos e Medicamentos, Faculdade de Ciências Farmacêuticas UNESP Rodovia Araraquara Jaú Km 1, 14801 902, Brazil
    Molecules 13:616-77. 2008
    ..The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas' disease (American trypanosomiasis)..
  61. ncbi Intratumoral 5-fluorouracil produced by cytosine deaminase/5-fluorocytosine gene therapy is effective for experimental human glioblastomas
    C Ryan Miller
    Department of Radiation Oncology, Division of Radiation Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Cancer Res 62:773-80. 2002
    ....
  62. ncbi Hypoxia-activated prodrugs in cancer therapy: progress to the clinic
    William A Denny
    Auckland Cancer Society Research Centre, The University of Auckland, New Zealand
    Future Oncol 6:419-28. 2010
    ..Nontoxic prodrugs that generate active species in hypoxic tissue by selective bioreduction have long been explored, and the first ..
  63. ncbi Synthesis of piperazinylalkyl ester prodrugs of ketorolac and their in vitro evaluation for transdermal delivery
    Amjad Qandil
    Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
    Drug Dev Ind Pharm 34:1054-63. 2008
    ..In this work, seven piperazinylalkyl ester prodrugs of ketorolac were synthesized to enhance its skin permeation...
  64. ncbi The selectivty and anti-metastatic activity of oral bioavailable butyric acid prodrugs
    Ada Rephaeli
    Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Beilinson Campus, Petach Tikva, 49100, Israel
    Invest New Drugs 24:383-92. 2006
    Acyloxyalkyl ester prodrugs of histone deacetylase inhibitors, a family of anti-cancer agents, are metabolized intracellularly to acids and aldehyde(s)...
  65. ncbi Dinitroglyceryl and diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of aspirin, indomethacin and ibuprofen: synthesis, biological evaluation and nitric oxide release studies
    Khaled R A Abdellatif
    Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta, Canada
    Bioorg Med Chem Lett 19:3014-8. 2009
    A new group of hybrid nitric oxide (NO) releasing anti-inflammatory (AI) ester prodrugs (NONO-NSAIDs) wherein a 1,3-dinitrooxy-2-propyl (12a-c), or O(2)-acetoxymethyl-1-[2-(methyl)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (14a-c), NO-donor ..
  66. ncbi Piperazinylalkyl prodrugs of naproxen improve in vitro skin permeation
    J Rautio
    Department of Pharmaceutical Chemistry, University of Kuopio, P O Box 1627, FIN 70211, Kuopio, Finland
    Eur J Pharm Sci 11:157-63. 2000
    ..were synthesized and evaluated in vitro for their properties as bioreversible topically administered dermal prodrugs of naproxen...
  67. ncbi In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase
    G A Chung-Faye
    CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK
    Gene Ther 8:1547-54. 2001
    ..In summary, VDEPT for colon cancer utilising AdCDUPRT is more effective than AdCD and the bifunctional CDUPRT gene enables the use of either 5-FC or 5-FU as prodrugs.
  68. ncbi Submicron lipid emulsion as a drug delivery system for nalbuphine and its prodrugs
    Jhi Joung Wang
    Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
    J Control Release 115:140-9. 2006
    ..the submicron lipid emulsion as a potential parenteral drug delivery system for nalbuphine and its ester prodrugs. Submicron emulsions were prepared using egg phospholipid as the main emulsifier, various co-emulsifiers were ..
  69. ncbi A safety study of oral valganciclovir maintenance treatment of cytomegalovirus retinitis
    Jacob Lalezari
    Quest Clinical Research, San Francisco, California 94115, USA
    J Acquir Immune Defic Syndr 30:392-400. 2002
    ..Other than a higher than expected frequency of oral candidiasis (17%), no clinical toxicities or laboratory abnormalities occurred during treatment with valganciclovir that have not been observed during treatment with ganciclovir...
  70. ncbi Optimizing prostate cancer suicide gene therapy using herpes simplex virus thymidine kinase active site variants
    Allan J Pantuck
    Department of Urology, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Hum Gene Ther 13:777-89. 2002
    ..library of HSV thymidine kinase enzyme (TK) active site mutants having different affinities for guanosine analog prodrugs was developed...
  71. ncbi Prodrugs: design and clinical applications
    Jarkko Rautio
    Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI 70211 Kuopio, Finland
    Nat Rev Drug Discov 7:255-70. 2008
    b>Prodrugs are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect...
  72. ncbi The role of hypoxia-activated prodrugs in cancer therapy
    W A Denny
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand
    Lancet Oncol 1:25-9. 2000
    ..Hypoxic cells can be exploited for therapy by non-toxic, hypoxia-activated prodrugs. Conceptually, 'trigger' units in these drugs are selectively activated in hypoxic cells to release or activate a ..
