Abstract：
:Recently, several classes of compounds have been shown to be potent, selective, and specific inhibitors of human immunodeficiency virus type 1 replication in vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Both the TIBO and HEPT derivatives specifically inhibit human immunodeficiency virus type 1 reverse transcriptase (RT). From a comparative study of the characteristics of RT inhibition by TIBO and HEPT, and from the competition between TIBO and HEPT for RT inhibition, we infer that both classes of compounds, although structurally unrelated, are targeted at the same site of the enzyme. Detailed functional and kinetic analyses indicate that this target site is functionally and possibly also spatially related to the substrate binding site.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Debyser Z,Pauwels R,Baba M,Desmyter J,De Clercq Ekeywords:
subject
Has Abstractpub_date
1992-05-01 00:00:00pages
963-8issue
5eissn
0026-895Xissn
1521-0111journal_volume
41pub_type
杂志文章abstract：:The interactions between beta-adrenergic receptor (beta AR) antagonists and the beta(2)AR were studied with the use of photoaffinity labels. A proteolytic map of the receptor was made and confirmed through amino-terminal amino acid sequencing by locating sites of derivatization. [125I]Iodoazidothiophenylalprenolol (IA...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) are ubiquitously expressed in the mammalian central nervous system, where they exert trophic actions on both neuronal and glial cells. However, the acute actions of PDGF on synaptic transmission are unknown. We report a novel regulatory action of PDGF/P...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Nitric oxide (NO) binds with high affinity to the heme of soluble guanylyl cyclase (sGC), resulting in accumulation of the second messenger cGMP in many biological systems. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) was recently described as potent and selective inhibitor of sGC, providing an invaluable tool wi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:The ability of four antidepressant drugs, imipramine, alaproclate, norzimelidine, and fluvoxamine, to inhibit serotonin transport into platelet plasma membrane vesicles was tested over a range of external Na+ concentrations. Imipramine affinity, as we previously reported [J. Biol. Chem. 258:6115-6119 (1983)] increases...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:The successful synthesis of dolastatin 11, a depsipeptide originally isolated from the mollusk Dolabella auricularia, permitted us to study its effects on cells. The compound arrested cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network. In a dose-and time-dependent ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.3.462
更新日期：2001-03-01 00:00:00
abstract：:The UGT1 locus is felt to be highly conserved between species, as is evident from the characterization of the locus in rodents and humans. In rabbits, cDNAs encoding proteins homologous to human UGT1A4, UGT1A6, and UGT1A7 have previously been identified. Here we demonstrate by Southern blot analysis, using exon 1 dive...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.1.89
更新日期：2000-07-01 00:00:00
abstract：:(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted enzymatically to BH4 within cells, also increased PC12 cell prolifer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Smooth muscle preparations of human aorta or pig coronary arteries contain nearly equal amounts of cGMP-dependent protein kinase isozymes (cGMP kinase I alpha and I beta). In order to understand the roles of these isozymes in relaxing vascular smooth muscle, several new cGMP analogs were synthesized and tested for pot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regu...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.116.107839
更新日期：2017-09-01 00:00:00
abstract：:Electron affinities, approximated by lowest unoccupied molecular orbital (LUMO) energies, were determined for an extensive group of nitrated polycyclic aromatic hydrocarbons by ab initio methods at the STO-3G level. Significant correlations were demonstrated between nitroarene LUMO energy and the corresponding mutagen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:When expressed via an inducible promoter in human embryonic kidney 293 cells, the rat Mas-related gene D (rMrgD) receptor responded to beta-alanine but not L-alanine by elevating intracellular [Ca(2+)], stimulating phosphorylation of the mitogenactivated protein kinases known as extracellular signal-regulated kinase (...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.018788
更新日期：2006-02-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with constitutive activities and those induced by xenobiotic ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One unexplained cellular role for the AHR is its ability to promote cell cycle progression in the absence of exogenous...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.059675
更新日期：2010-02-01 00:00:00
abstract：:Vinflunine, the newest fluorinated Vinca alkaloid, currently in phase III clinical trials, targets the microtubule network to induce mitotic block and apoptosis by mechanisms that remain unclear. In the current study, we investigated the apoptotic pathways induced by a wide range of vinflunine concentrations in SK-N-S...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.66.3.
