abstract：:Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion protein can exert an anti-inflammatory effect. To investigate the mechanism by which GITR-Fc exerts its effects, we first used GITR knock-out (GITR(-/-)) mic...

journal_title：Molecular pharmacology

authors： Nocentini G,Cuzzocrea S,Genovese T,Bianchini R,Mazzon E,Ronchetti S,Esposito E,Rosanna DP,Bramanti P,Riccardi C

更新日期：2008-06-01 00:00:00

abstract：:Inhibition of cathepsin C, a dipeptidyl peptidase that activates many serine proteases, represents an attractive therapeutic strategy for inflammatory diseases with a high neutrophil burden. We recently showed the feasibility of blocking the activation of neutrophil elastase, cathepsin G, and proteinase-3 with a singl...

journal_title：Molecular pharmacology

authors： Méthot N,Guay D,Rubin J,Ethier D,Ortega K,Wong S,Normandin D,Beaulieu C,Reddy TJ,Riendeau D,Percival MD

更新日期：2008-06-01 00:00:00

abstract：:Allosteric modulators of G-protein-coupled receptors can regulate conformational states involved in receptor activation ( Mol Pharmacol 58: 1412-1423, 2000 ). This hypothesis was investigated for the corticotropin-releasing factor type 1 (CRF(1)) receptor using a novel series of ligands with varying allosteric effect ...

journal_title：Molecular pharmacology

authors： Hoare SR,Fleck BA,Gross RS,Crowe PD,Williams JP,Grigoriadis DE

更新日期：2008-05-01 00:00:00

abstract：:Reversal of the multidrug-resistant (MDR) phenotype is very important for chemotherapy success. In fact, the expression of the MDR1 gene-encoded P-glycoprotein (P-gp) actively expels antitumor agents such as daunomycin (DNM) out of the cells, resulting in drug resistance. We show that upon conjugation to triplex-formi...

journal_title：Molecular pharmacology

authors： Stierlé V,Duca M,Halby L,Senamaud-Beaufort C,Capobianco ML,Laigle A,Jollès B,Arimondo PB

更新日期：2008-05-01 00:00:00

abstract：:Regulator of G protein signaling (RGS) proteins accelerate the endogenous GTPase activity of Galpha(i/o) proteins to increase the rate of deactivation of active Galpha-GTP and Gbetagamma signaling molecules. Previous studies have suggested that RGS proteins are more effective on less efficiently coupled systems such a...

journal_title：Molecular pharmacology

authors： Clark MJ,Linderman JJ,Traynor JR

更新日期：2008-05-01 00:00:00

abstract：:Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subt...

journal_title：Molecular pharmacology

authors： Fernandez D,Sargent J,Sachse FB,Sanguinetti MC

更新日期：2008-04-01 00:00:00

abstract：:We have studied the mechanism of action of Arg(*)-Arg-Nal(2)-Cys(1x)-Tyr-Gln-Lys-(d-Pro)-Pro-Tyr-Arg-Cit-Cys(1x)-Arg-Gly-(d-Pro)(*) (POL3026), a novel specific beta-hairpin mimetic CXC chemokine receptor (CXCR)4 antagonist. POL3026 specifically blocked the binding of anti-CXCR4 monoclonal antibody 12G5 and the intrace...

journal_title：Molecular pharmacology

authors： Moncunill G,Armand-Ugón M,Clotet-Codina I,Pauls E,Ballana E,Llano A,Romagnoli B,Vrijbloed JW,Gombert FO,Clotet B,De Marco S,Esté JA

更新日期：2008-04-01 00:00:00

abstract：:The nonselective cation channel TRPA1 (ANKTM1, p120) is a potential mediator of pain, and selective pharmacological modulation of this channel may be analgesic. Although several TRPA1 activators exist, these tend to be either reactive or of low potency and/or selectivity. The aim of the present study, therefore, was t...

journal_title：Molecular pharmacology

authors： Maher M,Ao H,Banke T,Nasser N,Wu NT,Breitenbucher JG,Chaplan SR,Wickenden AD

更新日期：2008-04-01 00:00:00

abstract：:Ubiquitination of the human kappa opioid receptor (hKOR) expressed in Chinese hamster ovary (CHO) cells was observed in the presence of the proteasomal inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) and enhanced by the agonists (-)(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny) cyclohexyl] benzeneaceta...

journal_title：Molecular pharmacology

authors： Li JG,Haines DS,Liu-Chen LY

更新日期：2008-04-01 00:00:00

abstract：:Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common malignancies worldwide, with low 5-year survival rates. Current strategies that block epidermal growth factor receptor (EGFR) have limited effects when administered as single agents. Targeting EGFR via intratumoral administration of phospho...

journal_title：Molecular pharmacology

authors： Thomas SM,Ogagan MJ,Freilino ML,Strychor S,Walsh DR,Gooding WE,Grandis JR,Zamboni WC