  73. ncbi Paclitaxel delivery systems: the use of amino acid linkers in the conjugation of paclitaxel with carboxymethyldextran to create prodrugs
    Shu ichi Sugahara
    The Second Research Department of Central Technology Laboratory, AsahiKasei Corporation, Fuji, Shizuoka, Japan
    Biol Pharm Bull 25:632-41. 2002
    ....
  74. ncbi The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3
    Christopher P Guise
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Auckland, New Zealand
    Cancer Res 70:1573-84. 2010
    ..AKR1C3 was unable to sensitize cells to 10 other bioreductive prodrugs and was associated with single-agent PR-104 activity across a panel of 9 human tumor xenograft models...
  75. ncbi A calorimetric evaluation of the interaction of amphiphilic prodrugs of idebenone with a biomembrane model
    R Pignatello
    Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Catania, Viale A Doria, 6, I 95125 Catania, Italy
    J Colloid Interface Sci 299:626-35. 2006
    ..The enhanced amphiphilicity of the drug due to the LAA moieties caused more complex interactions with DMPC bilayers, compared to those registered with the native drug or IDE alkanoate esters...
  76. ncbi Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrug
    Jinsong Hu
    Department of Hematology and Immunology Myeloma Center Brussels, Vrije Universiteit Brussel, Belgium
    Blood 116:1524-7. 2010
    ..Our data support that hypoxia-activated treatment with TH-302 provides a potential new treatment option for MM...
  77. ncbi Improving the efficacy of antibody-based cancer therapies
    P Carter
    Immunex, Seattle, Washington 98101, USA
    Nat Rev Cancer 1:118-29. 2001
    ..Although antibodies have yet to achieve the ultimate goal of curing cancer, many innovative approaches stand poised to improve the efficacy of antibody-based therapies...
  78. ncbi Cytochrome P450-activated prodrugs: targeted drug delivery
    Kristiina M Huttunen
    Department of Pharmaceutical Chemistry, University of Kuopio, FI 70211 Kuopio, Finland
    Curr Med Chem 15:2346-65. 2008
    ..Whereas the majority of clinically used drugs are inactivated by CYPs, several prodrugs are bioconverted to their active species by these enzymes...
  79. ncbi Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs
    Maria Laura Immordino
    Dipartimento di Scienza e Tecnologia del Farmaco, Universita di Torino, Via Pietro Giuria 9, 10125 Torino, Italy
    J Control Release 100:331-46. 2004
    ..approaches have been tried to improve the metabolic stability; we synthesized a series of increasingly lipophilic prodrugs of gemcitabine by linking the 4-amino group with valeroyl, heptanoyl, lauroyl and stearoyl linear acyl ..
  80. ncbi The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model
    M K Nyati
    Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109 0010, USA
    Gene Ther 9:844-9. 2002
    ....
  81. ncbi Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus
    J Foloppe
    Transgene SA, 11 rue de Molsheim, Strasbourg Cedex, France
    Gene Ther 15:1361-71. 2008
    ....
  82. pmc Tumour tropism and anti-cancer efficacy of polymer-based doxorubicin prodrugs in the treatment of subcutaneous murine B16F10 melanoma
    L W Seymour
    Institute for Cancer Studies, University of Birmingham School of Medicine, UK
    Br J Cancer 70:636-41. 1994
    ....
  83. ncbi Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodents
    Mar Larrosa
    Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS CSIC, 30100 Campus de Espinardo, Murcia, Spain
    J Med Chem 53:7365-76. 2010
    ..However, its rapid metabolism diminishes its effectiveness in the colon. The design of prodrugs to targeting active molecules to the colon provides an opportunity for therapy of IBDs...
  84. ncbi Combination of cytosine deaminase with uracil phosphoribosyl transferase leads to local and distant bystander effects against RM1 prostate cancer in mice
    Aparajita Khatri
    Oncology Research Centre, Prince of Wales Hospital Clinical School of Medicine, The University of New South Wales, Randwick, NSW 2031, Australia
    J Gene Med 8:1086-96. 2006
    ..The product of the fusion gene, CDUPRT, converts the prodrug, 5-fluorocytosine (5FC), into 5-fluorouracil (5FU) and other cytotoxic metabolites that kill both CDUPRT-expressing and surrounding cells, via a 'bystander effect'...
  85. ncbi L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment
    Antonio Di Stefano
    Department of Drug Sciences, G D Annunzio University, Faculty of Pharmacy, Chieti, Italy
    Curr Pharm Des 17:3482-93. 2011
    ..The goal of this paper is to provide the reader with a critical overview on L-Dopa prodrugs here classified according to the nature of the main chemical modification on L-Dopa backbone that led to the ..
