Nucleoside transport inhibitor. Medical search. Frequent questions

Antiretroviral drugs for the treatment of HIV infections belong to six categories: Nucleoside and nucleotide reverse-transcriptase inhibitors, Non-nucleoside reverse-transcriptase inhibitors, protease inhibitors, entry inhibitors, co-receptor inhibitors and integrase inhibitors. (wikipedia.org)
Protease inhibitors such as lopinavir/ritonavir are thought to prevent polyprotein proteolysis. (woofahs.com)
Most experts currently believe that HIV type 1 (HIV-1) protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), especially stavudine and zidovudine, are implicated. (medscape.com)
FDA-approved ARVs are categorized into eight pharmacologic classes, including the nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 antagonists, postattachment inhibitors, integrase strand transfer inhibitors (INSTIs), and now the novel class of capsid inhibitors. (uspharmacist.com)

Both cidofovir and adefovir are nucleoside phosphonate analogs, a class of novel antivirals structurally related to natural nucleotides (Fig. 1 ). (aspetjournals.org)
Structure of acyclic nucleoside phosphonate analogs. (aspetjournals.org)
The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. (hal.science)
Consequently, our study has identified ABMA as an effective inhibitor of HSV-2, both in vitro and in vivo, for the first time and presents an alternative to nucleoside analogs for HSV-2 infection treatment. (hal.science)
Electrophysiological, fluorescence optical, and volume measurements were made to determine the effect of nucleoside analogs on the swelling-dependent chloride current (I Cl ) in NIH 3T3 fibroblasts and in human T cell lymphoma (H9) cells and the cAMP-dependent chloride current in CaCo cells. (biomedcentral.com)
The use of nucleoside analogs is a major strategy in the treatment of viral infections. (biomedcentral.com)
We show here that nucleoside analogs selectively block I Cl and the regulatory volume decrease (RVD) at concentrations one to two orders of magnitude lower than nucleotides, thus interfering with a vital cell regulatory mechanism at concentrations present in the plasma of patients treated with these drugs. (biomedcentral.com)

The interactions of two antiviral, acyclic nucleoside phosphonates, adefovir and cidofovir, with xenobiotic transporters was studied in intact killifish ( Fundulus heteroclitus ) renal proximal tubules by using fluorescent substrates, confocal microscopy, and quantitative image analysis. (aspetjournals.org)
Comparison of the inhibitory potencies of the nucleoside phosphonates with other substrates and inhibitors showed them to be moderate inhibitors of OAT1- and Mrp2-mediated transport. (aspetjournals.org)
1 Current assays used for screening of potential inhibitors of these enzyme classes rely on unstable antibodies or chemically labelled substrates, which prevents real-time analysis and makes the accurate determination of enzyme kinetics more difficult. (edu.au)
3 This offers a potentially powerful tool for high-throughput screening of kinase inhibitors, obviating the need for expensive antibodies or labelled substrates. (edu.au)
Fig. 1: Selected substrates transported by ABCB1, ABCG2 and ABCC1. (nature.com)
MRP4 has long been known to require reduced glutathione for the transport of bile acids [20], but the MRP4-mediated extrusion of other substrates such as halobenzoquinones may also depend on GSH, possibly via conjugate formation [21]. (solvobiotech.com)

The cardiovascular drug dipyridamole inhibits nucleoside transport and enhances antifolate cytotoxicity in vitro, but its clinical activity is compromised by binding to the plasma protein α1-acid glycoprotein (AGP). (figshare.com)
The effect of cAMP was reproduced by ATP, AMP, and adenosine, and was blunted by phosphodiesterase inhibitors or by dipyridamole which inhibits adenosine uptake. (jci.org)
Radioactivity accumulation was decreased by dipyridamole and by inhibitors of phosphodiesterases and ecto-5'-nucleotidase, assessing the existence of stepwise hydrolysis of extracellular cAMP and intracellular processing of taken up adenosine. (jci.org)

A subtype of equilibrative nucleoside transporter proteins that is insensitive to inhibition by 4-nitrobenzylthioinosine. (lookformedical.com)
A subtype of equilibrative nucleoside transporter proteins that is sensitive to inhibition by 4-nitrobenzylthioinosine. (lookformedical.com)
Inclusion criteria included elevated eIF4E levels compared to healthy volunteers and functional equilibrative nucleoside transporter 1 (ENT1). (haematologica.org)