更新日期：2008-03-01 00:00:00

abstract：:Anthracyclines are effective anticancer agents. However, their use is limited by cardiotoxicity, an effect linked to their ability to chelate iron and to perturb iron metabolism (Mol Pharmacol 68:261-271, 2005). These effects on iron-trafficking remain poorly understood, but they are important to decipher because trea...

journal_title：Molecular pharmacology

authors： Xu X,Sutak R,Richardson DR

更新日期：2008-03-01 00:00:00

abstract：:The initial event upon binding of insulin-like growth factor 1 to the insulin-like growth factor type-I receptor (IGF-1R) is auto-phosphorylation of tyrosine residues within the activation loop of the kinase domain followed by phosphorylation of other receptor tyrosine residues and the subsequent activation of the int...

journal_title：Molecular pharmacology

authors： Vasilcanu R,Vasilcanu D,Sehat B,Yin S,Girnita A,Axelson M,Girnita L

更新日期：2008-03-01 00:00:00

abstract：:The retinoid-related orphan receptors (RORs) and liver X receptors (LXRs) were postulated to have distinct functions. RORs play a role in tissue development and circadian rhythm, whereas LXRs are sterol sensors that affect lipid homeostasis. In this study, we revealed a novel function of RORalpha (NR1F1) in regulating...

journal_title：Molecular pharmacology

authors： Wada T,Kang HS,Angers M,Gong H,Bhatia S,Khadem S,Ren S,Ellis E,Strom SC,Jetten AM,Xie W

更新日期：2008-03-01 00:00:00

abstract：:Previous biochemical studies have demonstrated that synergy between non-nucleoside reverse transcriptase (RT) inhibitors (NNRTI) and nucleoside RT inhibitors (NRTIs) is due to inhibition by the NNRTI of the rate at which HIV-1 RT facilitates ATP-mediated excision of NRTIs from chain-terminated template/primers (T/P). ...

journal_title：Molecular pharmacology

authors： Radzio J,Sluis-Cremer N

更新日期：2008-02-01 00:00:00

abstract：:Inflammation contributes to pain hypersensitivity through multiple mechanisms. Among the most well characterized of these is the sensitization of primary nociceptive neurons by arachidonic acid metabolites such as prostaglandins through G protein-coupled receptors. However, in light of the recent discovery that the no...

journal_title：Molecular pharmacology

authors： Taylor-Clark TE,Undem BJ,Macglashan DW Jr,Ghatta S,Carr MJ,McAlexander MA

更新日期：2008-02-01 00:00:00

abstract：:The present study characterizes the methanethiosulfonate (MTS) inhibition profiles of 26 consecutive cysteine-substituted mutants comprising transmembrane (TM) helix 6 of the human apical Na(+)-dependent bile acid transporter (SLC10A2). TM6 is linked exofacially to TM7 via extracellular loop 3. TM7 was identified prev...

journal_title：Molecular pharmacology

authors： Hussainzada N,Khandewal A,Swaan PW

更新日期：2008-02-01 00:00:00

abstract：:Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels encoded by the Slo1 gene are ubiquitously expressed, and they play a role in regulation of many cell types. In excitable cells, BK(Ca) channels and voltage-activated Ca(2+) channels often form functional complexes that allow the cytoplasmic domains of BK(Ca) ch...

journal_title：Molecular pharmacology

authors： Zou S,Jha S,Kim EY,Dryer SE

更新日期：2008-02-01 00:00:00

abstract：:A novel cloned polymorphism of the human concentrative nucleoside transporter hCNT3 was described and functionally characterized. This variant consists of a T/C transition leading to the substitution of cysteine 602 by an arginine residue in the core of transmembrane domain 13. The resulting hCNT3(C602R) protein has t...

journal_title：Molecular pharmacology

authors： Errasti-Murugarren E,Cano-Soldado P,Pastor-Anglada M,Casado FJ

更新日期：2008-02-01 00:00:00

abstract：:The aim of this study was to create and characterize constitutively active mutant (CAM) histamine H(1) receptors (H(1)R) using random mutagenesis methods to further investigate the activation process of the rhodopsin-like family of G protein-coupled receptors (GPCRs). This approach identified position 6.40 in TM 6 as ...

journal_title：Molecular pharmacology

authors： Bakker RA,Jongejan A,Sansuk K,Hacksell U,Timmerman H,Brann MR,Weiner DM,Pardo L,Leurs R

更新日期：2008-01-01 00:00:00

abstract：:Dynamin is a GTPase enzyme involved in membrane constriction and fission during endocytosis. Phospholipid binding via its pleckstrin homology domain maximally stimulates dynamin activity. We developed a series of surface-active small-molecule inhibitors, such as myristyl trimethyl ammonium bromide (MiTMAB) and octadec...