  86. ncbi Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers
    Hong Zhao
    Enzon Pharmaceuticals, Inc, 20 Kingsbridge Road, Piscataway, New Jersey 08854, USA
    Bioconjug Chem 19:849-59. 2008
    ..Among the four conjugates, PEG-Gly-(20)-SN38 (23) has been selected as the lead candidate for further preclinical development...
  87. ncbi Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel
    J M Meerum Terwogt
    The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Anticancer Drugs 12:315-23. 2001
    ..Consequently, the safety profile may differ significantly from standard paclitaxel...
  88. ncbi Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence mutagenesis improve prodrug-mediated tumor cell killing
    M E Black
    Department of Pharmaceutical Sciences, Washington State University, Pullman 99164 6534, USA
    Cancer Res 61:3022-6. 2001
    ....
  89. ncbi Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase
    Andrew A Mortlock
    AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    J Med Chem 50:2213-24. 2007
    ..The prodrugs are comprehensively converted to the des-phosphate form in vivo, and the active species have advantageous ..
  90. ncbi Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing
    Rainer Wiewrodt
    Department of Medicine, Philadelphia, Pennsylvania 19194, USA
    Cancer Gene Ther 10:353-64. 2003
    ..HSV-tk when GCV was administered. The use of adenovirus-mediated gene transfer of both tk mutants dm30-tk and sr39-tk for cancer suicide gene therapy should provide a more effective and safer alternative to wild-type HSV-tk...
  91. pmc Optimized clostridium-directed enzyme prodrug therapy improves the antitumor activity of the novel DNA cross-linking agent PR-104
    Shie Chau Liu
    Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA
    Cancer Res 68:7995-8003. 2008
    ..sporogenes spores in SiHa tumor-bearing mice showed significantly improved antitumor efficacy when combined with either 5-aziridinyl-2,4-dinitrobenzamide (CB1954) or the novel dinitrobenzamide mustard prodrug, PR-104...
  92. ncbi In vitro and in vivo evaluation of polyoxyethylene esters as dermal prodrugs of ketoprofen, naproxen and diclofenac
    F P Bonina
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Catania, Viale A Doria 6, 95125 Catania, Italy
    Eur J Pharm Sci 14:123-34. 2001
    ..ketoprofen (1(a-e)), naproxen (2(a-e)) and diclofenac (3(a-e)) were synthesized and evaluated as potential dermal prodrugs of naproxen, ketoprofen and diclofenac...
  93. ncbi Prodrugs forming high drug loading multifunctional nanocapsules for intracellular cancer drug delivery
    Youqing Shen
    Center for Bionanoengineering and the State Key Laboratory for Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China 310027
    J Am Chem Soc 132:4259-65. 2010
    ..conjugated to a very short oligomer chain of ethylene glycol (OEG), forming amphiphilic phospholipid-mimicking prodrugs, OEG-CPT or OEG-DiCPT...
  94. ncbi Synthesis and study of controlled release of ibuprofen from the new acrylic type polymers
    Mirzaagha Babazadeh
    Department of Applied Chemistry, Islamic Azad University, Tabriz Branch, P O Box 1655, Tabriz, Iran
    Int J Pharm 316:68-73. 2006
    ..The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the hydrophilicity of polymer and the pH of the hydrolysis solution...
  95. ncbi Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations
    Soumyajit Majumdar
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, 64110 2499, USA
    J Ocul Pharmacol Ther 21:463-74. 2005
    The aim of this study was to evaluate a series of dipeptide monoester ganciclovir (GCV) prodrugs with the goal of improving ocular bioavailability of GCV from topical ophthalmic solutions.
  96. ncbi Lessons learned from marketed and investigational prodrugs
    Peter Ettmayer
    Novartis Institute for Biomedical Research, Brunnerstrasse 59, A 1235 Vienna, Austria
    J Med Chem 47:2393-404. 2004
  97. ncbi Acyloxyalkyl ester prodrugs of FR900098 with improved in vivo anti-malarial activity
    Regina Ortmann
    Department für Pharmazie, Ludwig Maximilians Universitat Munchen, Butenandtstrasse 5 13, D 81377, Munchen, Germany
    Bioorg Med Chem Lett 13:2163-6. 2003
    ..b>Prodrugs with increased activity after oral administration were obtained by chemical modification of the phosphonate ..
  98. ncbi Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugs
    Swati S More
    Department of Medicinal Chemistry, Center for Drug Design, Academic Health Center, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Med Chem 51:4581-8. 2008
    ..An account of successful syntheses of these prodrugs along with their transport characteristics and stability determination is discussed.
