abstract：:Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidy...

journal_title：Molecular pharmacology

authors： Tang R,Gao L,Kawatani M,Chen J,Cao X,Osada H,Xiang L,Qi J

更新日期：2015-08-01 00:00:00

abstract：:Thrombin, the key effector protease of the coagulation cascade, drives fibrin deposition and activates human platelets through protease-activated receptor-1 (PAR1). These processes are critical to the progression of thrombotic diseases. Thrombin is the main target of anticoagulant therapy, and major efforts have led t...

journal_title：Molecular pharmacology

authors： Chen B,Soto AG,Coronel LJ,Goss A,van Ryn J,Trejo J

更新日期：2015-07-01 00:00:00

abstract：:Mitochondrial disorders are devastating genetic diseases for which efficacious therapies are still an unmet need. Recent studies report that increased availability of intracellular NAD obtained by inhibition of the NAD-consuming enzyme poly(ADP-ribose) polymerase (PARP)-1 or supplementation with the NAD-precursor nico...

journal_title：Molecular pharmacology

authors： Felici R,Lapucci A,Cavone L,Pratesi S,Berlinguer-Palmini R,Chiarugi A

更新日期：2015-06-01 00:00:00

abstract：:Enzalutamide is a potent second-generation androgen receptor (AR) antagonist with activity in metastatic castrate-resistant prostate cancer (CRPC). Although enzalutamide is initially effective, disease progression inevitably ensues with the emergence of resistance. Intratumoral hypoxia is also associated with CRPC pro...

journal_title：Molecular pharmacology

authors： Fernandez EV,Reece KM,Ley AM,Troutman SM,Sissung TM,Price DK,Chau CH,Figg WD

更新日期：2015-06-01 00:00:00

abstract：:Prenatal exposure to diethylstilbestrol (DES) is known to cause an increased susceptibility to a wide array of clinical disorders in humans. Previous studies from our laboratory demonstrated that prenatal exposure to DES induces thymic atrophy and apoptosis in the thymus. In the current study, we investigated if such ...

journal_title：Molecular pharmacology

authors： Singh NP,Abbas IK,Menard M,Singh UP,Zhang J,Nagarkatti P,Nagarkatti M

更新日期：2015-05-01 00:00:00

abstract：:The orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) is a potent regulator of cholesterol metabolism and bile acid homeostasis. Recently, LRH-1 has been shown to play an important role in intestinal inflammation and in the progression of estrogen receptor positive and negative breast cancers and pancrea...

journal_title：Molecular pharmacology

authors： Corzo CA,Mari Y,Chang MR,Khan T,Kuruvilla D,Nuhant P,Kumar N,West GM,Duckett DR,Roush WR,Griffin PR

更新日期：2015-02-01 00:00:00

abstract：:Secreted R-spondin proteins (RSPOs1-4) function as adult stem cell growth factors by potentiating Wnt signaling. Simultaneous binding of distinct regions of the RSPO Fu1-Fu2 domain module to the extracellular domains (ECDs) of the LGR4 G protein-coupled receptor and the ZNRF3 transmembrane E3 ubiquitin ligase regulate...

journal_title：Molecular pharmacology

authors： Warner ML,Bell T,Pioszak AA

更新日期：2015-01-01 00:00:00

abstract：:Understanding the molecular basis of ligand binding to receptors provides insights useful for rational drug design. This work describes development of a new antagonist radioligand of the type 1 cholecystokinin receptor (CCK1R), (2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-l-H-indole-...

journal_title：Molecular pharmacology

authors： Dong M,Vattelana AM,Lam PC,Orry AJ,Abagyan R,Christopoulos A,Sexton PM,Haines DR,Miller LJ

更新日期：2015-01-01 00:00:00

abstract：:Ryanodine receptors (RyRs) are intracellular membrane channels playing key roles in many Ca(2+) signaling pathways and, as such, are emerging novel therapeutic and insecticidal targets. RyRs are so named because they bind the plant alkaloid ryanodine with high affinity and although it is established that ryanodine pro...

