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  • novel prodrugs
  • A method is provided for converting therapeutic glycosidase inhibitors to novel prodrugs by phosphorylation of a free hydroxyl group on the molecule to substantially reduce the glycosidase inhibitory activity without thereby substantially reducing the therapeutic activity. (google.es)
  • derivatives
  • Prodrugs are inactive, bioreversible derivatives of active drug molecules that must undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then elicit its desired pharmacological effect in the body. (aspetjournals.org)
  • In most cases, prodrugs are simple chemical derivatives that are only one or two chemical or enzymatic steps away from the active parent drug. (aspetjournals.org)
  • Liposomal prodrugs including these specific derivatives of camptothecin restrained by a liposomal delivery system are also described. (google.com)
  • This article briefly describes bile acid transport proteins involved in enterohepatic circulation, summarizes the key factors affecting on the transport by these proteins, and reviews the use of bile acids and their derivatives in designing prodrugs capable of exploiting the bile acid transport system. (mdpi.com)
  • This review concentrates on bystander effects and drug development with regard to these enzyme prodrug combinations, namely herpes simplex virus thymidine kinase (HSV-TK) with ganciclovir (GCV), cytosine deaminase (CD) from bacteria or yeast with 5-fluorocytodine (5-FC), and bacterial nitroreductase (NfsB) with 5-(azaridin-1-yl)-2,4-dinitrobenzamide (CB1954), and their respective derivatives. (mdpi.com)
  • Type IIC
  • For Type II prodrugs, the conversion process could either take place extracellularly in the milieu of gastrointestinal fluids (Type IIA), in the systemic circulation and/or other systemic extracellular fluid compartments (Type IIB), or near therapeutical target cells (Type IIC). (mdpi.com)
  • anticancer
  • Tioguanine and tioguanine-generating prodrugs have been investigated as anticancer and immunosuppressive agents, including use in cancer immunotherapy. (epfl.ch)
  • The bacterial and yeast cytosine deaminases ( 9 , 10 ) convert the nontoxic prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), which is widely used in the treatment of a range of cancers, including colorectal and breast cancers ( 11 , 12 ). (aacrjournals.org)
  • Sulforaphane preconditioning sensitizes human colon cancer cells towards the bioreductive anticancer prodrug PR-104A. (oncologynurseadvisor.com)
  • antiviral nucleoside
  • For Type I prodrugs, conversion occurs intracellularly ( e.g. , antiviral nucleoside analogs, lipid-lowering statins), whereas conversion of Type II prodrugs occurs extracellularly, for examples in digestive fluids, systemic circulation or other extracellular body fluids ( e.g. , etoposide phosphate, valganciclovir, fosamprenavir). (mdpi.com)
  • Novel Hepatotrophic Prodrugs of the Antiviral Nucleoside 9-(2-Phosphonylmethoxyethyl)adenine with Improved Pharmacokinetics and Antiviral Activity. (springer.com)
  • enzyme
  • For example, antibody, or virus-directed enzyme are all types of Type II prodrug. (wikibooks.org)
  • The bioconversion of the prodrugs to their active parent drugs is by way of enzyme activity of hydrolases. (wikibooks.org)
  • The success of enzyme/prodrug cancer therapy is limited by the uncertainty in the delivery of the enzyme in vivo . (aacrjournals.org)
  • This study shows the use of noninvasive magnetic resonance (MR) and optical imaging to image the delivery of a prodrug enzyme. (aacrjournals.org)
  • The delivery of a multimodal imaging reporter functionalized prodrug enzyme, cytosine deaminase, was detected by MR and optical imaging in MDA-MB-231 breast cancer xenografts. (aacrjournals.org)
  • The optimal time window for prodrug administration was determined to be 24 h, at which time the enzyme continued to show high enzymatic stability in tumors but was biodegraded in the liver. (aacrjournals.org)
  • These preclinical studies show the feasibility of using a MR-detectable prodrug enzyme to time prodrug administration in enzyme/prodrug cancer therapy. (aacrjournals.org)
  • Imaging the tissue pharmacokinetics of a drug-activating enzyme would therefore be ideal to optimize the timing of prodrug delivery. (aacrjournals.org)
  • Here, for the first time, we report on the in vivo detection of a drug-activating enzyme functionalized with multimodal magnetic resonance (MR) and optical imaging reporters to provide image-guided delivery of prodrug. (aacrjournals.org)
  • As a prototype agent, we selected the nonmammalian enzyme cytosine deaminase as the prodrug enzyme. (aacrjournals.org)