  99. ncbi Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracil
    H Nakamura
    Division of Surgical Oncology and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 61:5447-52. 2001
    ..Combination oncolysis and prodrug bioactivation leads to significant prolongation of survival in mice with diffuse liver metastases...
  100. pmc Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection
    D B Mendel
    Gilead Sciences, Inc, Foster City, California 94404, USA
    Antimicrob Agents Chemother 42:640-6. 1998
    ..These results indicate that GS 4104 is a novel, orally active antiviral agent with the potential to be used for the prophylaxis and treatment of influenza A and B virus infections...
  101. ncbi Exploiting tumour hypoxia in cancer treatment
    J Martin Brown
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford, California 94305, USA
    Nat Rev Cancer 4:437-47. 2004

Research Grants75

  1. IMPROVING SUICIDE GENES FOR CANCER GENE THERAPY
    Margaret Black; Fiscal Year: 2009
    ..These include a poor Km or binding affinity for prodrugs and toxic side effects associated with the high prodrug doses necessary to elicit tumor response...
  2. Preclinical Development of JS-K, a Novel NO-Generating Prodrug for Cancer
    Paul J Shami; Fiscal Year: 2012
    ..JSK Therapeutics (JSKT) has designed a class of diazeniumdiolate prodrugs that release NO upon interaction with glutathione in a reaction catalyzed by glutathione-S-transferase, which is ..
  3. Microsomal Cytochromes P450 and their Interactions with their Redox Partners
    Lucy A Waskell; Fiscal Year: 2013
    ..the human cyts P450 participate, as well as in designing less toxic and more specific therapeutic agents and prodrugs, especially chemotherapeutic agents and environmental contaminants...
  4. CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGS
    Stephen J Lippard; Fiscal Year: 2013
    ..Carbon nanotubes and biodegradable nanoparticles are devised to deliver platinum prodrugs selectively to cancer cells, targeting specific receptors...
  5. Novel Mitochondrial Targeted Neuroprotectants for Glaucoma
    Leonard Levin; Fiscal Year: 2009
    ..Specifically, we plan to: 1. Produce protected phosphine derivatives modified to cross cell membranes, act as prodrugs, and target RGCs. 2...
  6. A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of Nucleoside
    John K Buolamwini; Fiscal Year: 2013
    ..we will test that hypothesis by pursuing the following specific aims: 1) synthesize and characterize novel prodrugs for lack of NT inhibition and cellular release of active drug, 2) evaluate the abiliy of prodrugs to protect ..
  7. Transscleral Transport & Polymeric Delivery of Antibody & Steroids for Macular Ed
    Ashim K Mitra; Fiscal Year: 2010
    ..We propose to combine the prodrug approach with a novel polymeric drug delivery strategy by incorporating these prodrugs into biodegradable surface modified PLGA nanoparticles and thermosensitive PLGA-PEG-PLGA gel...
  8. Tumor drug delivery systems based on polymalic acid
    Julia Y Ljubimova; Fiscal Year: 2010
    ..and the structure of different Polycefin variants, in particular, the number and specificity of conjugated prodrugs (antisense oligonucleotides) and tumor-targeting moieties will be evaluated in vitro and in vivo...
  9. Participation in Cytochrome b5 in Anesthetic Metabolism
    Lucy A Waskell; Fiscal Year: 2010
    ..studies will prove to be extremely valuable in designing less toxic and more specific therapeutic agents and prodrugs, especially chemotherapeutic agents and environmental contaminants...
  10. Rigid-rod Peptides as Nanocarriers for Delivery of Cancer Drugs
    Katarzyna Slowinska; Fiscal Year: 2013
    ..Therefore several prodrugs, typically containing PTX conjugated with the hydrophilic and hydrolyzable groups such as polycarboxylic acids, ..
  11. CHEMOPREVENTION OF SKIN CANCER PROGRAM PROJECT
    George Timothy Bowden; Fiscal Year: 2013
    ..AK) and in situ squamous cell carcinoma (SCIS);3) the selection of novel chemopreventive agents and synthesis of prodrugs that specifically "hit" these molecular targets in SCC and melanoma mouse models and definitively interrupt their ..
  12. AID-mediated genetic instability in BCR-ABL1-transformed B cell lineage leukemia
    MARKUS MUSCHEN; Fiscal Year: 2013
    ..We hypothesize that AID can likewise activate the monomeric prodrugs monomeric 5-FC (Ancobon(R)) and its derivatives 5-DFCR and Capecitabine (Xeloda(R)) into the cytotoxic metabolite ..