journal_title：Molecular pharmacology

authors： Quan A,McGeachie AB,Keating DJ,van Dam EM,Rusak J,Chau N,Malladi CS,Chen C,McCluskey A,Cousin MA,Robinson PJ

更新日期：2007-12-01 00:00:00

abstract：:Prior studies indicate that adenosine and the adenosine A2A receptor play a role in hepatic fibrosis by a mechanism that has been proposed to involve direct stimulation of hepatic stellate cells (HSCs). The objective of this study was to determine whether primary hepatic stellate cells produce collagen in response to ...

journal_title：Molecular pharmacology

authors： Che J,Chan ES,Cronstein BN

更新日期：2007-12-01 00:00:00

abstract：:The cytolytic ionotropic ATP receptor P2X7 has several important roles in immune cell regulation, such as cytokine release, apoptosis, and microbial killing. Although P2X7 receptors are frequently coexpressed with another subtype of P2X receptor, P2X4, they are believed not to form heteromeric assemblies but to functi...

journal_title：Molecular pharmacology

authors： Guo C,Masin M,Qureshi OS,Murrell-Lagnado RD

更新日期：2007-12-01 00:00:00

abstract：:Resveratrol (RES), a natural plant polyphenol, has gained interest as a nontoxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7,...

journal_title：Molecular pharmacology

authors： Sareen D,Darjatmoko SR,Albert DM,Polans AS

更新日期：2007-12-01 00:00:00

abstract：:The synthetic alpha-conotoxin Vc1.1 is a small disulfide bonded peptide currently in development as a treatment for neuropathic pain. Unlike Vc1.1, the native post-translationally modified peptide vc1a does not act as an analgesic in vivo in rat models of neuropathic pain. It has recently been proposed that the primar...

journal_title：Molecular pharmacology

authors： Nevin ST,Clark RJ,Klimis H,Christie MJ,Craik DJ,Adams DJ

更新日期：2007-12-01 00:00:00

abstract：:15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a cyclopentenonic prostaglandin endowed with powerful anti-inflammatory activities, as shown in animal models of inflammatory/autoimmune diseases, where pharmacological administration of this prostanoid can ameliorate inflammation and local tissue damage via act...

journal_title：Molecular pharmacology

authors： Fionda C,Nappi F,Piccoli M,Frati L,Santoni A,Cippitelli M

更新日期：2007-11-01 00:00:00

abstract：:The ubiquitously expressed nitric oxide (NO) receptor soluble guanylate cyclase (sGC) plays a key role in signal transduction. Binding of NO to the N-terminal prosthetic heme moiety of sGC results in approximately 200-fold activation of the enzyme and an increased conversion of GTP into the second messenger cGMP. sGC ...

journal_title：Molecular pharmacology

authors： Rothkegel C,Schmidt PM,Atkins DJ,Hoffmann LS,Schmidt HH,Schröder H,Stasch JP

更新日期：2007-11-01 00:00:00

abstract：:The bisdioxopiperazines such as (+)-(S)-4,4'-propylenedi-2,6-piperazinedione (dexrazoxane; ICRF-187), 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), and 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione (ICRF-193) are agents that inhibit eukaryotic topoisomerase II, whereas their ring-opened hydrolysis pro...

journal_title：Molecular pharmacology

authors： Grauslund M,Thougaard AV,Füchtbauer A,Hofland KF,Hjorth PH,Jensen PB,Sehested M,Füchtbauer EM,Jensen LH

更新日期：2007-10-01 00:00:00

abstract：:The effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of the phytoestrogens daidzein, genistein, and coumestrol was investigated using Bcrp(-/-) mice. Expression of the genes for either mouse Bcrp or human BCRP in MDCK II cells induced apically directed transport of the three phytoestrogens, w...

journal_title：Molecular pharmacology

authors： Enokizono J,Kusuhara H,Sugiyama Y

更新日期：2007-10-01 00:00:00

abstract：:Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels play an important role in the regulation of cell physiology in a wide variety of excitable and nonexcitable tissues. Filamin A is a conserved and ubiquitous actin-binding protein that forms perpendicular actin cross-links and contributes to changes in cell shap...

journal_title：Molecular pharmacology

authors： Kim EY,Ridgway LD,Dryer SE

更新日期：2007-09-01 00:00:00

abstract：:Nicotine biotransformation affects the smoking habits of addicted individuals and therefore their health risk. Using an improved analytical method, we have discovered that the human UDP-glucuronosyltransferase (UGT) 2B10, a liver enzyme previously unknown to conjugate nicotine or exhibit considerable activity toward a...

journal_title：Molecular pharmacology

authors： Kaivosaari S,Toivonen P,Hesse LM,Koskinen M,Court MH,Finel M

更新日期：2007-09-01 00:00:00

abstract：:2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T ce...

