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. 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. In most cases, prodrugs are simple chemical derivatives that are only one or two chemical or enzymatic steps away from the active parent drug. However, some prodrugs lack an obvious carrier or promoiety but instead result from a molecular modification of the prodrug itself, which generates a new active compound. Numerous prodrugs designed to overcome formulation, delivery, and toxicity barriers to drug utilization have reached the market. In fact, approximately 20% of all small molecular drugs approved during the period 2000 to 2008 were prodrugs. Although the development of a prodrug can be very challenging, the prodrug approach represents a feasible way to improve the erratic properties of investigational drugs or drugs already on the market. This review introduces in de...Continue Reading
Prodrug approaches to enhancement of physicochemical properties of drugs IV: novel epinephrine prodrug
Steady-state kinetics of the overall oxidative phosphorylation reaction in heart mitochondria. Evidence for linkage of the energy-yielding and energy-consuming steps by freely diffusible intermediates and for an allosteric mechanism of respiratory control at coupling site 2
Hydrolysis of 3H-bambuterol, a carbamate prodrug of terbutaline, in blood from humans and laboratory animals in vitro
Importance of P450 reductase activity in determining sensitivity of breast tumour cells to the bioreductive drug, tirapazamine (SR 4233)
Purification and characterization of a rat liver enzyme that hydrolyzes valaciclovir, the L-valyl ester prodrug of acyclovir.
Reduction of 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide (tirapazamine, WIN 59075, SR 4233) to a DNA-damaging species: a direct role for NADPH:cytochrome P450 oxidoreductase
Synthesis, in vitro antiviral evaluation, and stability studies of bis(S-acyl-2-thioethyl) ester derivatives of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as potential PMEA prodrugs with improved oral bioavailability
Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats
Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir
Novel anthracycline-spacer-beta-glucuronide,-beta-glucoside, and -beta-galactoside prodrugs for application in selective chemotherapy
Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension
Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension
Activation of 3-amino-1,2,4-benzotriazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction
The hydrolysis of the prostaglandin analog prodrug bimatoprost to 17-phenyl-trinor PGF2alpha by human and rabbit ocular tissue
Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects
Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist
Hypoxia targeted gene therapy to increase the efficacy of tirapazamine as an adjuvant to radiotherapy: reversing tumor radioresistance and effecting cure
Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir.
Design, synthesis, and characterization of a series of cytochrome P(450) 3A-activated prodrugs (HepDirect prodrugs) useful for targeting phosph(on)ate-based drugs to the liver
Membrane transporter/receptor-targeted prodrug design: strategies for human and veterinary drug development
Fosamprenavir: a review of its use in the management of antiretroviral therapy-naive patients with HIV infection
Drug interactions with the potential to prevent prodrug activation as a common source of irrational prescribing in hospital inpatients
Identification of esterases expressed in Caco-2 cells and effects of their hydrolyzing activity in predicting human intestinal absorption
Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives
Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel
Brief report on the United States Food and Drug Administration Blood Products Advisory Committee recommendations for management of donors and units testing positive for hepatitis B virus DNA
Synthesis and characterization of a novel liver-targeted prodrug of cytosine-1-beta-D-arabinofuranoside monophosphate for the treatment of hepatocellular carcinoma
The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects
Identification of human reductases that activate the dinitrobenzamide mustard prodrug PR-104A: a role for NADPH:cytochrome P450 oxidoreductase under hypoxia
New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer
Oxygen dependence and extravascular transport of hypoxia-activated prodrugs: comparison of the dinitrobenzamide mustard PR-104A and tirapazamine
Frequency and clinical relevance of drug interactions with lovastatin and simvastatin: an observational database study
Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin
The biochemistry of drug metabolism--an introduction: part 6. Inter-individual factors affecting drug metabolism
Delivery of high levels of anti-proliferative nucleoside triphosphates to CYP3A-expressing cells as a potential treatment for hepatocellular carcinoma
The relationship between reduction in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated meta-analysis
Targeting of tamoxifen to enhance antitumour action for the treatment and prevention of breast cancer: the 'personalised' approach?
