Genomes and Genes
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.
Publications323 found, 100 shown here
- Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticlesFelix Kratz
Head of Macromolecular Prodrugs, Tumor Biology Center, Breisacher Strasse 117, D 79106 Freiburg, Germany
J Control Release 132:171-83. 2008....
- Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteersJames 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...
- Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studiesSilvia 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...
- Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuseD 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...
- EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatmentDi 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...
- Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatranSam 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...
- Current progress in suicide gene therapy for cancerKazuyuki 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...
- Lipid nanoparticles with different oil/fatty ester ratios as carriers of buprenorphine and its prodrugs for injectionJhi 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...
- Nitrosothiol esters of diclofenac: synthesis and pharmacological characterization as gastrointestinal-sparing prodrugsU 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...
- Genetically engineered stem cells expressing cytosine deaminase and interferon-β migrate to human lung cancer cells and have potentially therapeutic anti-tumor effectsBo 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...
- 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 growthKi 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...
- Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activityA 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 ..
- DNA cross-links in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive metabolism, and cytotoxicityRachelle S Singleton
Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
Cancer Res 69:3884-91. 2009....
- A phase I trial of PR-104, a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumorsMichael 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...
- Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a reviewM 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...
- Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapyErik 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 ..
- Prodrugs--from serendipity to rational designKristiina 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 ..
- Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trialLars 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...
- Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicityCharles F Albright
Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
Mol Cancer Ther 4:751-60. 2005Matrix 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...
- Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104Juliana 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...
- Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the artKarl 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...
- Effective drug delivery by PEGylated drug conjugatesRichard 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...
- Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954G 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 ..
- Hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamideS 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...
- Horseradish peroxidase-mediated gene therapy: choice of prodrugs in oxic and anoxic tumor conditionsO 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...
- Enzymatic release of antitumor ether lipids by specific phospholipase A2 activation of liposome-forming prodrugsThomas 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 ..
- Polymeric prodrugsK Hoste
Department of Organic Chemistry, Ghent University, Krijgslaan 281 S4bis, 9000 Gent, Belgium
Int J Pharm 277:119-31. 2004In 1975 Prof. H. Ringsdorf proposed a model for rational design of polymeric prodrugs [J. Polym. Sci. Symp. 51 (1975) 135]...
- Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusersD 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...
- Prodrugs: a challenge for the drug developmentJolanta B Zawilska
Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, PL 93 232 Łódź, Poland
Pharmacol Rep 65:1-14. 2013It 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 ..
- Design of anticancer prodrugs for reductive activationYu 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. 2009Anticancer prodrugs designed to target specifically tumor cells should increase therapeutic effectiveness and decrease systemic side effects in the treatment of cancer...
- Phase I and pharmacokinetic study of the (6-maleimidocaproyl)hydrazone derivative of doxorubicinClemens 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...
- Beta-aminoketones as prodrugs with pH-controlled activationAna Luisa Simplicio
School of Pharmacy, Trinity College, Dublin 2, Ireland
Int J Pharm 336:208-14. 2007N-Mannich bases have been widely applied as prodrugs of amine drugs...
- The fourth molybdenum containing enzyme mARC: cloning and involvement in the activation of N-hydroxylated prodrugsSanja 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...
- Prodrug strategies to overcome poor water solubilityValentino 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 ..
- Attention-deficit hyperactivity disorder: recent advances in paediatric pharmacotherapyDiane 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...
- Liposome-mediated targeting of enzymes to cancer cells for site-specific activation of prodrugs: comparison with the corresponding antibody-enzyme conjugateMaria 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...
- Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugsHarinath Chakrapani
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA
Bioorg Med Chem 16:9764-71. 2008Nitric 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...
- PDEPT: polymer-directed enzyme prodrug therapy. I. HPMA copolymer-cathepsin B and PK1 as a model combinationR 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...
- Targeted mutagenesis of the Vibrio fischeri flavin reductase FRase I to improve activation of the anticancer prodrug CB1954P 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...
- Enzyme prodrug therapy designed to target L-methioninase to the tumor vasculatureBrent D Van Rite
Bioengineering Center, University of Oklahoma, Norman, USA
Cancer Lett 301:177-84. 2011..Thus, this new approach appears promising...