journal_title：Molecular pharmacology

authors： Mukherjee S,Thomas NL,Williams AJ

更新日期：2014-09-01 00:00:00

abstract：:Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin signaling and endosome trafficking, but its precise biologic roles remain incompletely defined. We performed a high-throughput screen of ∼25,000 small molecules to identify inhibitors of DNPEP for use as tools to study its biologic funct...

journal_title：Molecular pharmacology

authors： Chen Y,Tang H,Seibel W,Papoian R,Oh K,Li X,Zhang J,Golczak M,Palczewski K,Kiser PD

更新日期：2014-08-01 00:00:00

abstract：:Both human ether-à-go-go-related gene (hERG1) and the closely related human ether-à-go-go (hEAG1) channel are aberrantly expressed in a large proportion of human cancers. In the present study, we demonstrate that transfection of hERG1 into mouse fibroblasts is sufficient to induce many features characteristic of malig...

journal_title：Molecular pharmacology

authors： Pier DM,Shehatou GS,Giblett S,Pullar CE,Trezise DJ,Pritchard CA,Challiss RA,Mitcheson JS

更新日期：2014-08-01 00:00:00

abstract：:β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on ...

journal_title：Molecular pharmacology

authors： Amanfu RK,Saucerman JJ

更新日期：2014-08-01 00:00:00

abstract：:Previous studies have shown that the transcription factor signal transducer and activator of transcription-3 (STAT3) in podocytes plays an important role in progression of HIV nephropathy and in collapsing forms of glomerulonephritis. Here, we have observed that application of 100 nM angiotensin II (Ang II) to culture...

journal_title：Molecular pharmacology

authors： Abkhezr M,Dryer SE

更新日期：2014-08-01 00:00:00

abstract：:We examined the role of putative trafficking sequences in two GABA(A) receptor subunits: α4 and δ. These subunits assemble with a β subunit to form a subtype of GABA(A) receptor involved in generating the "tonic" outward current. Both α4 and δ subunits contain dibasic retention motifs in homologous positions. When bas...

journal_title：Molecular pharmacology

authors： Bracamontes JR,Li P,Akk G,Steinbach JH

更新日期：2014-07-01 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：:TWIK-related K(+) 1 (TREK1) potassium channels are members of the two-pore domain potassium channel family and contribute to background potassium conductances in many cell types, where their activity can be regulated by a variety of physiologic and pharmacologic mediators. Fenamates such as FFA (flufenamic acid; 2-{[3...

journal_title：Molecular pharmacology

authors： Veale EL,Al-Moubarak E,Bajaria N,Omoto K,Cao L,Tucker SJ,Stevens EB,Mathie A

更新日期：2014-05-01 00:00:00

abstract：:Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to de...

journal_title：Molecular pharmacology

authors： Andersen J,Stuhr-Hansen N,Zachariassen LG,Koldsø H,Schiøtt B,Strømgaard K,Kristensen AS

更新日期：2014-05-01 00:00:00

abstract：:Activators of G protein signaling (AGS), initially discovered in the search for receptor-independent activators of G protein signaling, define a broad panel of biologic regulators that influence signal transfer from receptor to G-protein, guanine nucleotide binding and hydrolysis, G protein subunit interactions, and/o...

journal_title：Molecular pharmacology

authors： Blumer JB,Lanier SM

更新日期：2014-03-01 00:00:00

abstract：:Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity...

journal_title：Molecular pharmacology

authors： Homan KT,Wu E,Wilson MW,Singh P,Larsen SD,Tesmer JJ

更新日期：2014-02-01 00:00:00

abstract：:Voltage-gated sodium channels are inhibited by many local anesthetics, antiarrhythmics, and antiepileptic drugs. The local anesthetic lidocaine appears to be able to access its binding site in the sodium channel only from the membrane phase or from the internal face of the channel. In contrast, the antiepileptic drug ...