A variety of enzymes are able to catalyze the final phosphorylation step for NRTIs, including nucleoside diphosphate kinase (NDP kinase), phosphoglycerate kinase, pyruvate kinase and creatine kinase, resulting in formation of respective antivirally active triphosphate analogues. (wikipedia.org)
Many studies have proposed multi-objective molecular generation methods and demonstrated their superiority using the public benchmark dataset for kinase inhibitor generation tasks. (bvsalud.org)
ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl)pyrido[2, 3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory. (axonmedchem.com)
Discovery of 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine, an orally active, non-nucleoside adenosine kinase inhibitor. (axonmedchem.com)
They are capable of transporting many of the common chemotherapeutics, including small-molecule tyrosine kinase inhibitors, taxanes, and anthracyclines (5). (whatisepigenetics.com)

Raltegravir is a human immunodeficiency virus (HIV)-integrase inhibitor that has been shown to alter the host immune response to HIV in addition to its direct antiviral effect. (microbiologyresearch.org)

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs and NtRTIs) began in the 1980s when the AIDS epidemic hit Western societies. (wikipedia.org)
The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. (wikipedia.org)
NRTIs approved by the FDA are zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine and the only nucleotide reverse-transcriptase inhibitor (NtRTI) approved is tenofovir (see table 4). (wikipedia.org)
NRTIs are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. (wikipedia.org)

Mechanisms whereby extracellular adenosine 3',5'-monophosphate inhibits phosphate transport in cultured opossum kidney cells and in rat kidney. (jci.org)
These results indicate that luminal degradation of cAMP into adenosine, followed by cellular uptake of the nucleoside by tubular cells, is a key event which accounts for the phosphaturic effect of exogenous cAMP and for the part of the phosphaturic effect of PTH which is mediated by cAMP added to the tubular lumen under the influence of the hormone. (jci.org)
A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. (lookformedical.com)

The first, and often rate limiting, phosphorylation step (for nucleoside analogues) are most commonly catalyzed by deoxynucleoside kinases. (wikipedia.org)
Addition of the second phosphate group to nucleoside monophosphate analogues is completed by the nucleoside monophosphate kinases (NMP kinases). (wikipedia.org)
Nucleoside analogues such as remdesivir and ribavirin are thought to prevent viral RNA synthesis. (woofahs.com)
Aim To review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues. (medscape.com)
Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. (medscape.com)
Long-term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. (medscape.com)
Conclusions Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. (medscape.com)
These agents are classified according to their chemical structures: the three nucleoside analogues include lamivudine, telbivudine and entecavir, whereas the two nucleotide analogues include adefovir dipivoxil, tenofovir disoproxil fumarate (TDF), [ 2 ] and the newly approved tenofovir alafenamide (TAF). (medscape.com)

Inhibition of Mrp2-mediated transport was abolished by 50 μM p -aminohippurate, indicating that adefovir and cidofovir entered the cells at the basolateral membrane on the classical organic anion transport system (OAT1). (aspetjournals.org)
Comparison with the cell-based studies revealed that pemetrexed enhancement requires substantial (≥90%) and durable inhibition of nucleoside transport. (figshare.com)
Pharmacologically active concentrations of the inhibitors can be achieved in vivo using prodrug approaches, but greater potency is required to evaluate inhibition of nucleoside rescue as a therapeutic maneuver. (figshare.com)
By preventing ADO phosphorylation, ADK inhibition increases intracellular ADO concentrations, altering the equilibrium of the bidirectional transport systems responsible for ADO reuptake with the net effect of increasing the local concentration of ADO in the extracellular compartment. (axonmedchem.com)
It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. (lookformedical.com)
In addition, they create a large production of reactive oxygen species, which leads to the production of cytokines, macrophage recruitment, and inhibition of glucose transport 4 (GLUT-4), along with a deficiency in insulin signaling and the hormones leptin and adiponectin. (medscape.com)