- 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 matrixKatrin 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 ..
- Synthesis, hydrolysis studies and phamacodynamic profiles of amide prodrugs of dexibuprofen with amino acidsArun 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. 2011The 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...
- Riluzole prodrugs for melanoma and ALS: design, synthesis, and in vitro metabolic profilingMark 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 ..
- Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans--toxicological implicationsHidetoshi Shindoh
Pre Clinical Research Department, Research Division, Chugai Pharmaceutical Co, Ltd, Kamakura Research Labs, Kanagawa, Japan
J Toxicol Sci 36:411-22. 2011....
- Evaluation of in vitro models for screening alkaline phosphatase-mediated bioconversion of phosphate ester prodrugsHaodan 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...
- Lipophilic prodrugs of FR900098 are antimicrobial against Francisella novicida in vivo and in vitro and show GlpT independent efficacyElizabeth 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 ..
- Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectivesShane 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 ..
- Cathepsin B cleavable novel prodrug Ac-Phe-Lys-PABC-ADM enhances efficacy at reduced toxicity in treating gastric cancer peritoneal carcinomatosis: an experimental studyLi 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...
- Development of beta-lapachone prodrugs for therapy against human cancer cells with elevated NAD(P)H:quinone oxidoreductase 1 levelsKathryn 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...
- In vivo cancer gene therapy by adenovirus-mediated transfer of a bifunctional yeast cytosine deaminase/uracil phosphoribosyltransferase fusion geneP 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...
- Prodrugs of bisthiazolium salts are orally potent antimalarialsHenri 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. 2004We 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...
- Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitorsFrederic 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....
- Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell linesSuryakant 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-..
- Poly(L-histidine)-tagged 5-aminolevulinic acid prodrugs: new photosensitizing precursors of protoporphyrin IX for photodynamic colon cancer therapyRenjith 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...
- Investigation of anticholinergic and non-steroidal anti-inflammatory prodrugs which reduce chemically induced skin inflammationSherri 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...
- Novel antitumor prodrugs designed for activation by matrix metalloproteinases-2 and -9Toni 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 ..
- Endosomal pH-activatable poly(ethylene oxide)-graft-doxorubicin prodrugs: synthesis, drug release, and biodistribution in tumor-bearing miceLei 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. 2011Novel poly(ethylene oxide)-graft-doxorubicin (PEO-g-DOX) prodrugs with DOX covalently conjugated to PEO via a pH-sensitive hydrazone bond were developed...
- Maleimide-oligo(ethylene glycol) derivatives of camptothecin as albumin-binding prodrugs: synthesis and antitumor efficacyAndre Warnecke
Tumor Biology Center, Breisacher Strasse 117, 79106 Freiburg, Germany
Bioconjug Chem 14:377-87. 2003In situ binding of thiol-reactive prodrugs to the cysteine-34 position of circulating albumin is a new approach in drug delivery...
- Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acidGianfranco 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.
- Prodrugs for the treatment of neglected diseasesMan 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)..
- Intratumoral 5-fluorouracil produced by cytosine deaminase/5-fluorocytosine gene therapy is effective for experimental human glioblastomasC 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....
- Hypoxia-activated prodrugs in cancer therapy: progress to the clinicWilliam 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 ..
- Synthesis of piperazinylalkyl ester prodrugs of ketorolac and their in vitro evaluation for transdermal deliveryAmjad 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...
- The selectivty and anti-metastatic activity of oral bioavailable butyric acid prodrugsAda Rephaeli
Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Beilinson Campus, Petach Tikva, 49100, Israel
Invest New Drugs 24:383-92. 2006Acyloxyalkyl ester prodrugs of histone deacetylase inhibitors, a family of anti-cancer agents, are metabolized intracellularly to acids and aldehyde(s)...
- 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 studiesKhaled R A Abdellatif
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta, Canada
Bioorg Med Chem Lett 19:3014-8. 2009A 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 ..
- Piperazinylalkyl prodrugs of naproxen improve in vitro skin permeationJ 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...
- In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferaseG 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.
- Submicron lipid emulsion as a drug delivery system for nalbuphine and its prodrugsJhi 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 ..