  • Rautio
  • 6 Prodrugs Designed to Target Transporters for Oral Drug Delivery ( Mark S. Warren and Jarkko Rautio ). (wiley.com)
  • uptake
  • ACH-3422 appears to have high oral bioavailability, rapid uptake and conversion of the prodrug into the monophosphate within the liver, and a pharmacokinetic profile supportive of once-daily dosing. (cnbc.com)
  • Here, we attempted to enhance the brain uptake of cationic dopamine by utilizing the large amino acid transporter 1 (LAT1) at the BBB by prodrug approach. (springer.com)
  • The brain uptake after intravenous administration and the dopamine-releasing ability in the rat striatum after intraperitoneal administration were also determined for the most promising prodrug. (springer.com)
  • The prodrug with phenylalanine derivative as the promoiety had both higher affinity for LAT1 and better brain uptake properties than those with an alkyl amino acid -mimicking promoiety. (springer.com)
  • Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats. (springer.com)
  • Brain uptake of ketoprofen-lysine prodrug in rats. (springer.com)
  • inhibitor
  • ACH-3422 is a small-molecule, nucleotide prodrug inhibitor of HCV NS5B polymerase. (cnbc.com)
  • New arylsulfonyl proton pump inhibitor (PPI) prodrug forms were synthesized. (mdpi.com)
  • Garst, M. 1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs. (mdpi.com)
  • optimize
  • It is expected that continued studies to optimize the bystander effects and other properties of prodrugs and the activated species they generate will contribute to improvements in the effectiveness of suicide gene therapy. (hindawi.com)
  • preclinical
  • If anything, this alternative should be considered in the early stages of preclinical development, bearing in mind that prodrugs may alter the tissue distribution, efficacy, and even toxicity of the parent drug. (aspetjournals.org)
  • NEW HAVEN, Conn., Nov. 2, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced a poster presentation detailing the preclinical profile of ACH-3422, a uridine-analog nucleotide prodrug being advanced for the potential treatment of chronic hepatitis C viral infection (HCV). (cnbc.com)
  • overcome
  • Numerous prodrugs designed to overcome formulation, delivery, and toxicity barriers to drug utilization have reached the market. (aspetjournals.org)
  • Another fallacy is that prodrugs are simply of academic interest and do not have industrial applications in attempts to overcome bioavailability and toxicity problems. (aspetjournals.org)
  • Professor Rautio's research focuses on chemistry-based methods, especially prodrugs, to overcome the liabilities of drugs. (wiley.com)
  • tissue
  • This can not only improve the efficacy of the drug but also decrease systemic and/or unwanted tissue/organ-specific toxicity (T). Development of a prodrug with improved properties may also represent a life-cycle management opportunity. (aspetjournals.org)
  • drugs
  • Prodrugs are a new class of drugs that, upon administration, are inactive. (wikibooks.org)
  • Probably the most commonly used illicit prodrug is heroin, which is metabolised into morphine in the body, but both are Class A drugs in the UK so there's no legal benefit to having one rather than the other. (mindhacks.com)
  • The prodrug concept has been used to improve undesirable properties of drugs since the late 19th century, although it was only at the end of the 1950s that the actual term prodrug was introduced for the first time. (aspetjournals.org)
  • In fact, approximately 20% of all small molecular drugs approved during the period 2000 to 2008 were prodrugs. (aspetjournals.org)
  • In addition, the prodrug strategy has been used to increase the selectivity of drugs for their intended target. (aspetjournals.org)
  • These results indicate that attachment of phenylalanine to a cationic drug via an amide bond from the meta-position of its aromatic ring could be highly applicable in prodrug design for LAT1-mediated CNS-delivery of not only anionic but also cationic polar drugs. (springer.com)
  • Design
  • The design of an appropriate prodrug should never be viewed as a last resort. (aspetjournals.org)
  • Although prodrug design is very challenging, it can still be more feasible and faster than searching for an entirely new therapeutically active agent with suitable ADMET properties. (aspetjournals.org)
  • This review summarizes the current state of prodrugs, especially the polyprodrug platform, and focuses on the logical design for clinical use and proposes some practical prospects for the future development of the prodrug platform. (rsc.org)
  • By careful prodrug design, the active drug can be released in a particular location of the body or even over a desired timescale. (cystinosis.org.uk)
