A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling.

abstract：:The gamma-aminobutyric acid(A) (GABA(A)) receptor contains a binding site (or sites) for benzodiazepines and related ligands. Previous studies have shown that the residue occupying position 101 (rat numbering) of the alpha subunit is particularly important in determining how some of these compounds interact with the r...

journal_title：Molecular pharmacology

authors： Dunn SM,Davies M,Muntoni AL,Lambert JJ

更新日期：1999-10-01 00:00:00

abstract：:Nitric oxide (NO) possesses potent anti-inflammatory properties; however, an over-production of NO will promote inflammation and induce cell and tissue dysfunction. Thus, the ability to precisely regulate NO production could prove beneficial in controlling damage. In this study, advantage was taken of the well charact...

journal_title：Molecular pharmacology

authors： Bian K,Harari Y,Zhong M,Lai M,Castro G,Weisbrodt N,Murad F

更新日期：2001-04-01 00:00:00

abstract：:The aim of the current study is to determine whether butein (3,4,2',4'-tetrahydroxychalcone) exhibits antiproliferative effects against tumor cells through suppression of the signal transducer and activator of transcription 3 (STAT3) activation pathway. We investigated the effects of butein on constitutive and inducib...

journal_title：Molecular pharmacology

authors： Pandey MK,Sung B,Ahn KS,Aggarwal BB

更新日期：2009-03-01 00:00:00

abstract：:The dissociation constants (Kd values) of substance P (SP), physalaemin, kassinin, and SP analogues acting on SP receptors in guinea pig ileal longitudinal muscle strips were determined by the pharmacological procedures of Furchgott [Adv. Drug Res. 3:21-55 (1966)]. This method involves analysis of the concentration-re...

journal_title：Molecular pharmacology

authors： Lin CW,Musacchio JM

更新日期：1983-05-01 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amn...

journal_title：Molecular pharmacology

authors： Berry EB,Eykholt R,Helliwell RJ,Gilmour RS,Mitchell MD,Marvin KW

更新日期：2003-12-01 00:00:00

abstract：:The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails to bind opioid ligands. We developed two radioligands for the OFQ-R: a tritiated native OFQ peptide ([3H]OFQ) an...

journal_title：Molecular pharmacology

authors： Ardati A,Henningsen RA,Higelin J,Reinscheid RK,Civelli O,Monsma FJ Jr

更新日期：1997-05-01 00:00:00

abstract：:The nucleoside analog 5-azacytidine is an archetypical drug for epigenetic cancer therapy, and its clinical effectiveness has been demonstrated in the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). However, therapy resistance in patients with MDS/AML remains a challenging issue. Mem...

journal_title：Molecular pharmacology

authors： Hummel-Eisenbeiss J,Hascher A,Hals PA,Sandvold ML,Müller-Tidow C,Lyko F,Rius M

更新日期：2013-09-01 00:00:00

abstract：:The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, and Actinomycin D were studied on purified mouse leukemia (L1210) DNA topoisomerases I and II. DNA unwinding and cross-linking were also studied. It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (...

journal_title：Molecular pharmacology

authors： Wassermann K,Markovits J,Jaxel C,Capranico G,Kohn KW,Pommier Y

更新日期：1990-07-01 00:00:00

abstract：:Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhanci...

journal_title：Molecular pharmacology

authors： McNabb HJ,Gonzalez S,Muli CS,Sjögren B

更新日期：2020-12-01 00:00:00

abstract：:The in vivo bioavailability of exogenous fibroblast growth factor 2 (FGF2) was studied after i.v. injection of uniformly 14C-labeled FGF2 into young rats. 14C-FGF2 was rapidly accumulated in almost all solid organs within 5 min. After 30 min, more than 65% of FGF2 was retained in liver, 4.5% in kidneys, 1.2% in spleen...

journal_title：Molecular pharmacology

authors： Colin S,Jeanny JC,Mascarelli F,Vienet R,Al-Mahmood S,Courtois Y,Labarre J

更新日期：1999-01-01 00:00:00

abstract：:The inflammatory response is necessary for the host's defense against pathogens; however, uncontrolled or unregulated production of eicosanoids has been associated with several types of chronic inflammatory diseases. Thus, it is not surprising that enzymes implicated in the production of eicosanoids have been strategi...

journal_title：Molecular pharmacology

authors： Doucet MS,Jougleux JL,Poirier SJ,Cormier M,Léger JL,Surette ME,Pichaud N,Touaibia M,Boudreau LH