- A safety study of oral valganciclovir maintenance treatment of cytomegalovirus retinitisJacob 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...
- Optimizing prostate cancer suicide gene therapy using herpes simplex virus thymidine kinase active site variantsAllan 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...
- Prodrugs: design and clinical applicationsJarkko Rautio
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI 70211 Kuopio, Finland
Nat Rev Drug Discov 7:255-70. 2008b>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...
- The role of hypoxia-activated prodrugs in cancer therapyW 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 ..
- Paclitaxel delivery systems: the use of amino acid linkers in the conjugation of paclitaxel with carboxymethyldextran to create prodrugsShu ichi Sugahara
The Second Research Department of Central Technology Laboratory, AsahiKasei Corporation, Fuji, Shizuoka, Japan
Biol Pharm Bull 25:632-41. 2002....
- The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3Christopher 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...
- A calorimetric evaluation of the interaction of amphiphilic prodrugs of idebenone with a biomembrane modelR 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...
- Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrugJinsong 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...
- Improving the efficacy of antibody-based cancer therapiesP 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...
- Cytochrome P450-activated prodrugs: targeted drug deliveryKristiina 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...
- Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugsMaria 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 ..
- The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer modelM K Nyati
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109 0010, USA
Gene Ther 9:844-9. 2002....
- Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virusJ Foloppe
Transgene SA, 11 rue de Molsheim, Strasbourg Cedex, France
Gene Ther 15:1361-71. 2008....
- Tumour tropism and anti-cancer efficacy of polymer-based doxorubicin prodrugs in the treatment of subcutaneous murine B16F10 melanomaL W Seymour
Institute for Cancer Studies, University of Birmingham School of Medicine, UK
Br J Cancer 70:636-41. 1994....
- Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodentsMar 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...
- Combination of cytosine deaminase with uracil phosphoribosyl transferase leads to local and distant bystander effects against RM1 prostate cancer in miceAparajita 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'...
- L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatmentAntonio 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 ..
- Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkersHong 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...
- Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxelJ 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...
- Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence mutagenesis improve prodrug-mediated tumor cell killingM E Black
Department of Pharmaceutical Sciences, Washington State University, Pullman 99164 6534, USA
Cancer Res 61:3022-6. 2001....
- Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinaseAndrew 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 ..
- Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killingRainer 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...
- Optimized clostridium-directed enzyme prodrug therapy improves the antitumor activity of the novel DNA cross-linking agent PR-104Shie 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...
- In vitro and in vivo evaluation of polyoxyethylene esters as dermal prodrugs of ketoprofen, naproxen and diclofenacF 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...
- Prodrugs forming high drug loading multifunctional nanocapsules for intracellular cancer drug deliveryYouqing 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...
- Synthesis and study of controlled release of ibuprofen from the new acrylic type polymersMirzaagha 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...
- Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluationsSoumyajit 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. 2005The 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.
- Lessons learned from marketed and investigational prodrugsPeter Ettmayer
Novartis Institute for Biomedical Research, Brunnerstrasse 59, A 1235 Vienna, Austria
J Med Chem 47:2393-404. 2004
- Acyloxyalkyl ester prodrugs of FR900098 with improved in vivo anti-malarial activityRegina 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 ..
- Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugsSwati 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.
- Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracilH 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...
- Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infectionD 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...
- Exploiting tumour hypoxia in cancer treatmentJ Martin Brown
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford, California 94305, USA
Nat Rev Cancer 4:437-47. 2004
- IMPROVING SUICIDE GENES FOR CANCER GENE THERAPYMargaret 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...
- Preclinical Development of JS-K, a Novel NO-Generating Prodrug for CancerPaul 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 ..
- Microsomal Cytochromes P450 and their Interactions with their Redox PartnersLucy 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...
- CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGSStephen J Lippard; Fiscal Year: 2013..Carbon nanotubes and biodegradable nanoparticles are devised to deliver platinum prodrugs selectively to cancer cells, targeting specific receptors...
- Novel Mitochondrial Targeted Neuroprotectants for GlaucomaLeonard 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...
- A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of NucleosideJohn 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 ..
- Transscleral Transport & Polymeric Delivery of Antibody & Steroids for Macular EdAshim 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...