P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use
Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans
Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies
The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3
ACCF/AHA Clopidogrel clinical alert: approaches to the FDA "boxed warning": a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association
The physicochemical properties, in vitro metabolism and pharmacokinetics of a novel ester prodrug of EXP3174
Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis
Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys
Radiofluorination and biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB2 receptors
Prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs), more than meets the eye: a critical review
Design of prodrugs to enhance colonic absorption by increasing lipophilicity and blocking ionization
Highlights of recent developments and trends in cancer nanotechnology research--view from NCI Alliance for Nanotechnology in Cancer
Design, synthesis, and in vitro kinetics study of atenolol prodrugs for the use in aqueous formulations
Inhibition of phosphotidylinositol-3 kinase pathway by a novel naphthol derivative of betulinic acid induces cell cycle arrest and apoptosis in cancer cells of different origin
Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation
Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models
Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS)
Perspectives in Drug Development and Clinical Pharmacology: The Discovery of Histamine H1 and H2 Antagonists
Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges
Nanowired drug delivery for neuroprotection in central nervous system injuries: modulation by environmental temperature, intoxication of nanoparticles, and comorbidity factors
Enhanced Antitumor Activity of Monophosphate Ester Prodrugs of Gemcitabine: In Vitro and In Vivo Evaluation
Absorption and cleavage of enalapril, a carboxyl ester prodrug, in the rat intestine: in vitro, in situ intestinal perfusion and portal vein cannulation models
Relative bioavailability of orally administered fosphenytoin sodium injection compared with phenytoin sodium injection in healthy volunteers
Avasimibe encapsulated in human serum albumin blocks cholesterol esterification for selective cancer treatment
Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats
Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure
Component mobility by a minute quantity of the appropriate solvent as a principal motif in the acceleration of solid-supported reactions
The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study
Role of phenmetrazine as an active metabolite of phendimetrazine: evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys
A new prodrug form of Affibody molecules (pro-Affibody) is selectively activated by cancer-associated proteases
Methanolic Extract of Curcuma caesia Roxb. Prevents the Toxicity Caused by Cyclophosphamide to Bone Marrow Cells, Liver and Kidney of Mice
Synthesis, characterization and in vitro evaluation of amphiphilic ion pairs of erythromycin and kanamycin antibiotics with liposaccharides
Synthesis of a highly water-soluble acacetin prodrug for treating experimental atrial fibrillation in beagle dogs
Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies
Prodrug AST-003 Improves the Therapeutic Index of the Multi-Targeted Tyrosine Kinase Inhibitor Sunitinib
Analogs of the ATP-Sensitive Potassium (KATP) Channel Opener Cromakalim with in Vivo Ocular Hypotensive Activity
Modulating lipophilicity of rohitukine via prodrug approach: Preparation, characterization, and in vitro enzymatic hydrolysis in biorelevant media
Novel Synthetic PEGylated Conjugate of α-Lipoic Acid and Tempol Reduces Cell Death in a Neuronal PC12 Clonal Line Subjected to Ischemia
Dissociable effects of the prodrug phendimetrazine and its metabolite phenmetrazine at dopamine transporters
Prodrugs of a CXC Chemokine-12 (CXCL12) Neutraligand Prevent Inflammatory Reactions in an Asthma Model in Vivo
Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility
Pyrazolo[3,4-d]pyrimidine Prodrugs: Strategic Optimization of the Aqueous Solubility of Dual Src/Abl Inhibitors
Electrospun poly-l-lactide scaffold for the controlled and targeted delivery of a synthetically obtained Diclofenac prodrug to treat actinic keratosis
Development of a cancer-marker activated enzymatic switch from the herpes simplex virus thymidine kinase
12,13-Aziridinyl Epothilones. Stereoselective Synthesis of Trisubstituted Olefinic Bonds from Methyl Ketones and Heteroaromatic Phosphonates and Design, Synthesis, and Biological Evaluation of Potent Antitumor Agents
Activation of Phenyl 4-(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonates Prodrugs by CYP1A1 as New Antimitotics Targeting Breast Cancer Cells
Prodrugs of Pyrazolo[3,4-d]pyrimidines: From Library Synthesis to Evaluation as Potential Anticancer Agents in an Orthotopic Glioblastoma Model
Antiviral and Cytostatic Evaluation of 5-(1-Halo-2-sulfonylvinyl)- and 5-(2-Furyl)uracil Nucleosides
From solution to in-cell study of the chemical reactivity of acid sensitive functional groups: a rational approach towards improved cleavable linkers for biospecific endosomal release
Hormonal Contraceptives Differentially Suppress TFV and TAF Inhibition of HIV Infection and TFV-DP in Blood and Genital Tract CD4+ T cells
Redesigning the DNA-targeted chromophore in platinum-acridine anticancer agents: a structure-activity relationship study
Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure Prophylaxis
The importance of evaluating the chemical structures and strategies to avoid pitfalls in quantitative bioanalysis
A Single Site Population Study to Investigate CYP2D6 Phenotype of Patients with Persistent Non-Malignant Pain
Catechin prodrugs and analogs: a new array of chemical entities with improved pharmacological and pharmacokinetic properties
Hepatic, intestinal, renal, and plasma hydrolysis of prodrugs in human, cynomolgus monkey, dog, and rat: implications for in vitro-in vivo extrapolation of clearance of prodrugs
Characterization of recombinantly expressed rat and monkey intestinal alkaline phosphatases: in vitro studies and in vivo correlations
Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1
Overcoming challenges associated with the bioanalysis of an ester prodrug and its active acid metabolite
Enhanced in vitro antitumor efficacy of a polyunsaturated fatty acid-conjugated pH-responsive self-assembled ion-pairing liposome-encapsulated prodrug
Utility of a column-switching LC/MS/MS method in cytochrome P450 inhibition assays using human liver microsomes
PD806: a novel oral vascular disrupting agent shows antitumor and antivascular effects in vitro and in vivo
Feasibility and Utility of the Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing
Long-acting approaches for delivery of antiretroviral drugs for prevention and treatment of HIV: a review of recent research.
