• Fig. 4: PT-MN-mediated prodrug activation in vitro. (nature.com)
  • In this master's thesis the goal was to establish non-cell-based in vitro methods to study prodrug bioactivation. (helsinki.fi)
  • The prodrugs were incubated in liver and intestinal S9 fractions and blood plasma to study in vitro bioactivation of these prodrugs. (helsinki.fi)
  • The in vitro incubation used in this study can be used for screening prodrugs. (helsinki.fi)
  • However both low and high activation rates were observed thus the clinically relevant in vivo APC formation can be achieved with both high and low bioactivation in vitro. (helsinki.fi)
  • Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo , which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting. (hindawi.com)
  • We have designed and tested both in vitro and in vivo , a monoamine oxidase B (MAOB) specific prodrug, PAM-OBG, that is converted by glioma MAOB into the MGMT inhibitor O 6 -benzylguanine (O 6 BG) and the DNA crosslinking agent acrolein. (oncotarget.com)
  • A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on in vitro anti-leukaemic activity and calculated "drug-likeness" properties, in vitro and in vivo pharmacokinetics studies and hERG liability testing. (rsc.org)
  • Broad-Spectrum In Vitro Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524). (cdc.gov)
  • On the basis of pharmacokinetic results obtained in rats and mice exposed to chloroform by inhalation, and of enzymatic studies in human tissues in vitro , in vivo metabolic rate constants (VmaxC = 15.7 mg/hour/kg, Km = 0.448 mg/L) were defined for humans (Corley et al. (cdc.gov)
  • Basileas Onkologie-Medikamentenkandidat BAL101553 (Prodrug des Wirkstoffs BAL27862)2 wird für die potenzielle Behandlung verschiedener Krebserkrankungen entwickelt. (basilea.com)
  • Basileas niedermolekularer Medikamentenkandidat BAL101553 (Prodrug des Wirkstoffs BAL27862)4 wird für die potenzielle Behandlung verschiedener Krebserkrankungen entwickelt. (basilea.com)
  • Though several studies have been carried out on various prodrugs, surprisingly very few reviews on different carriers, which can be used for prodrug synthesis were published to date. (ijpsonline.com)
  • In this review different types of carriers, which can be used for prodrug synthesis are summarized. (ijpsonline.com)
  • The objective of this review is to provide the researchers with a compilation of which carriers would be suitable for prodrug synthesis and what would be their benefits. (ijpsonline.com)
  • An oral sphingosine 1-phosphate receptor 1 (S1P(1)) antagonist prodrug with efficacy in vivo: discovery, synthesis, and evaluation. (novartis.com)
  • Included is the design and attempted synthesis of a series of prodrugs, which based on the results of chapter 1, would be interesting candidates for an in-vivo PK study to determine their duration of action relative to the parent drug candidates, and thus feasibility as sustained release delivery agents. (nottingham.ac.uk)
  • Prodrugs are derivatives of drug molecules that are pharmacologically inactive but require either chemical or enzymatic transformation to release the active drug in vivo in order to exert a pharmacological effect. (ijpsonline.com)
  • Prodrugs are pharmacologically inactive molecules which undergo metabolic bioactivation in vivo to form pharmaceutically active agents. (helsinki.fi)
  • Restoring extracellular glutamate with systemic administration of cysteine prodrugs prevented the reinstatement of cocaine seeking. (jneurosci.org)
  • In vivo pharmacokinetics and metabolism of LOPOX and LOP were compared in the dog. (aspetjournals.org)
  • In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. (nature.com)
  • Fig. 5: PT-MN-mediated prodrug activation in vivo for anticancer studies. (nature.com)
  • 1. Kratz F, Muller IA, Ryppa C, Warnecke A. Prodrug strategies in anticancer chemotherapy. (jptcp.com)
  • These prodrugs subsequently undergo enzymatic or non-enzymatic cleavage to release the active drug moiety (figure 1) [ 12 , 13 ]. (ijpsonline.com)
  • It outlines the discovery of compound 24 as a novel, dibasic, pH-sensitive, self-cleaving, muscarinic prodrug capable of withstanding enzymatic cleavage in order to liberate an active muscarinic receptor antagonist at a sustained rate over 24 hours. (nottingham.ac.uk)
  • This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues. (nature.com)
  • Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. (hindawi.com)
  • Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. (hindawi.com)
  • In the present study, we used FDG microPET as an in vivo evaluation method to assess the early therapeutic efficacy of the suicide gene therapy. (hindawi.com)
  • However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. (nature.com)
  • Bioorthogonal chemistry for prodrug activation in vivo . (bvsalud.org)
  • Fig. 6: Drug and prodrug concentrations versus time and Pd content in tissues after different treatments. (nature.com)
  • Prodrug concentrations were quantified from the incubation samples using liquid chromatography- tandem mass spectrometry (LC-MSMS) methods developed for this study. (helsinki.fi)
  • All of the studied prodrugs produced at least low concentrations of APC in one or more incubations. (helsinki.fi)
  • Therefore, a mechanism that may account for the ameliorative effect of cysteine prodrugs on cocaine seeking is that the increase in extracellular glutamate produced by activating xc- restores tone on presynaptic mGluR2/3 and thereby reduces synaptic glutamate release. (jneurosci.org)
  • We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc(*-)) and H(2)O(2) in the extracellular space compared with blood. (nih.gov)
  • The prodrug strategy implementation in the last 20 y has led to a steady advancement in the biopharmaceutical, physicochemical and/or pharmacokinetic attributes of the pharmacologically active compounds. (ijpsonline.com)
  • Prodrugs have been designed to improve so called drug-like properties of active parent compounds (APC) i.e. to increase solubility or absorption and to reduce first-pass metabolism etc. (helsinki.fi)
  • Four commercially available prodrugs (bambuterol, olmesartan medoxomil (OM), candesartan cilexetil (CC) and famciclovir) were used as test compounds. (helsinki.fi)
  • However, in these studies, the therapeutic efficacies were mainly determined by using calipers to measure tumor sizes, while lacking in vivo evaluation on the early treatment responses of tumors to TK/GCV. (hindawi.com)
  • Chapter 4 presents the in vivo evaluation of poly(2-methacryloyloxyethyl phosphorylcholine)-doxorubicin (polyMPC-Dox) prodrugs for treating human ovarian tumors (SKOV-3). (umass.edu)
  • 2006). „Improved bioavailability of the mGlu2/3 receptor agonist LY354740 using a prodrug strategy: in vivo pharmacology of LY544344" . (wikipedia.org)
  • In addition, it follows the development and implementation of a novel cleavable prodrug system from initial design stages, through to final in-vivo PK studies, as a method of efficaciously delivering an active muscarinic agent over a sustained period in attempt to increase the duration of action of an existing muscarinic receptor drug. (nottingham.ac.uk)
  • In the second experiment, cocaine-primed reinstatement of drug seeking was used to determine whether blocking mGluR2/3 prevents the capacity of the cysteine prodrug N -acetylcysteine to inhibit drug seeking. (jneurosci.org)
  • Zanamivir and oseltamivir, which are prodrugs processed in vivo to their active form, can inhibit both IAV and IBV replication, reducing the duration time of virus release. (pharmacytimes.com)
  • Other metabolism of the prodrug and APC (nonproductive metabolism) was studied by comparing incubation with and without cofactors of metabolizing enzymes. (helsinki.fi)
  • Studying the rate of prodrug formation alone estimations about clinically relevant bioactivation rates cannot be concluded. (helsinki.fi)
  • The prodrug approach is rapidly becoming a crucial part in the stratagem of delivery of drugs. (ijpsonline.com)
  • and in vivo administration of mGluR2/3 agonists has potent behavioral effects ( Kenny and Markou, 2004 ). (jneurosci.org)
  • Several PET molecular imaging agents could be used for monitoring tumor responses to prodrug activation in gene therapy. (hindawi.com)
  • The subsequent in-vivo pharmacokinetic studies demonstrate that when inhaled independently, over 99% of the active drug was eliminated from the lung tissue within 3 hours, but when delivered as a prodrug, sustained prodrug activation meant that the drug was present in the lung at a pharmaceutically relevant concentration for over 24 hours, with no detected exposure of the drug to blood plasma. (nottingham.ac.uk)
  • Around 10 % of marketed medicines can be categorized as prodrugs currently, and also that during 2008, 33 % of approved small molecular weight drugs were prodrugs [ 5 - 7 ]. (ijpsonline.com)