- Tumor drug delivery systems based on polymalic acidJulia 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...
- Participation in Cytochrome b5 in Anesthetic MetabolismLucy 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...
- Rigid-rod Peptides as Nanocarriers for Delivery of Cancer DrugsKatarzyna Slowinska; Fiscal Year: 2013..Therefore several prodrugs, typically containing PTX conjugated with the hydrophilic and hydrolyzable groups such as polycarboxylic acids, ..
- CHEMOPREVENTION OF SKIN CANCER PROGRAM PROJECTGeorge 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 ..
- AID-mediated genetic instability in BCR-ABL1-transformed B cell lineage leukemiaMARKUS 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 ..
- Inhibition of Carboxylesterase Metabolism by EthanolRobert 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...
- 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.
- DNA Pro-Drug Technology in Localized Wound Healing and Tissue RegenerationArthur A Decarlo; Fiscal Year: 2011....
- SPORE IN PROSTATE CANCERWILLIAM 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). ..
- Transmucosal Intra-Oral Drug Delivery System for THCMahmoud 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 ..
- Development of Novel Inducers of Non-Apoptotic Cell Death to Target GlioblastomaWilliam 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...
- Using vitamin D glucuronide pro-drugs to prevent/treat colon cancerJESSE 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. ..
- Transdermal delivery of 2-Arachidonoyl glycerol (2-AG) for the treatment of arthrAudra L Stinchcomb; Fiscal Year: 2012..We aim to synthesize hydrophilic prodrugs of 2-AG to improve permeation across the skin into synovial fluid...
- Tailor-made variants of site-specific recombinases as tools for genome engineerinYuri 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...
- Development of Novel Class of Anti-Inflammatory DrugsKEN 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. ..
- Combination Therapy With 5-FU and PDT For The Treatment Of Post-Transplant PremalEdward 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 ..
- Use of Beta-Lapachone for Lung Cancer ChemotherapyDavid 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 ..
- Transdermal Cannabidiol Prodrug DeliveryAudra 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...
- New treatment for androgen sensitive and resistant prostate cancerAngela M Brodie; Fiscal Year: 2013....
- Estrogen-Derived Para-Quinol Intervention in Alzheimer's DiseaseMary 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...
- Imaging of Cardiac Transplant RejectionMatthias 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...
- Genetic Variants of Human Carboxylesterase 1 Influence the Activation and AntivirJohn 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, ..
- Therapeutics Targeting Macrophages/Microglia to Eradicate CNS HIV-1 ReservoirsWilliam 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 ..
- Optimization of pyrimidinyl prodrugs (PYPs) for malaria chemotherapyPRADIPSINH RATHOD; Fiscal Year: 2009yrimidinyl Prodrugs for Malaria Significance: Malaria parasites infect about a billion individuals and cause up to 2 million deaths per year...
- SYNTHESIS AND BIOTRANSFORMATION OF ANTI-HIV PRODRUGSChung K Chu; Fiscal Year: 2010..potency, bioavailability, and selective targeted delivery to the lymphatic system and brain, we propose several prodrugs of DAPD...
- Prodrugs of NAAG Peptidase Inhibitors for the Treatment of SchizophreniaJia 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 ..
- HER2-targeted exosomal delivery of therapeutic mRNA for enzyme pro-drug therapyAC 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 ..
- Hypoxia-Selective Kinase Inhibitors for Leukemia TherapyMarina 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...
- Nitogen reduction and xenobiotic responseLauren A Trepanier; Fiscal Year: 2010..The ultimate goal of these studies is to find better ways to prevent these adverse reactions. ..
- Boronated nucleosides for neutron capture therapy of brain tumorsWerner 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...
- Development of a Novel Semen-Activated Prodrug as an Anti-HIV MicrobicideROBERT 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...
- Transdermal Cannabinoid Prodrug Treatment for Cannabis Withdrawal and DependenceLynn 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...
- NALTREXONE PRODRUGS FOR TRANSDERMAL DELIVERYAudra 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 ..
- Broad Spectrum Antiviral Nucleoside Phosphonate AnalogsJohn 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 ..
- Using FAP to Selectively Target Epithelial CancersWilliam 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. ..