  13. Inhibition of Carboxylesterase Metabolism by Ethanol
    Robert B Parker; Fiscal Year: 2011
    ..respectively, where they participate in two reactions important for drug metabolism - the conversion of ester prodrugs to active metabolites and the hydrolysis of active drugs to inactive moieties...
  14. Structural Biology of the Apical Bile Acid Transporter.
    Peter W Swaan; Fiscal Year: 2012
    ..the development of a functional three- dimensional model for human ASBT which can be used in the rational design of novel therapeutics aimed at lowering plasma cholesterol levels or prodrugs designed for enhanced intestinal permeability.
  15. DNA Pro-Drug Technology in Localized Wound Healing and Tissue Regeneration
    Arthur A Decarlo; Fiscal Year: 2011
    ....
  16. SPORE IN PROSTATE CANCER
    WILLIAM GEORGE NELSON; Fiscal Year: 2013
    ..The Research Projects are supported by an Administrative Core (A), which also manages inter-SPORE collaborations, a Tissue Archive Core (B), and a Biostatistics and Epidemiology Core (C). ..
  17. Transmucosal Intra-Oral Drug Delivery System for THC
    Mahmoud A ElSohly; Fiscal Year: 2010
    ..Therefore, different prodrugs will be synthesized during Phase II and evaluated for the selection of the best prodrug/formulation(s) based on ..
  18. Development of Novel Inducers of Non-Apoptotic Cell Death to Target Glioblastoma
    William A Maltese; Fiscal Year: 2013
    ..of the molecular targets of MOMIPP and the development of nanoparticle (NP) delivery vehicles and/or targeted prodrugs that can be used to direct the compound specifically to GBM...
  19. Using vitamin D glucuronide pro-drugs to prevent/treat colon cancer
    JESSE PAUL GOFF; Fiscal Year: 2013
    ..The strength of the current proposal is the ability to target delivery of high concentrations of 1,25- dihydroxyvitamin D3 directly to the colon so its effects on colon carcinogenesis can be assessed in the absence of hypercalcemia. ..
  20. Transdermal delivery of 2-Arachidonoyl glycerol (2-AG) for the treatment of arthr
    Audra L Stinchcomb; Fiscal Year: 2012
    ..We aim to synthesize hydrophilic prodrugs of 2-AG to improve permeation across the skin into synovial fluid...
  21. Tailor-made variants of site-specific recombinases as tools for genome engineerin
    Yuri Voziyanov; Fiscal Year: 2012
    ..The transfected cells will be then treated with prodrugs, which will be converted into toxic products by enzymes coded by the suicide genes...
  22. Development of Novel Class of Anti-Inflammatory Drugs
    KEN CARTER; Fiscal Year: 2013
    ..The technology will address the overlying health problem with patients suffering with IBD and will provide a significant commercialization potential estimated to be over $800M. ..
  23. Combination Therapy With 5-FU and PDT For The Treatment Of Post-Transplant Premal
    Edward V Maytin; Fiscal Year: 2012
    ..Photodynamic therapy (PDT) is a modality that combines topical prodrugs, either aminolevulinic acid (ALA) or its methyl ester (mALA), which are selectively taken up by tumor cells and ..
  24. Use of Beta-Lapachone for Lung Cancer Chemotherapy
    David A Boothman; Fiscal Year: 2013
    ..Previously, we generated nanoparticle micelles that efficaciously delivered ss-lap or ss-lap prodrugs to NSCLCs vs normal tissue, resulting in antitumor responses with significant 'apparent cures'in ..
  25. Transdermal Cannabidiol Prodrug Delivery
    Audra L Stinchcomb; Fiscal Year: 2011
    ..In the first step towards this goal, a proof of concept evaluation of CBD prodrugs delivered via transdermal microneedles will be conducted...
  26. New treatment for androgen sensitive and resistant prostate cancer
    Angela M Brodie; Fiscal Year: 2013
    ....
  27. Estrogen-Derived Para-Quinol Intervention in Alzheimer's Disease
    Mary A Ottinger; Fiscal Year: 2010
    ..We propose to test novel compounds that are classified according to their mechanism of action as prodrugs of endogenous estrogens in a murine model of AD...
  28. Imaging of Cardiac Transplant Rejection
    Matthias Nahrendorf; Fiscal Year: 2013
    ..Specifically, we will validate a) nanoparticles as reporters of phagocytic activity, b) optical prodrugs as sensors of cysteine protease activity, and c) myeloperoxidase-targeted magnetic resonance imaging agents...