journal_title：Molecular pharmacology

authors： Jo S,Bean BP

更新日期：2014-02-01 00:00:00

abstract：:The transient receptor potential cation channel subfamily V member 1 (TRPV1) is known as a thermosensor and integrator of inflammation-induced hyperalgesia. TRPV1 is expressed in a subpopulation of primary afferent neurons that express several different neurotransmitters. The role of the TRPV1 channel in the developme...

journal_title：Molecular pharmacology

authors： Rogoz K,Andersen HH,Kullander K,Lagerström MC

更新日期：2014-02-01 00:00:00

abstract：:Lack of high potency agonists has restricted analysis of the G protein-coupled receptor GPR35. Moreover, marked variation in potency and/or affinity of current ligands between human and rodent orthologs of GPR35 has limited their productive use in rodent models of physiology. Based on the reported modest potency of th...

journal_title：Molecular pharmacology

authors： MacKenzie AE,Caltabiano G,Kent TC,Jenkins L,McCallum JE,Hudson BD,Nicklin SA,Fawcett L,Markwick R,Charlton SJ,Milligan G

更新日期：2014-01-01 00:00:00

abstract：:The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp4...

journal_title：Molecular pharmacology

authors： Merlot AM,Pantarat N,Menezes SV,Sahni S,Richardson DR,Kalinowski DS

更新日期：2013-12-01 00:00:00

abstract：:The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obsc...

journal_title：Molecular pharmacology

authors： Banghart MR,Williams JT,Shah RC,Lavis LD,Sabatini BL

更新日期：2013-11-01 00:00:00

abstract：:The chemokine receptor CCR2 is a G protein-coupled receptor that is activated primarily by the endogenous CC chemokine ligand 2 (CCL2). Many different small-molecule antagonists have been developed to inhibit this receptor, as it is involved in a variety of diseases characterized by chronic inflammation. Unfortunately...

journal_title：Molecular pharmacology

authors： Zweemer AJ,Nederpelt I,Vrieling H,Hafith S,Doornbos ML,de Vries H,Abt J,Gross R,Stamos D,Saunders J,Smit MJ,Ijzerman AP,Heitman LH

更新日期：2013-10-01 00:00:00

abstract：:Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorela...

journal_title：Molecular pharmacology

authors： Neubauer R,Neubauer A,Wölkart G,Schwarzenegger C,Lang B,Schmidt K,Russwurm M,Koesling D,Gorren AC,Schrammel A,Mayer B

更新日期：2013-09-01 00:00:00

abstract：:The mechanism underlying the crosstalk between multiple G protein-coupled receptors remains poorly understood. We previously reported that prostaglandin E receptor EP1 facilitates dopamine D1 receptor signaling in striatal slices and promotes behavioral responses induced by D1 receptor agonists. Here, using human embr...

journal_title：Molecular pharmacology

authors： Ehrlich AT,Furuyashiki T,Kitaoka S,Kakizuka A,Narumiya S

更新日期：2013-09-01 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：:Retinoid X receptor α [RXRα; nuclear receptor (NR)2B1] is a crucial regulator in the expression of a broad array of hepatic genes under both normal and pathologic conditions. During inflammation, RXRα undergoes rapid post-translational modifications, including c-Jun N-terminal kinase (JNK)-mediated phosphorylation, wh...

journal_title：Molecular pharmacology

authors： Schneider Aguirre R,Karpen SJ

更新日期：2013-08-01 00:00:00

abstract：:The use of classic antipsychotic drugs is limited by the occurrence of extrapyramidal motor symptoms, which are caused by dopamine (DA) receptor blockade in the neostriatum. We examined the impact of early-life stress on haloperidol-induced catalepsy using the rat model of prenatal restraint stress (PRS). Adult "PRS r...

journal_title：Molecular pharmacology

authors： Marrocco J,Mairesse J,Bucci D,Lionetto L,Battaglia G,Consolazione M,Ravasi L,Simmaco M,Morley-Fletcher S,Maccari S,Nicoletti F