更新日期：2019-01-01 00:00:00

abstract：:alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are recognized as the principal nicotine binding site in brain. Recombinant alpha4beta2 nAChR demonstrate biphasic concentration-response relationships with low- and high-EC50 components. This study shows that untranslated regions (UTR) can influence expression of...

journal_title：Molecular pharmacology

authors： Briggs CA,Gubbins EJ,Marks MJ,Putman CB,Thimmapaya R,Meyer MD,Surowy CS

更新日期：2006-07-01 00:00:00

abstract：:A high cytoplasmic Na(+) concentration may contribute to N-methyl-D-aspartate (NMDA)-induced excitotoxicity by promoting Ca(2+) influx via reverse operation of the Na(+)/Ca(2+) exchanger (NaCaX), but may simultaneously decrease the electrochemical Ca(2+) driving force by depolarizing the plasma membrane (PM). Digital ...

journal_title：Molecular pharmacology

authors： Kiedrowski L

更新日期：1999-09-01 00:00:00

abstract：:We investigated the mechanisms of MDR1 gene activation by CCAAT/enhancer binding protein beta (C/EBPbeta, or nuclear factor for interleukin 6) in human cancer cells. Transfection of the breast cancer cell line MCF-7 and its doxorubicin-selected variant MCF-7/ADR by either C/EBPbeta or C/EBPbeta-LIP (a dominant-negativ...

journal_title：Molecular pharmacology

authors： Chen KG,Sale S,Tan T,Ermoian RP,Sikic BI

更新日期：2004-04-01 00:00:00

abstract：:Voltage-gated sodium channels (Navs) are promising targets for analgesic and antiepileptic therapies. Although specificity between Nav subtypes may be desirable to target specific neural types, such as nociceptors in pain, many broadly acting Nav inhibitors are clinically beneficial in neuropathic pain and epilepsy. H...

journal_title：Molecular pharmacology

authors： Hinckley CA,Kuryshev Y,Sers A,Barre A,Buisson B,Naik H,Hajos M

更新日期：2021-01-01 00:00:00

abstract：:GH3 cells show spontaneous activity characterized by bursts of action potentials and oscillations in [Ca 2+]i. This activity is modulated by the activation of exogenously expressed opioid receptors. In GH3 cells expressing only micro receptors (GH3MOR cells), the micro receptor-specific ligand [D-Ala2,N-Me-Phe4,Gly5-o...

journal_title：Molecular pharmacology

authors： Charles AC,Mostovskaya N,Asas K,Evans CJ,Dankovich ML,Hales TG

更新日期：2003-01-01 00:00:00

abstract：:Notch-1 (Notch) is a cell surface receptor that regulates cell-fate decisions in the developing nervous system, and it may also have roles in synaptic plasticity in the adult brain. Binding of its ligands results in the proteolytic cleavage of Notch by the γ-secretase enzyme complex, thereby causing the release of a N...

journal_title：Molecular pharmacology

authors： Arumugam TV,Cheng YL,Choi Y,Choi YH,Yang S,Yun YK,Park JS,Yang DK,Thundyil J,Gelderblom M,Karamyan VT,Tang SC,Chan SL,Magnus T,Sobey CG,Jo DG

更新日期：2011-07-01 00:00:00

abstract：:Autophagy is the process by which cellular material is delivered to lysosomes for degradation and recycling. There are three different types of autophagy, but macroautophagy, which involves the formation of double membrane vesicles that engulf proteins and organelles that fuse with lysosomes, is by far the most studie...

journal_title：Molecular pharmacology

authors： Thorburn A,Thamm DH,Gustafson DL

更新日期：2014-06-01 00:00:00

abstract：:Histone deacetylase inhibitors (HDACis) are currently in trial or are in clinical use for the treatment of a number of tumor types. The clinical efficacy of HDACis can be partly attributed to the modulation of the cell cycle by the HDACis. Here, we have examined the effects of N-(2-aminophenyl)-4-((4-pyridin-3-ylpyrim...

journal_title：Molecular pharmacology

authors： Chia K,Beamish H,Jafferi K,Gabrielli B

更新日期：2010-09-01 00:00:00

abstract：:Nuclear receptors play important roles in the maintenance of the endocrine system, regulation of organ differentiation, and fetal development. Endocrine disruptors exert their adverse effects by disrupting the endocrine system via various mechanisms. To assess the effects of endocrine disruptors on nuclear receptors, ...

