Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There continues to be questions about the safety and effectiveness of Hydroxyurea since rigorous clinical trials have just begun. The mechanisms of the drug are not fully understood, but may include inhibition of DNA synthesis, potentiation of nucleoside reverse transcriptase inhibitor activity, enhancement of nucleoside phosphorylation, compensation for resistance to ddI, and modulation of the immune system. A table compares the results of several recent trials of Hydroxyurea treatment in combination with antiretrovirals. There is a discussion of how well Hydroxyurea works with ddI, other nucleosides, and whether it is best used in salvage or first-time treatment. More studies of Hydroxyurea are needed.
 ...
PMID:Is Hydroxyurea for real? 1136 31

An advisory committee of the Food and Drug Administration (FDA) has recommended accelerated approval for abacavir (ABC, Ziagen). The approval decision was not unanimous due to concerns of drug toxicity. Three percent of those taking the drug have developed severe allergic reactions, and at least eight people have died of complications related to the allergic reaction. Abacavir works by attacking the viral enzyme reverse transcriptase (RT), and it is related to other drugs such as AZT, 3TC, d4T, ddI, and ddC. Abacavir should be taken twice daily, in combination with other anti-HIV medications.
 ...
PMID:Abacavir gets green light from FDA advisory board. Food and Drug Administration. 1136 24

The experimental reverse transcriptase inhibitor FddA (lodenosine) has shown promise in early studies. The drug was originally developed by the National Cancer Institute (NCI) and appears to have little in vitro cross-resistance with other drugs in its class, including AZT (Retrovir), ddI (Videx), and d4T (Zerit). Drug trials are in the early stages, and there is limited data on the drug to date. The NCI is planning a Phase I/II trial. U.S. Bioscience is planning a Phase II trial to study FddA in combination with a protease inhibitor plus a nucleoside analog in treatment-naive patients. Contact information is provided.
 ...
PMID:FddA: antiretroviral in development. 1136 97

Current research findings and treatment issues related to a number of drugs are briefly outlined. Topics include T-20, a reformulation of ddI, PMPA, chicoric acid, Omniferon (alpha leukoferon), and Mepron. Also discussed is a non-nucleoside reverse transcriptase inhibitor called calanolide A, which is synthesized from a tree native to Malaysian rain forests. An update is provided on Panretin, a gel which is used to treat KS lesions. Contact information is provided.
 ...
PMID:Drug watch. 1136 39

Hydroxyurea (Hydrea) is an antiviral drug approved for use against cancer and sickle cell anemia. Produced by Bristol-Myers Squibb, it has not yet received Food and Drug Administration (FDA) approval for use against HIV; however, trial results are promising. The drug works by blocking a human cell enzyme used to multiply cells, and appears to be most effective when combined with reverse transcriptase inhibitors such as ddI or d4T. HIV does not develop resistance to hydroxyurea, and hydroxyurea can slow mutations in the virus. It is taken once or twice daily and is available in 500 mg tablets.
 ...
PMID:Hydroxyurea: what it is. New Mexico AIDS InfoNet. 1136 49

As part of our on-going study of the analysis and quantitation of anti-HIV nucleosides, a capillary electrochromatography (CEC) method has been developed for the simultaneous quantitation of nucleoside HIV reverse transcriptase inhibitors (NRTIs), i.e. zidovudine (AZT), lamivudine (3TC), didanosine (ddA) and its administrated form (ddI), stavudine (d4T) and hivid (ddC). CEC on chiral stationary phase has mainly been dedicated to the separation of enantiomers. However, this paper explores an original application of a beta-cyclodextrin-bonded silica packed column, taking advantage of the internal hydrophobicity of the polysaccharide to separate the NRTIs. The influence of several parameters (pH buffer, ionic strength, acetonitrile content, temperature and voltage) has been investigated using the short-end injection technique to achieve baseline separation in a short-time analysis before quantitation.
 ...
PMID:Simultaneous quantitation of nucleoside HIV-1 reverse transcriptase inhibitors by short-end injection capillary electrochromatography on a beta-cyclodextrin-bonded silica stationary phase. 1157 85

In an effort to elucidate a set of structure-activity relationships in the alkenyldiarylmethane (ADAM) series of non-nucleoside reverse transcriptase inhibitors, a number of modifications were made at two locations: (1) the meta positions of the two aromatic rings and (2) the end of the alkenyl chain. Forty-two new ADAMs were synthesized and evaluated for inhibition of the cytopathic effect of HIV-1(RF) in CEM-SS cell culture and for inhibition of HIV-1 reverse transcriptase. The size of the aromatic substituents was found to affect anti-HIV activity, with optimal activity appearing with Cl, CH(3), and Br substituents and with diminished activity occurring with smaller (H and F) or larger (I and CF(3)) substituents. The substituents at the end of the alkenyl chain were also found to influence the antiviral activity, with maximal activity associated with methyl or ethyl ester groups and with diminished activity resulting from substitution with higher esters, amides, sulfides, sulfoxides, sulfones, thioesters, acetals, ketones, carbamates, ureas, and thioureas. Twelve of the new ADAMs displayed submicromolar EC(50) values for inhibition of the cytopathic effect of HIV-1(RF) in CEM-SS cells. Selected ADAMs, 19 and 21, were compared to previously published ADAMs 15 and 17 for antiviral efficacy and activity against the HIV-1 reverse transcriptase enzyme. All four ADAMs were found to inhibit HIV-1 reverse transcriptase enzyme activity, to inhibit the replication of a variety of HIV-1 clinical isolates representing syncytium-inducing, nonsyncytium-inducing, and subtype representative isolates, and to inhibit HIV-1 replication in monocytes. Subsequent assessment against a panel of site-directed reverse transcriptase mutants in NL4-3 demonstrated no effect of the K103N mutation on antiviral efficacy and a slight enhancement (6- to 11-fold) in sensitivity to AZT-resistant viruses. Additionally, ADAMs 19 (44-fold) and 21 (29-fold) were more effective against the A98G mutation (found in association with nevirapine resistance in vitro), and ADAM 21 was 5-fold and 2-fold more potent against the Y181C inactivation mutation than the previously reported ADAMs 15 and 17, respectively. All four ADAMs were tested for efficacy against a multidrug-resistant virus derived from a highly experienced patient expressing resistance to the reverse transcriptase enzyme inhibitors AZT, ddI, 3TC, d4T, foscarnet, and nevirapine, as well as the protease inhibitors indinavir, saquinavir, and nelfinavir. ADAM 21 was 2-fold more potent than ADAM 15 and 6-fold more potent than ADAMs 17 and 19 at preventing virus replication. Thus, we have identified a novel series of reverse transcriptase inhibitors with a favorable profile of antiviral activity against the primary mutation involved in clinical failure of non-nucleoside reverse transcriptase inhibitors, K103N, and that retain activity against a multidrug-resistant virus.
 ...
PMID:The biological effects of structural variation at the meta position of the aromatic rings and at the end of the alkenyl chain in the alkenyldiarylmethane series of non-nucleoside reverse transcriptase inhibitors. 1170 13