更新日期：2013-08-01 00:00:00

abstract：:Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the boron-dipyrromethene [Bodipy (558/568)] fluorophore via spacer...

journal_title：Molecular pharmacology

authors： Daval SB,Kellenberger E,Bonnet D,Utard V,Galzi JL,Ilien B

更新日期：2013-07-01 00:00:00

abstract：:Organic anion transporter-1 (OAT1) mediates the body disposition of a diverse array of clinically important drugs, including anti-HIV therapeutics, antitumor drugs, antibiotics, antihypertensives, and anti-inflammatories. Therefore, understanding the regulation of OAT1 has profound clinical significance. We previously...

journal_title：Molecular pharmacology

authors： Li S,Zhang Q,You G

更新日期：2013-07-01 00:00:00

abstract：:A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant γ-aminobutyric acid type A (GABAA) receptor with unique chara...

journal_title：Molecular pharmacology

authors： Stewart DS,Hotta M,Desai R,Forman SA

更新日期：2013-06-01 00:00:00

abstract：:We previously described the development of genetic models to study the in vivo functions of the hepatic cytochrome P450 (P450) system, through the hepatic deletion of either cytochrome P450 oxidoreductase [POR; HRN (hepatic reductase null) line] or cytochrome b(5) [HBN (hepatic cytochrome b(5) null) line]. However, HR...

journal_title：Molecular pharmacology

authors： Henderson CJ,McLaughlin LA,Wolf CR

更新日期：2013-06-01 00:00:00

abstract：:The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1. As the Janus tyrosine kinase 2 (Jak2)/signal trans...

journal_title：Molecular pharmacology

authors： Lopez-Haber C,Kazanietz MG

更新日期：2013-05-01 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

authors： Noetzel MJ,Gregory KJ,Vinson PN,Manka JT,Stauffer SR,Lindsley CW,Niswender CM,Xiang Z,Conn PJ

更新日期：2013-04-01 00:00:00

abstract：:The Integrated Stress Response (ISR) is a signaling program that enables cellular adaptation to stressful conditions like hypoxia and nutrient deprivation in the tumor microenvironment. An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in...

journal_title：Molecular pharmacology

authors： Sayers CM,Papandreou I,Guttmann DM,Maas NL,Diehl JA,Witze ES,Koong AC,Koumenis C

更新日期：2013-03-01 00:00:00

abstract：:We have previously identified allosteric modulators of the cannabinoid CB(1) receptor (Org 27569, PSNCBAM-1) that display a contradictory pharmacological profile: increasing the specific binding of the CB(1) receptor agonist [(3)H]CP55940 but producing a decrease in CB(1) receptor agonist efficacy. Here we investigate...

journal_title：Molecular pharmacology

authors： Baillie GL,Horswill JG,Anavi-Goffer S,Reggio PH,Bolognini D,Abood ME,McAllister S,Strange PG,Stephens GJ,Pertwee RG,Ross RA

更新日期：2013-02-01 00:00:00

abstract：:This study assessed how conformational information encoded by ligand binding to δ-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reci...

journal_title：Molecular pharmacology

authors： Richard-Lalonde M,Nagi K,Audet N,Sleno R,Amraei M,Hogue M,Balboni G,Schiller PW,Bouvier M,Hébert TE,Pineyro G

更新日期：2013-02-01 00:00:00

abstract：:Exchange protein directly activated by cAMP (EPAC) and cAMP-dependent protein kinase (PKA) are two intracellular receptors that mediate the effects of the prototypic second messenger cAMP. Identifying pharmacological probes for selectively modulating EPAC activity represents a significant unmet need within the researc...

journal_title：Molecular pharmacology

authors： Almahariq M,Tsalkova T,Mei FC,Chen H,Zhou J,Sastry SK,Schwede F,Cheng X

更新日期：2013-01-01 00:00:00