Importantly, both hOAT1 and rat renal organic anion transporter 1 (rROAT1) mediated saturable, probenecid-sensitive uptake of cidofovir, adefovir, and other nucleoside phosphonate antivirals. (aspetjournals.org)
Sever and Merzel 2023 determined the influence of the energetic and dynamic properties of SGLT1 as they are influenced by selected sugar uptake inhibitors on water permeation. (tcdb.org)

Since zidovudine was approved in 1987, six nucleosides and one nucleotide reverse-transcriptase inhibitor (NRTI) have been approved by FDA. (wikipedia.org)
Activation of nucleoside and nucleotide reverse-transcriptase inhibitors is primarily dependent on cellular entry by passive diffusion or carrier-mediated transport. (wikipedia.org)

The active ingredient is a strong antiviral plant extract called podophyllotoxin, which is a dividing cell metaphase inhibitor that binds to at least one of the tubulin-binding sites. (pharmacyplanet.com)
Importantly, we were able to demonstrate that these effects were specific to raltegravir and independent of the direct-acting antiviral effect of the drug, since treatment with the DNA polymerase inhibitor phosphonoacetic acid did not induce these host-targeted effects. (microbiologyresearch.org)
We show here a novel molecular mechanism by which antiviral drugs of the nucleoside analog family could lead to impairments of the kidney, bone marrow, gastrointestinal, and neuronal functions, and how these side effects could possibly be restricted by the presence of TDP or uridine. (biomedcentral.com)
The aim of the present study was to investigate the effect of antiviral drugs from the nucleoside analog family on I Cl . (biomedcentral.com)
Nucleosides have provided a plentiful source in structural leads in antiviral drug discovery. (auburn.edu)

Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. (lookformedical.com)

Proteins involved in the transport of NUCLEOSIDES across cellular membranes. (lookformedical.com)
In moths, pheromone binding proteins (PBPs) transport the hydrophobic pheromone molecules to the membrane-bound receptors across the aqueous sensillar lymph to trigger the neuronal response. (auburn.edu)
Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle. (wikipedia.org)

All non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized in the liver by CYP3A isoenzymes. (medscape.com)

Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. (elsevierpure.com)
High-resolution structures, biophysical and in silico studies have led to tremendous progress in understanding the mechanism of drug transport by these ABC transporters, and several promising therapies, including irradiation-based immune and thermal therapies, and nanomedicine have been used to overcome ABC transporter-mediated cancer chemoresistance. (nature.com)
Furthermore, genetic modification of ABC transporters by CRISPR-Cas9 and approaches to re-engineer amino acid sequences to change the direction of transport from efflux to import are briefly discussed. (nature.com)
Fig. 3: Substrate-binding pockets of ATP-binding cassette transporters and the drug transport cycle. (nature.com)

We are developing luminescent europium(III) complexes 2-6 capable of reversibly binding and discriminating between nucleoside tri-, di- and monophosphate anions in aqueous biological media (Figure 1). (edu.au)

The mechanism of phosphaturia induced by cAMP infusion and the physiological role of extracellular cAMP in modulation of renal phosphate transport were examined. (jci.org)
Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. (medscape.com)

5 This group also demonstrated that GLI1-inducible glucuronidation by UGT1A was not limited to these two drugs but included approximately forty other drugs from a variety of families, including nucleosides, antifolates, and anthracyclines. (haematologica.org)

Srikant, S. & Gaudet, R. Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters. (nature.com)
Glutathione as a conjugation partner or co-transported substrate plays multiple and partially undefined roles in the transport mechanism of MRPs, especially of MRP2. (solvobiotech.com)

The first nucleoside reverse-transcriptase inhibitor with in vitro anti-HIV activity was zidovudine. (wikipedia.org)

Sci Rep. 2018) and nucleoside analogue, RNA synthesis inhibitors (Kouba et al . (embl.org)
Methods Relevant articles related to nucleoside analogue safety were selected for review following extensive language- and date-unrestricted, electronic searches of the literature. (medscape.com)

Nucleoside salvage, which depends on plasma membrane transport, can compromise the activity of antifolates. (figshare.com)

New virus particles are assembled on membranes derived from the ERCGolgi complex and then transported out of the cell via the secretory pathway. (woofahs.com)