Clinical studies with tenofovir disoproxil fumarate, an oral prodrug of the nucleotide analog tenofovir, recently approved for the treatment of HIV, have demonstrated antiviral activity and good tolerability in HIV-infected patients. In order to better understand the cytotoxicity profile of tenofovir relative to the other nucleoside reverse transcriptase inhibitors (NRTIs), the in vitro effects of these agents were evaluated in various human cell types. Tenofovir inhibited the proliferation of liver-derived HepG2 cells and normal skeletal muscle cells with CC(50) values of 398 and 870 microM, respectively. In comparison, ZDV, ddC, ddI, d4T, and abacavir all showed lower CC(50) values in these two cell types. Evaluation of hematopoietic toxicity revealed that tenofovir was less cytotoxic towards erythroid progenitor cells (CC(50)>200 microM) than ZDV, d4T, and ddC (CC(50)=0.06-5 microM). Despite some degree of donor-to-donor variability, the inhibitory activity of the tested NRTIs against myeloid cell lineage, in the order of decreasing severity, was consistently ddC>ZDV>d4T>tenofovir>3TC. Finally, tenofovir showed substantially weaker effects on proliferation and viability of renal proximal tubule epithelial cells than cidofovir, a related nucleotide analog with the potential to induce renal tubular dysfunction. In conclusion, tenofovir exhibited weak cytotoxic effects in all cell types tested with less in vitro cytotoxicity than the majority of NRTIs currently used for the treatment of HIV disease.
 ...
PMID:Tenofovir exhibits low cytotoxicity in various human cell types: comparison with other nucleoside reverse transcriptase inhibitors. 1188 56

As part of our on-going study of the analysis of anti-human immunodeficiency virus (HIV) nucleosides, a capillary electrochromatography (CEC) method has been developed for the concurrent analysis of nucleoside HIV reverse transcriptase inhibitors (NRTIs) in a pool of endogenous nucleosides. Up to now, beta-cyclodextrin-bonded silica stationary phases have mainly been dedicated to the separation of enantiomers; however, these polysaccharides can be also be used in achiral way. This work aims at showing how CEC performed on a beta-cyclodextrin-bonded silica stationary phase can be used to concurrently resolve zidovudine (AZT), lamivudine (3TC), didanosine (ddA) and its administrated form (ddI), stavudine (d4T) and hivid (ddC) in a mixture of adenosine (A), cytidine (C), guanosine (G), thymidine (T) and uridine (U). The influence of several parameters (pH buffer, ionic strength, acetonitrile content, temperature and voltage) on both the retention times and the retention factors has been investigated using the short-end injection technique to achieve baseline separation in a short-time analysis before quantitation. Moreover, the retention factors of the charged solutes in short-end injection-CEC were calculated using theoretically derived equations, allowing for the actual voltage drop in the packed section of the semipacked CEC capillary.
 ...
PMID:Concurrent analysis of nucleoside reverse transcriptase inhibitors in a pool of endogenous nucleosides by short-end injection-capillary electrochromatography on a beta-cyclodextrin-bonded stationary phase. 1200 25

An active metabolite, ddATP, of didanosine that is an analogue of purine-nucleoside (a component of nucleic acid) was known to inhibit the activity of DNA polymerase for E. coli. In 1985, Dr. Michiya et al. of NCI reported that didanosine and ddA inhibited replication of the human immunodeficiency virus (HIV). This discovery led to the clinical application of both the compounds. Didanosine, after being uptaken into a cell, becomes an active metabolite, ddATP, to inhibit a reverse transcriptase of HIV. Compared with zidovudine, didanosine has weak cytotoxicity both in vitro and in vivo. Didanosine, which is recommended as a first-line therapy drug in the Japanese Guideline on an anti-HIV Infection Therapy, was approved as twice-daily Videx Tablet and Dry Syrup formulations for launch in June 1992. In March 2001, a once-daily Videx EC Capsule formulation was approved and launched, having expected adherence improvements in HIV/AIDS patients.
 ...
PMID:[Pharmacological and clinical properties of didanosine (VIDEX), a nucleoside reverse transcriptase inhibitor]. 1218 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>