Lup-20(29)-en-3β,28-di-yl-nitrooxy acetate affects MCF-7 proliferation through the crosstalk between apoptosis and autophagy in mitochondria
Design, Synthesis, and Characterization of Schiff Base Bond-Linked pH-Responsive Doxorubicin Prodrug Based on Functionalized mPEG-PCL for Targeted Cancer Therapy
N-acetylcysteine modulates cyclophosphamide-induced immunosuppression, liver injury, and oxidative stress in miniature pigs
Synthesis and evaluation of water-soluble prodrugs of ursodeoxycholic acid (UDCA), an anti-apoptotic bile acid
Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals: Implications for Agonist-like Replacement Therapy
An Enzyme-Responsive "Turn-on" Fluorescence Polymeric Superamphiphile as a Potential Visualizable Phosphate Prodrug Delivery Vehicle
Orostachys japonicus A. Berger Extracts Induce Immunity-Enhancing Effects on Cyclophosphamide-Treated Immunosuppressed Rats
Catalytic asymmetric acetalization of carboxylic acids for access to chiral phthalidyl ester prodrugs
Omega-3 fatty acids modulate cyclophosphamide induced markers of immunosuppression and oxidative stress in pigs
Synergistic enzymatic and bioorthogonal reactions for selective prodrug activation in living systems
Self-delivery nanoparticles of an amphiphilic irinotecan-enediyne conjugate for cancer combination chemotherapy
How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?
Mitochondria-targeted aggregation induced emission theranostics: crucial importance of in situ activation
Toxicity mechanism-based prodrugs: glutathione-dependent bioactivation as a strategy for anticancer prodrug design
Epithelial Cells and Fibroblasts from the Human Female Reproductive Tract Accumulate and Release TFV and TAF to Sustain Inhibition of HIV Infection of CD4+ T cells
Pharmacokinetics and Clinical Pharmacology Considerations of GalNAc3 -Conjugated Antisense Oligonucleotides
Tricyclic Derivative of Acyclovir and Its Esters in Relation to the Esters of Acyclovir Enzymatic Stability: Enzymatic Stability Study
Synergistic study of a Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) combination on cell survival in EA.hy926 cells
Cyclic Peptides as Drugs for Intracellular Targets: The Next Frontier in Peptide Therapeutic Development.
The Small Molecule IMR-1 Inhibits the Notch Transcriptional Activation Complex to Suppress Tumorigenesis
Investigating the Role of Missense SNPs on ALDH 1A1 mediated pharmacokinetic resistance to cyclophosphamide
Esterase-Activatable Synthetic M+ /Cl- Channel Induces Apoptosis and Disrupts Autophagy in Cancer Cells
Spectroscopic studies of simultaneous binding of cyclophosphamide and imatinib mesylate to human holo-transferrin.
Discovery of Bivalent GalNAc-Conjugated Betulin as a Potent ASGPR-Directed Agent against Hepatocellular Carcinoma.
Emerging insights on drug delivery by fatty acid mediated synthesis of lipophilic prodrugs as novel nanomedicines.
Gemcitabine Lipid Prodrugs: The Key Role of the Lipid Moiety on the Self-Assembly into Nanoparticles.
Prodrug activation by gold artificial metalloenzyme-catalyzed synthesis of phenanthridinium derivatives via hydroamination.
Design of cellulose ether-based macromolecular prodrugs of ciprofloxacin for extended release and enhanced bioavailability
Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1H)-Quinolones with Single Dose Cures.
Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials.
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