  29. Genetic Variants of Human Carboxylesterase 1 Influence the Activation and Antivir
    John S Markowitz; Fiscal Year: 2012
    ..hydrolysis typically results in drug deactivation yet alternatively, it serves to activate many ester-based prodrugs, which include but not limited to oseltamivir (Tamiflu(R)), trandolapril, imidapril, cilazapril, enalapril, ..
  30. Therapeutics Targeting Macrophages/Microglia to Eradicate CNS HIV-1 Reservoirs
    William R Tyor; Fiscal Year: 2013
    ..state of MPs and that can reduce inflammation, MP-specific ribonucleoside chain terminators and their phosphate prodrugs for increased delivery to the CNS, and NADPH oxidase inhibitors that are known to cross the BBB which indirectly ..
  31. Optimization of pyrimidinyl prodrugs (PYPs) for malaria chemotherapy
    PRADIPSINH RATHOD; Fiscal Year: 2009
    yrimidinyl Prodrugs for Malaria Significance: Malaria parasites infect about a billion individuals and cause up to 2 million deaths per year...
  32. SYNTHESIS AND BIOTRANSFORMATION OF ANTI-HIV PRODRUGS
    Chung K Chu; Fiscal Year: 2010
    ..potency, bioavailability, and selective targeted delivery to the lymphatic system and brain, we propose several prodrugs of DAPD...
  33. Prodrugs of NAAG Peptidase Inhibitors for the Treatment of Schizophrenia
    Jia Zhou; Fiscal Year: 2009
    ..The development of prodrugs will provide the means for precise dose delivery to the brain to improve their efficacy as well as the use of ..
  34. HER2-targeted exosomal delivery of therapeutic mRNA for enzyme pro-drug therapy
    AC MATIN; Fiscal Year: 2013
    ..body's "natural antigen delivery system," in order to enhance their natural capacity to activate reductive prodrugs and attach to their surface ligands that specifically target HER2-positive breast cancer, many cases of which are ..
  35. Hypoxia-Selective Kinase Inhibitors for Leukemia Therapy
    Marina Y Konopleva; Fiscal Year: 2013
    ..We will synthesise nitromethylaryl quaternary ammonium salt (NMQ) prodrugs of the known FLT3 inhibitors AC220, MLN-518, sunitinib and crenolanib...
  36. Nitogen reduction and xenobiotic response
    Lauren A Trepanier; Fiscal Year: 2010
    ..The ultimate goal of these studies is to find better ways to prevent these adverse reactions. ..
  37. Boronated nucleosides for neutron capture therapy of brain tumors
    Werner Tjarks; Fiscal Year: 2013
    ..assays with TK1, and to determine their physicochemical properties, (2) to synthesize water-soluble amino acid prodrugs of N5-2OH and to evaluate their applicability for i.c...
  38. Development of a Novel Semen-Activated Prodrug as an Anti-HIV Microbicide
    ROBERT WALTER BUCKHEIT; Fiscal Year: 2010
    ..In the R21 phase of this proposal we propose to develop new microbicides composed of polymeric prodrugs for delivery of the SAMTs...
  39. Transdermal Cannabinoid Prodrug Treatment for Cannabis Withdrawal and Dependence
    Lynn Webster; Fiscal Year: 2010
    ..Initial positive preliminary data has encouraged AllTranz to seek funding to develop new THC prodrugs and optimize their use through a transdermal drug delivery system...
  40. NALTREXONE PRODRUGS FOR TRANSDERMAL DELIVERY
    Audra L Stinchcomb; Fiscal Year: 2010
    ..We plan to continue designing and synthesizing prodrugs, which are more skin permeable than naltrexone, in order to make a therapeutically successful drug delivery ..
  41. Broad Spectrum Antiviral Nucleoside Phosphonate Analogs
    John M Hilfinger; Fiscal Year: 2013
    ..Application of this platform has resulted in prodrugs showing markedly enhanced oral bioavailability, but also significantly greater potency than the parent ANP ..
  42. Using FAP to Selectively Target Epithelial Cancers
    William W Bachovchin; Fiscal Year: 2013
    ..The proposed research will address basic questions about the functions of FAP in tumor progression and support the long-term goal of developing a FAP-targeted pharmacological approach to cancer treatment. ..
  43. Role and Relevance of Pept1 in Drug Absorption, Disposition, and Dynamics
    David E Smith; Fiscal Year: 2013
    ..g., ?-lactam antibiotics, angiotensin-converting enzyme inhibitors, antiviral nucleoside prodrugs) and potentially toxic peptidomimetics (e.g., 5-aminolevulinic acid). However, other members of the POT family (i...