- Role and Relevance of Pept1 in Drug Absorption, Disposition, and DynamicsDavid 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...
- Glutathione S-Transferases in Drug and Stress ResponseKenneth 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-..
- Selection of the Optimal Nucleoside Triphosphate Mimic Prodrug Inhibitor of HCV RPHILLIP 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 ..
- Structure/function studies of nucleoside analog activating enzymesArnon Lavie; Fiscal Year: 2009Nucleoside analogs (NAs) - a mainstay of anticancer therapy - are prodrugs that upon conversion into their phosphorylated form mimic naturally occurring nucleotides...
- Riluzole Prodrugs for Melanoma and ALSALLEN 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 ..
- Development of JS-K as an anti-leukemic agentPaul 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...
- Inhibition of the Nonmevalonate pathway to Kill Mycobacterium tuberculosisCYNTHIA 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 ..
- Meropenem Prodrugs for XDR-TBRory P Remmel; Fiscal Year: 2013..The objectives of this application are to synthesize prodrugs of meropenem that are orally bioavailable...
- Targeting hypoxic microenvironment in Acute Lymphocytic LeukemiaMarina Y Konopleva; Fiscal Year: 2013....
- Harnessing ectonucleotidases to treat chronic painMark 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...
- UPLC with Tandem MS for Sensitive Quantitative Analysis of Small MoleculesMichelle A Rudek; Fiscal Year: 2010..g., preclinical development of thapsigargin prodrugs (R01), agents in Caseating Granulomas (R01), and agents in Buruli ulcers (R01))...
- Synthesis and discovery of biologically active cell-permeable cyclic peptidesR 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...
- 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...
- In vitro detection of anti-TB liver metabolites in early drug discoveryScott G Franzblau; Fiscal Year: 2013..Compounds that would only be active after metabolism in the liver (prodrugs) are not detected in high throughput screens...
- Role of a Novel Absorption Mechanism in Metformin Disposition and PharmacologyDhiren R Thakker; Fiscal Year: 2013..Metformin analogs or prodrugs with improved therapeutic profile can be conceived based on the findings of this research
- DNA Repair in Cancer Biology and TherapyPeter 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 ..
- Rational Design of NRTI for Drug Resistant HIV-1John 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...
- Transcleral Therapeutics in Diabetic RetinopathyUday 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...
- Nanoscale Metal-organic Frameworks for Imaging and Therapy of Pancreatic CancerJen 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...
- A Silicate Prodrug Strategy for Enhancing Nanoparticle Delivery of TaxanesCHRIS MACOSKO; Fiscal Year: 2011DESCRIPTION (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 ..
- Genetic and Chemically Programmed Nanoparticles for Prodrug TherapyM 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...
- Ocular Disposition of Antimicrobial AgentsAshim 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 ..
- ANTI-AIDS NUCLEOSIDE CONJUGATES OF ETHER PHOSPHOLIPIDSCHUNG HONG; Fiscal Year: 1992..Since the proposed prodrugs are conjugates of two biologically active moieties (nucleoside and ether lipid), the improved therapeutic effects ..
- AZIDE TECHNOLOGY FOR DRUG DEVELOPMENTKyoichi 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 ..
- Vidarabine Prodrugs as Anti-Pox Virus AgentsJohn 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...
- A Controlled Trial of NAC for Cocaine DependenceRobert Malcolm; Fiscal Year: 2009..placebo;and 3) to study cocaine craving/cue reactivity and withdrawal symptoms in subjects taking NAC or placebo. ..
- NAAG Peptidase Inhibitors for the Treatment of Traumatic Brain InjuryJia 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 ..
- Transgenic porphyric Leishmania as suicidal live vaccines against leishmaniasisKwang Poo Chang; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Improving Absorption and Targeting of Antiviral DrugsJohn 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 ..
- Type I Diabetes Model in ZebrafishMeera 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. ..
- CYCLIC PRODRUGS OF OPIOID PEPTIDESRONALD 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 ..
- MULTIFUNCTIONAL PHOSPHONOFORMATE PRODRUGS AGAINST HIV 1Andre 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...
- Development of Anticancer 1,2-Bis(sulfonyl)hydrazinesAlan 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-..