  • It summarizes current experiences and strategies for the rational design of prodrugs, beginning at the early stages of the development process, as well as discussing organ- and site-selective prodrugs. (wiley.com)
  • drug
  • Esters are found most commonly in commercial prodrugs, such as the drug oseltamivir. (wikibooks.org)
  • In this paper, a new classification system for prodrugs is proposed to provide useful information about where in the body a prodrug is converted to the active drug. (mdpi.com)
  • In this system, prodrugs are classified into Type I or Type II and the respective Subtypes IA, IB, IIA, IIB or IIC based on their sites of conversion into the final active drug form. (mdpi.com)
  • In conclusion, the new system of classification will add to existing knowledge of prodrug classifications, and will provide improved insight into the contributory roles of both prodrug and active drug in the product's efficacy and safety, and their risk-benefit assessment. (mdpi.com)
  • Compounds that are weak or inactive until the body transforms them into an active drug are called prodrugs , and this is the first situation that I can think of where a legal prodrug has been found for an illegal drug. (mindhacks.com)
  • Choose the menu Chemistry/Generate Drug from Prodrug and a dialog box will be displayed. (molsoft.com)
  • You can choose to output the results in the "in-addition" mode where the converted drug will be in the row below the prodrug or "replace original" whereby the prodrug will be replaced with the converted drug. (molsoft.com)
  • Pavan B, Dalpiaz A. Prodrugs and endogenous transporters: are they suitable tools for drug targeting into the central nervous system? (springer.com)
  • This chapter reviews the liver-targeting strategies explored to date and, more specifically, the strengths and weaknesses of various prodrug strategies used for liver-specific drug delivery. (springer.com)
  • A prodrug is a drug that is administered in an inactive - or significantly less active - form. (thefreedictionary.com)
  • TAF, an oral prodrug of tenofovir, delivers more tenofovir diphosphate (TFV-DP, the active form of the drug) to PBMCs than does TDF and has greater antiviral activity than TDF in clinical studies. (natap.org)
  • therapy
  • This review focuses on the prodrugs used in suicide gene therapy. (hindawi.com)
  • Both prodrugs and their activated species should have good distributive properties, so that the resulting bystander effects can maximize the effectiveness of the therapy, since gene transduction efficiencies are generally low. (hindawi.com)
  • A total of 42 prodrugs explored for use in suicide gene therapy with 12 different enzymes are discussed, particularly in terms of their physiocochemical properties. (hindawi.com)
  • The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC) platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity. (dovepress.com)
  • therapeutic
  • Many therapeutic agents are manufactured and administered in prodrug forms. (mdpi.com)
  • Type IA prodrugs refer to those that are converted at the cellular targets of therapeutic actions, whereas Type IB prodrugs' conversion occurs in the primary metabolic tissues such as liver, gut, or lung. (mdpi.com)
  • physicochemical properties
  • It develops new molecular entities (NMEs) using incremental innovation and prodrug technology targeted to provide better pharmacokinetic, pharmacodynamics, physicochemical properties, and to enable the development of known agents for both existing and new indications. (thefreedictionary.com)
  • bystander
  • Many of the early antimetabolite-based prodrugs provide very polar activated forms that have limited abilities to diffuse across cell membranes, and rely on gap junctions between cells for their bystander effects. (hindawi.com)
  • normal tissues
  • Sulforaphane, found in broccoli and other cruciferous vegetables such as cauliflower and kale, may increase the susceptibility of a subset of cancer to prodrug treatments while avoiding harm to normal tissues. (oncologynurseadvisor.com)
  • Pharmacokinetics
  • The gabapentin prodrug XP13512 has several potential advantages over standard gabapentin for treating RLS: The agent has linear pharmacokinetics, doesn't reach a saturation point, and is formulated for sustained release. (thefreedictionary.com)
  • patent
  • Biopharmaceutical company Biohaven Pharmaceutical Holding Company Ltd (NYSE:BHVN) reported on Wednesday the receipt of a Notice of Allowance from the US Patent and Trademark Office (USPTO) covering certain prodrugs of the glutamate modulating agent riluzole. (thefreedictionary.com)