journal_title：Molecular pharmacology

authors： Kanayama T,Kobayashi N,Mamiya S,Nakanishi T,Nishikawa J

更新日期：2005-03-01 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：:Ro 11-2465 is a cyanide derivative of imipramine. In cerebral cortex homogenates, [3H] Ro 11-2465 displays a binding profile similar to that of [3H]imipramine. Agents compete with binding of [3H]Ro 11-2465 in an order of potency similar to their ability to block serotonin uptake, and raphe lesions greatly decrease the...

journal_title：Molecular pharmacology

authors： Dumbrille-Ross A,Tang SW

更新日期：1983-05-01 00:00:00

abstract：:Valproic acid (VPA) is a widely used antiepileptic agent that is undergoing clinical evaluation for anticancer therapy. We assessed the effects of VPA on angiogenesis in vitro and in vivo. In human umbilical vein endothelial cells, therapeutically relevant concentrations of VPA (0.25 to 1 mM) inhibited proliferation, ...

journal_title：Molecular pharmacology

authors： Michaelis M,Michaelis UR,Fleming I,Suhan T,Cinatl J,Blaheta RA,Hoffmann K,Kotchetkov R,Busse R,Nau H,Cinatl J Jr

更新日期：2004-03-01 00:00:00

abstract：:The deletion of Phe-508 (DeltaPhe508) constitutes the most prevalent of a number of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that cause cystic fibrosis (CF). This mutation leads to CFTR misfolding and retention in the endoplasmic reticulum, as well as impaired channel activity. The b...

journal_title：Molecular pharmacology

authors： Wellhauser L,Kim Chiaw P,Pasyk S,Li C,Ramjeesingh M,Bear CE

更新日期：2009-06-01 00:00:00

abstract：:Interleukin-2 (IL-2) is an immunoregulatory cytokine whose biological effects are mediated through interaction with specific receptors on the surface of target cells. Due to its presumed role in generating a normal immune response, IL-2 is being evaluated for the treatment of a variety of tumors, in addition to infect...

journal_title：Molecular pharmacology

authors： Chang DZ,Tasayco ML,Ciardelli TL

更新日期：1995-01-01 00:00:00

abstract：:Benzbromarone (BBR), a potent uricosuric agent for the management of gout, is known to cause fatal fulminant hepatitis. While the mechanism of BBR-induced idiosyncratic hepatotoxicity remains unelucidated, cytochrome P450 enzyme (CYP450)-mediated bioactivation of BBR to electrophilic reactive metabolites is commonly r...

journal_title：Molecular pharmacology

authors： Tang LWT,Verma RK,Fan H,Chan ECY

更新日期：2021-01-12 00:00:00

abstract：:Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...

journal_title：Molecular pharmacology

authors： Ekins S,Kholodovych V,Ai N,Sinz M,Gal J,Gera L,Welsh WJ,Bachmann K,Mani S

更新日期：2008-09-01 00:00:00

abstract：:Mitsuya and Broder [Proc. Natl. Acad. Sci. USA 83:1911-1915 (1986)] demonstrated that every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside containing the 2',3'-dideoxyribose configuration, when evaluated against human immunodeficiency virus (HIV) in vitro, significantly s...

journal_title：Molecular pharmacology

authors： Hao Z,Cooney DA,Hartman NR,Perno CF,Fridland A,DeVico AL,Sarngadharan MG,Broder S,Johns DG

更新日期：1988-10-01 00:00:00

abstract：:The binding affinities of 16 7-substituted 2,3-dichlorodibenzo-p-dioxins for the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cytosolic receptor protein from male Wistar rats have been determined. The EC50 value for each compound was estimated by competitive displacement of [3H]TCDD and the data illustrated that the dif...

journal_title：Molecular pharmacology

authors： Denomme MA,Homonoko K,Fujita T,Sawyer T,Safe S

更新日期：1985-06-01 00:00:00

abstract：:Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. CYP2E1 has also been implicated in alcohol liver disease because of its contribution to oxidative stress. Previously, polymorphic alleles with mutations in i...

journal_title：Molecular pharmacology

authors： Hu Y,Oscarson M,Johansson I,Yue QY,Dahl ML,Tabone M,Arincò S,Albano E,Ingelman-Sundberg M

更新日期：1997-03-01 00:00:00