Purine transport in polymorphonuclear leukocytes. (uconn.edu)
AICA-Riboside, CAS 2627-69-2, is a cell-permeable nucleoside compound whose phosphorylated metabolite activates AMPK and acts as a regulator of de novo purine synthesis. (emdmillipore.com)

Collective domain motion facilitates water transport in SGLT1 ( Sever and Merzel 2023 ). (tcdb.org)

SGLT1 mediates the absorption of water, yet the mechanism and the effect of inhibitors is not well defined. (tcdb.org)

ATP, ADP, AMP) play crucial roles in a range of biological processes including energy transduction, cellular signalling and membrane transport. (edu.au)
Effect of phagocytosis on membrane transport of non-electrolytes. (uconn.edu)
Membrane transport in rabbit alveolar macrophage. (uconn.edu)
Membrane transport of nucleosides in rabbit polymorphonuclear leukocytes. (uconn.edu)
Temperature dependence of nucleoside membrane transport in rabbit alveolar macrophages and polymorphonuclear leukocytes. (uconn.edu)
The fusion inhibitor prevents the membrane of the host CD4 cell from fusing with the HIV envelope. (uspharmacist.com)

In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. (elsevierpure.com)

Both drugs reduced in a concentration-dependent manner the transport of fluorescein on the classical organic anion system and transport of fluorescein-methotrexate on multidrug resistance-associated protein 2 (Mrp2). (aspetjournals.org)

Specificities of transport systems and enzymes. (uconn.edu)
EFV acts as a mixed inducer and inhibitor, but, similarly to NVP, it primarily induces CYP3A and 2B6 enzymes. (medscape.com)

Nucleosides must be triphosphorylated, while nucleotides, which possess one phosphonated group, must be diphosphorylated. (wikipedia.org)
Given its ability to transport important intra- and intercellular mediators such as cyclic nucleotides and eicosanoids, the physiological repertoire of MRP4 is thought to cover platelet aggregation, cell migration and proliferation, angiogenesis, and cardiomyocyte contraction. (solvobiotech.com)

Postattachment inhibitors bind to the host CD4 receptor and block HIV from binding to the CCR5 and CXCR4 coreceptors. (uspharmacist.com)

Carbohydrates so far synthesized are sugers (L-nucleosides, etc.), deoxyamino sugars and their derivatives (D-ManNAc, zanamivir-related sialic acids), and oligosaccharides, such as LeX. (keio.ac.jp)

As the name suggests, efflux pumps transport foreign substances out of cells to prevent toxicities. (whatisepigenetics.com)

The specificity and characteristics of amino acid transport systems. (uconn.edu)

Neither drug inhibited transport of a fluorescent cyclosporin A derivative on P-glycoprotein. (aspetjournals.org)
The authors delve into two aspects of drug resistance, glucuronidation and drug transport into the cells, and help provide future strategies to tackle drug resistance in AML. (haematologica.org)

Dano, K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. (nature.com)
Purines: active transport by isolated choroid plexus. (uconn.edu)

It interferes with HIV capsid assembly, virus assembly and release, and nuclear transport. (uspharmacist.com)

Daklinza (daclatasvir) is a hepatitis C virus (HCV) NS5A inhibitor indicated for use with sofosbuvir for the treatment of chronic HCV genotype 3. (rxlist.com)
FDA-approved epidrugs for the treatment of cancer include DNA methyl transferases (DMNT)and histone deacetylase ( HDAC ) inhibitors. (whatisepigenetics.com)

Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle. (hal.science)

Anatomy7

Organisms2

Diseases2

Chemicals and Drugs74

Phenomena and Processes15

Information Science2

Protease inhibitors4

Analogs7

Substrates6

Dipyridamole3

Equilibrative Nucleoside Transporter3

Kinase5

Integrase1

NRTIs4

Adenosine3

Analogues8

Inhibition6

Uptake2

Nucleotide2

Antiviral5

Inhibits1

Proteins3

NNRTIs1

Transporters4

Monophosphate1

Renal2

Anthracyclines1

Substrate2

Vitro1

Analogue2

Antifolates1

Membranes1

Purine2

20231

Mechanism1

Membrane6

Selectively1

Drugs1

Enzymes2

Nucleotides2

Bind1

Derivatives1

Efflux1

Specificity1

Drug2

Active2

Nuclear1

Treatment2

Participates1