  44. Glutathione S-Transferases in Drug and Stress Response
    Kenneth D Tew; Fiscal Year: 2013
    ..to define mechanism(s) of action for a series of nitric oxide (NO) releasing, GSTP activated diazeniumdiolate prodrugs. Structure activity analyses will determine which metabolites of these drugs may act as proximal donors in the S-..
  45. Selection of the Optimal Nucleoside Triphosphate Mimic Prodrug Inhibitor of HCV R
    PHILLIP DAN COOK; Fiscal Year: 2011
    ..Currently, after the failure of several nucleosides and nucleoside prodrugs in HCV clinical trials, five nucleoside monophosphate prodrugs that target the NS5B polymerase are in HCV ..
  46. Structure/function studies of nucleoside analog activating enzymes
    Arnon Lavie; Fiscal Year: 2009
    Nucleoside analogs (NAs) - a mainstay of anticancer therapy - are prodrugs that upon conversion into their phosphorylated form mimic naturally occurring nucleotides...
  47. Riluzole Prodrugs for Melanoma and ALS
    ALLEN BERNARD REITZ; Fiscal Year: 2013
    ..formulation, analytical methods development, drug substance stability testing, evaluation of additional riluzole prodrugs for added patent protection, as back-ups, and for possible consideration for additional indications, continued ..
  48. Development of JS-K as an anti-leukemic agent
    Paul J Shami; Fiscal Year: 2012
    ..We have designed a class of diazeniumdiolate prodrugs that release NO upon interaction with glutathione in a reaction catalyzed by GST...
  49. Inhibition of the Nonmevalonate pathway to Kill Mycobacterium tuberculosis
    CYNTHIA SCHIECK DOWD; Fiscal Year: 2010
    ..Dxr inhibitor development will be based on two approaches: (I) synthesis of lipophilic prodrugs and bioisosteres to enhance cell penetration and (II) structure-based design of Dxr inhibitors using the recent ..
  50. Meropenem Prodrugs for XDR-TB
    Rory P Remmel; Fiscal Year: 2013
    ..The objectives of this application are to synthesize prodrugs of meropenem that are orally bioavailable...
  51. Targeting hypoxic microenvironment in Acute Lymphocytic Leukemia
    Marina Y Konopleva; Fiscal Year: 2013
    ....
  52. Harnessing ectonucleotidases to treat chronic pain
    Mark J Zylka; Fiscal Year: 2013
    ..In addition, we will use medicinal chemistry to synthesize adenosine prodrugs that can be converted into potent A1-adenosine receptor agonists by ectonucleotidases...
  53. UPLC with Tandem MS for Sensitive Quantitative Analysis of Small Molecules
    Michelle A Rudek; Fiscal Year: 2010
    ..g., preclinical development of thapsigargin prodrugs (R01), agents in Caseating Granulomas (R01), and agents in Buruli ulcers (R01))...
  54. Synthesis and discovery of biologically active cell-permeable cyclic peptides
    R Scott Lokey; Fiscal Year: 2012
    ..we will develop a strategy for the sulfenylation of cyclic and linear peptides, generating bioreversible prodrugs with greatly improved membrane permeability relative to their unmodified parent compounds...
  55. Development of New Beta-Lactamase Inhibitors for Resistant Category B Food/Water-
    CHRISTOPHER JOHN BURNS; Fiscal Year: 2012
    ..an orally bioavailable beta-lactamase inhibitor through synthesis and testing of analogues of PZ-7475 and ester prodrugs thereof...
  56. In vitro detection of anti-TB liver metabolites in early drug discovery
    Scott G Franzblau; Fiscal Year: 2013
    ..Compounds that would only be active after metabolism in the liver (prodrugs) are not detected in high throughput screens...
  57. Role of a Novel Absorption Mechanism in Metformin Disposition and Pharmacology
    Dhiren R Thakker; Fiscal Year: 2013
    ..Metformin analogs or prodrugs with improved therapeutic profile can be conceived based on the findings of this research
  58. DNA Repair in Cancer Biology and Therapy
    Peter M Glazer; Fiscal Year: 2012
    ..Dr. Sartorelli will develop novel hypoxia-activated prodrugs that are designed to inhibit the repair factor, O6-alkylguanine-DNA alkyltransferase (AGT), as well as prodrugs ..
  59. Rational Design of NRTI for Drug Resistant HIV-1
    John W Mellors; Fiscal Year: 2010
    ..In Aim 1, we will synthesize additional, novel ADP analogs, and prodrugs thereof, to optimize potency against both wild-type and NRTI-resistant HIV-1...
  60. Transcleral Therapeutics in Diabetic Retinopathy
    Uday B Kompella; Fiscal Year: 2013
    ..that transscleral retinal delivery and efficacy of highly lipophilic drugs can be enhanced by their polar prodrugs with reduced pigment binding...