journal_title：Molecular pharmacology

authors： Román J,de Arriba AF,Barrón S,Michelena P,Giral M,Merlos M,Bailón E,Comalada M,Gálvez J,Zarzuelo A,Ramis I

更新日期：2007-08-01 00:00:00

abstract：:ATM and NBS1, mutation of which lead to the human autosomal recessive diseases ataxia telangiectasia and Nijmegen breakage syndrome (NBS), respectively, are essential elements in the cellular response to DNA damage induced by ionizing radiation (IR). ATM is a member of the phosphatidylinositol 3-kinase family and is a...

journal_title：Molecular pharmacology

authors： Cariveau MJ,Tang X,Cui XL,Xu B

更新日期：2007-08-01 00:00:00

abstract：:Recent clinical studies reveal that selective agonists of group II metabotropic glutamate (mGlu) receptors have robust efficacy in treating positive and negative symptoms in patients with schizophrenia. Group II mGlu receptor agonists also modulate the in vivo activity of psychotomimetic drugs and reduce the ability o...

journal_title：Molecular pharmacology

authors： Benneyworth MA,Xiang Z,Smith RL,Garcia EE,Conn PJ,Sanders-Bush E

更新日期：2007-08-01 00:00:00

abstract：:Autophagy is a response of cancer cells to various anticancer therapies. It is designated as programmed cell death type II and characterized by the formation of autophagic vacuoles in the cytoplasm. The Akt/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) and the extracellular signal-regul...

journal_title：Molecular pharmacology

authors： Aoki H,Takada Y,Kondo S,Sawaya R,Aggarwal BB,Kondo Y

更新日期：2007-07-01 00:00:00

abstract：:Controlled inhibition of brain acetyl- and butyrylcholinesterases (AChE and BChE, respectively) and of monoamine oxidase-B (MAO-B) may slow neurodegeneration in Alzheimer's and Parkinson's diseases. It was postulated that certain carbamate esters would inhibit AChE and BChE with the concomitant release in the brain of...

journal_title：Molecular pharmacology

authors： Groner E,Ashani Y,Schorer-Apelbaum D,Sterling J,Herzig Y,Weinstock M

更新日期：2007-06-01 00:00:00

abstract：:Serotonin 5-HT(2B) receptors are often coexpressed with 5-HT(1B) receptors, and cross-talk between the two receptors has been reported in various cell types. However, many mechanistic details underlying 5-HT(1B) and 5-HT(2B) receptor cross-talk have not been elucidated. We hypothesized that 5-HT(2B) and 5-HT(1B) recep...

journal_title：Molecular pharmacology

authors： Janoshazi A,Deraet M,Callebert J,Setola V,Guenther S,Saubamea B,Manivet P,Launay JM,Maroteaux L

更新日期：2007-06-01 00:00:00

abstract：:As a member of the transient receptor potential (TRP) ion channel superfamily, the ligand-gated ion channel TRPA1 has been implicated in nociceptive function and pain states. The endogenous ligands that activate TRPA1 remain unknown. However, various agonists have been identified, including environmental irritants (e....

journal_title：Molecular pharmacology

authors： Niforatos W,Zhang XF,Lake MR,Walter KA,Neelands T,Holzman TF,Scott VE,Faltynek CR,Moreland RB,Chen J

更新日期：2007-05-01 00:00:00

abstract：:Many cellular signaling pathways share regulation by protein phosphatase-2A (PP2A), a widely expressed serine/threonine phosphatase, and the heterotrimeric G protein Galpha(12). PP2A activity is altered in carcinogenesis and in some neurodegenerative diseases. We have identified binding of Galpha(12) with the Aalpha s...

journal_title：Molecular pharmacology

authors： Zhu D,Tate RI,Ruediger R,Meigs TE,Denker BM

更新日期：2007-05-01 00:00:00

abstract：:Type II DNA topoisomerases are targets of acridine drugs. Nine mutations conferring resistance to acridines were obtained by forced molecular evolution, using methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide (mAMSA), methyl N-(4'-(9-acridinylamino)-2-methoxy-phenyl) carbamate hydrochloride (mAMCA)...

journal_title：Molecular pharmacology

authors： Leontiou C,Watters GP,Gilroy KL,Heslop P,Cowell IG,Craig K,Lightowlers RN,Lakey JH,Austin CA

更新日期：2007-04-01 00:00:00

abstract：:Tumor suppressor gene BRCA1 is frequently mutated in familial breast and ovarian cancer. BRCA1 plays pivotal roles in maintaining genomic stability by interacting with numerous proteins in cell cycle control and DNA repair. Irofulven (6-hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863) is one of a new class of anti...

journal_title：Molecular pharmacology

authors： Wiltshire T,Senft J,Wang Y,Konat GW,Wenger SL,Reed E,Wang W

更新日期：2007-04-01 00:00:00