更新日期：2004-09-01 00:00:00
abstract：:Reuptake of glutamate in astrocytes, a critical mechanism involved in the maintenance of physiological excitatory amino acid neurotransmission, is inhibited by both arachidonic acid (AA) and reactive oxygen species (ROS), via incompletely defined molecular mechanisms. Because ROS are generated during AA metabolism and...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:We studied the mechanism by which the peptide omega-grammotoxin-SIA inhibits voltage-dependent calcium channels. Grammotoxin at concentrations of > 50 nM completely inhibited inward current carried by 2 mM barium through P-type channels in rat cerebellar Purkinje neurons when current was elicited by depolarizations up...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.6.1095
更新日期：1997-12-01 00:00:00
abstract：:An opioid-like receptor has been cloned by several groups of researchers and recently shown to be activated by an endogenous heptadecapeptide termed orphanin FQ (or nociceptin). We isolated the corresponding mouse cDNA and coexpressed it in Xenopus laevis oocytes with the potassium channel subunits Kir3.1 (GIRK1) and ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Isoform-specific expression of endothelin-converting enzyme (ECE)-1, the major big endothelin-processing enzyme, is controlled by alternative promoters. Signaling pathways and transcriptional mechanisms of ECE-1 mRNA expression are largely unknown. To investigate ECE-1 isoform expression after protein kinase C (PKC) a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.6.1332
更新日期：2001-12-01 00:00:00
abstract：:Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer's disease. Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term pote...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.082891
更新日期：2013-04-01 00:00:00
abstract：:Telomerase activity is expressed in most types of cancer cells but not in normal somatic cells, suggesting that telomerase may be an important target for cancer chemotherapy. Inhibition of telomerase results in telomere erosion, leading to the subsequent growth arrest of cancer cells followed by senescence or cell dea...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.5.1117
更新日期：2003-05-01 00:00:00
abstract：:SR33557 belongs to a new class of molecules (indolizinsulfones) that act on the same receptor complex that has been characterized for other classical calcium channel effectors. The main binding properties of SR33557 to rabbit skeletal muscle are as follows. (i) Unlabeled SR33557 completely inhibits the specific bindin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:Adult guinea pig hippocampal membranes contain two 5-hydroxytryptamine (5-HT) receptors positively coupled with an adenylate cyclase. One is a typical 5-HT1A receptor and the second is a nonclassical 5-HT receptor that we previously proposed to call 5-HT4. Here, we show that 4-amino-5-chlor-2-methoxy-benzamide derivat...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphosphoinositide hydrolysis, was studied in thyroid cells. Incubation of cultured dog thyroid cells with 10 microM carbachol for 2-4 hr reduced the subsequent thyrotropic hormone (TSH) stimulation of adenylyl cyclase activity ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Nicotine can enhance working memory and attention. Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated in these processes. The ability of presynaptic nAChRs to modulate neurotransmitter release, notably glutamate release, is postulated to...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.046623
更新日期：2008-08-01 00:00:00
abstract：:The aim of this study was to clarify the mechanism by which cytochrome P450 (P450)-mediated catalytic activity is decreased following interferon (IFN) administration. Microsomal steroid hydroxylation was assessed to test the hypothesis that IFN selectively decreases the activities of individual P450 isozymes in male r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:Cannabinoids have been implicated in the reduction of glioma growth. The present study investigated a possible relationship between the recently shown induction of cyclooxygenase (COX)-2 expression by the endocannabinoid analog R(+)methanandamide [R(+)-MA] and its effect on the viability of H4 human neuroglioma cells....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.002618
更新日期：2004-12-01 00:00:00
abstract：:Merbarone (5-[N-phenyl carboxamido]-2-thiobarbituric acid) is an anticancer drug that inhibits the catalytic activity of DNA topoisomerase II (topo II) without damaging DNA or stabilizing DNA-topo II cleavable complexes. Although the cytotoxicity of the complex-stabilizing DNA-topo II inhibitors such as VP-16 (etoposi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-03-01 00:00:00
abstract：:Cell-penetrating peptides are amphipathic or cationic oligopeptides able to transport covalently attached cargoes across cell membranes. Peptide aptamers are polypeptide fragments of endogenous proteins that mimic and thus perturb interactions with other cellular proteins. Combining aptamer and CPP technology can gene...
journal_title：Molecular pharmacology
pub_type： 评论,杂志文章
doi：10.1124/mol.105.011429
更新日期：2005-04-01 00:00:00
abstract：:The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine C...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:The relationship between receptor number and agonist-induced intracellular responses has been well studied in receptors coupled to adenylate cyclase; however, for receptors coupled to phospholipase C (PLC), very little is known about the effect of receptor number on receptor-mediated processes. To explore this issue, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.5.721
更新日期：1997-05-01 00:00:00