  61. Nanoscale Metal-organic Frameworks for Imaging and Therapy of Pancreatic Cancer
    Jen Jen Yeh; Fiscal Year: 2013
    ..The proposed NMOFs contain metal ions or complexes as the MRI imaging cargo and cisplatin or/and Gemcitabine prodrugs as the therapeutic cargoes...
  62. A Silicate Prodrug Strategy for Enhancing Nanoparticle Delivery of Taxanes
    CHRIS MACOSKO; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Hypothesis: Silicate prodrugs of taxane antitumor agents, customized to have proper hydrophobicity and hydrolytic lability, can be formulated with amphiphilic block copolymers into nanoparticles that ..
  63. Genetic and Chemically Programmed Nanoparticles for Prodrug Therapy
    M G Finn; Fiscal Year: 2013
    ..The enzymes on the inside can convert benign prodrugs to cytotoxic agents with high catalytic efficiency, while being protected from protease attack and denaturation...
  64. Ocular Disposition of Antimicrobial Agents
    Ashim K Mitra; Fiscal Year: 2010
    ..We also propose to synthesize amino acid, peptide and ascorbate ester prodrugs of erythromycin, levofloxacin and ofloxacin and ascorbate ester prodrugs of ACV, targeted towards the respective ..
  65. ANTI-AIDS NUCLEOSIDE CONJUGATES OF ETHER PHOSPHOLIPIDS
    CHUNG HONG; Fiscal Year: 1992
    ..Since the proposed prodrugs are conjugates of two biologically active moieties (nucleoside and ether lipid), the improved therapeutic effects ..
  66. AZIDE TECHNOLOGY FOR DRUG DEVELOPMENT
    Kyoichi Watanabe; Fiscal Year: 2001
    ..In Phase I, we will synthesize three new 6-azidopurine derivatives as prodrugs of clinically used antiviral agents, Acyclovir, ganciclovir and penciclovir, and three novel nucleosides ..
  67. Vidarabine Prodrugs as Anti-Pox Virus Agents
    John Hilfinger; Fiscal Year: 2007
    ..The prodrug approach recently has been an effective strategy as demonstrated by the recent success of antiviral prodrugs such as adefovir dipivoxil, famciclovir, tenofovir disoproxil, valacyclovir, and valganciclovir...
  68. A Controlled Trial of NAC for Cocaine Dependence
    Robert Malcolm; Fiscal Year: 2009
    ..placebo;and 3) to study cocaine craving/cue reactivity and withdrawal symptoms in subjects taking NAC or placebo. ..
  69. NAAG Peptidase Inhibitors for the Treatment of Traumatic Brain Injury
    Jia Zhou; Fiscal Year: 2009
    ..The development of prodrugs will provide the means for precise dose delivery to the brain as well as the use of lower dose ranges that ..
  70. Transgenic porphyric Leishmania as suicidal live vaccines against leishmaniasis
    Kwang Poo Chang; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  71. Improving Absorption and Targeting of Antiviral Drugs
    John Hilfinger; Fiscal Year: 2009
    ..for biodefense is to improve the oral absorption of potent, but poorly absorbed anti-pox agents by designing prodrugs targeted to transporters expressed in human intestine and able to be activated by endogenous esterases or ..
  72. Type I Diabetes Model in Zebrafish
    Meera Saxena; Fiscal Year: 2009
    ..Insights gained from generating a diabetes model will help indentify drugs capable of safely stimulating the production of new insulin-producing beta cells - a potential cure for this debilitating disease. ..
  73. CYCLIC PRODRUGS OF OPIOID PEPTIDES
    RONALD BORCHARDT; Fiscal Year: 2007
    ..With support from this NIDA grant, we have designed and synthesized esterase-sensitive cyclic prodrugs of a model opioid peptide (DADLE) that exhibit physicochemical properties (hydrophobicity, low hydrogen bonding ..
  74. MULTIFUNCTIONAL PHOSPHONOFORMATE PRODRUGS AGAINST HIV 1
    Andre Rosowsky; Fiscal Year: 1993
    ..Compounds showing enough activity in vitro will be resynthesized for in vivo testing by Dr. Ruprecht as part of her active work on new anti-AIDS drugs in relevant murine models such as HIV-1 infected chimeric SCID mice...
  75. Development of Anticancer 1,2-Bis(sulfonyl)hydrazines
    Alan Sartorelli; Fiscal Year: 2009
    ..Our laboratory has designed and synthesized a new class of tumor inhibitory prodrugs, the 1,2-bis(sulfonyl) hydrazines, which generate through activation reactive electrophilic structures that cross-..