  • The newly identified compound was shown to have pro-oxidant activity and in silico molecular docking studies indicate a prodrug mode of action. (rsc.org)
  • The prodrug approach using various carriers has evolved as a significant tool in surmounting different obstacles in relation to drug formulation and targeting. (ijpsonline.com)
  • Prodrugs have better delivery properties that surpass the parent drug molecule [ 1 ]. (ijpsonline.com)
  • Prodrug concept is justified because it enables the active drug to overcome the barrier that would impede it from reaching the site of action to exert the required pharmacological activity. (ijpsonline.com)
  • Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans. (aspetjournals.org)
  • Chapter 2: Describes the use of prodrug systems as mechanisms for improving drug delivery. (nottingham.ac.uk)
  • Conclusion: A dibasic, self-activating prodrug (Compound 24) has been created which displays a much-increased lung tissue retention relative to the parent drug (Compound 1). (nottingham.ac.uk)
  • Finally, Chapter 5 augments the polyMPC prodrug concept with the development of polymer-temozolomide (TMZ) conjugates intended for glioblastoma treatment. (umass.edu)
  • This system, if successful would represent a remarkable achievement in that the prodrug design could be developed to suit a wide range of chemical structures, and thus has the potential improve the inhaled PK profile of a wide variety of inhaled pharmaceuticals and thus massively expedite the development of novel-long acting treatments. (nottingham.ac.uk)
  • Our objective was to use existing in vivo mouse PK data for remdesivir and its metabolites to develop a mechanism-based model to allometrically scale and simulate the human PK of remdesivir in plasma and NTP in lung homogenate. (nih.gov)
  • Chapter 3: Develops further the prodrug system introduced in chapter 1, this time focusing on an intracellular PI3K δ target. (nottingham.ac.uk)
  • Chapter 4: Investigates how the dibasic moiety of the prodrug design affects the distribution of the prodrug in lung tissue. (nottingham.ac.uk)
  • This chapter attempted to visualise the effect of incorporating a dibasic moiety into the prodrug design on the distribution and organelle sequestration. (nottingham.ac.uk)
  • Directed evolution of artificial metalloenzymes for in vivo metathesis. (nature.com)
  • Polymer conjugation significantly improved the solution stability of TMZ, and the antitumor activity of polyMPC-TMZ prodrugs was demonstrated in TMZ-sensitive (U87MG) and TMZ-resistant (T98G) glioblastoma cell lines. (umass.edu)
  • The reduction of LOPOX to LOP was investigated to provide a pharmacokinetic basis for the pharmacodynamics and improved side effect profile of the prodrug. (aspetjournals.org)
  • Properties and selection of carriers or promoeities is a very important parameter in successful prodrug design. (ijpsonline.com)
  • Aims: The aim of this thesis was to design and evaluate a novel, self-activating, dibasic prodrug system as a possible method of achieving sustained delivery post inhalation. (nottingham.ac.uk)
  • In human ovarian tumor-bearing mice, polyMPC-Dox prodrugs with an approximate Dox loading of 19 weight percent accumulated in tumor tissue at twice the level of free Dox, and animals treated with polyMPC-Dox exhibited enhanced survival and retarded tumor growth compared to conventional Dox treatment. (umass.edu)
  • Mitochondrial Induced and Self-Monitored Intrinsic Apoptosis by Antitumor Theranostic Prodrug: In Vivo Imaging and Precise Cancer Treatment. (bioscience.co.uk)
  • No clear signs of nonproductive could be seen with the prodrugs studied with current method. (helsinki.fi)
  • Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. (hindawi.com)
  • NfsB is a dimeric flavoprotein enzyme that has broad electron acceptor specificity 15 and has been used in conjunction with prodrugs to selectively ablate cells in vertebrates. (cdc.gov)
  • By taking a lysosome-targeting fluorescent probe, replacing the functionality responsible for its lysosome targeting nature with the dibasic prodrug moiety, a distribution comparison can be created. (nottingham.ac.uk)
  • Carrier-linked prodrugs are for drugs with major drawbacks, which are linked to a nontoxic carrier or promoiety through covalent linkage to change or get rid of their undesirable physicochemical properties. (ijpsonline.com)
  • Remdesivir is a broad-spectrum nucleotide prodrug shown to be effective against enzootic coronaviruses. (nih.gov)