Discovery of a Tamoxifen-related compound that suppresses glial l-glutamate transport activity without interaction with estrogen receptors.

Abstract:

:We recently found that tamoxifen suppresses l-glutamate transport activity of cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter-inhibitory activity from the estrogen receptor-mediated genomic effects, we synthesized several compounds structurally related to tamoxifen. Among them, we identified two compounds, 1 (YAK01) and 3 (YAK037), which potently inhibited l-glutamate transporter activity. The inhibitory effect of 1 was found to be mediated through estrogen receptors and the mitogen-activated protein kinase (MAPK)/phosphatidylinositol 3-kinase (PI3K) pathway, though 1 showed greatly reduced transactivation activity compared with that of 17β-estradiol. On the other hand, compound 3 exerted its inhibitory effect through an estrogen receptor-independent and MAPK-independent, but PI3K-dependent pathway, and showed no transactivation activity. Compound 3 may represent a new platform for developing novel l-glutamate transporter inhibitors with higher brain transfer rates and reduced adverse effects.

journal_name

ACS Chem Neurosci

authors

Sato K,Kuriwaki J,Takahashi K,Saito Y,Oka J,Otani Y,Sha Y,Nakazawa K,Sekino Y,Ohwada T

doi

10.1021/cn200091w

subject

Has Abstract

pub_date

2012-02-15 00:00:00

pages

105-13

issue

2

issn

1948-7193

journal_volume

3

pub_type

杂志文章
  • Noradrenergic Modulation of Dopamine Transmission Evoked by Electrical Stimulation of the Locus Coeruleus in the Rat Brain.

    abstract::Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlyi...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00078

    authors: Park JW,Bhimani RV,Park J

    更新日期:2017-09-20 00:00:00

  • Conformational Propensities of Peptides Mimicking Transmembrane Helix 5 and Motif C in Wild-type and Mutant Vesicular Acetylcholine Transporters.

    abstract::Vesicular acetylcholine transporter (VAChT) is a member of the major facilitator superfamily (MFS). It contains conserved sequence motifs originally defined in the bacterial multidrug resistance transporter family of the MFS. Motif C (GSLV(227) A(228)PPFGGIL) is located at the C-terminal end of transmembrane helix 5 (...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn900033s

    authors: Luo J,Parsons SM

    更新日期:2010-05-19 00:00:00

  • Imaging Fast-Acting Drug Effects in Humans Using 1H-MRS.

    abstract::Proton magnetic spectroscopy (1H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmac...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00474

    authors: White TL,Gonsalves MA

    更新日期:2020-09-02 00:00:00

  • Mimicking biological design and computing principles in artificial olfaction.

    abstract::Biology has inspired solutions to many engineering problems, including chemical sensing. Modern approaches to chemical sensing have been based on the biological principle of combining cross-selective chemical sensors with a pattern recognition engine to identify odors. Here, we review some recent advances made in mimi...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn200027r

    authors: Raman B,Stopfer M,Semancik S

    更新日期:2011-05-27 00:00:00

  • Pharmacological Characterizations of anti-Dementia Memantine Nitrate via Neuroprotection and Vasodilation in Vitro and in Vivo.

    abstract::We have previously designed and synthesized a series of novel memantine nitrates, and some of them have shown neuroprotective effects; however, the detailed mechanisms remain unknown. In this study, we demonstrated that MN-12, one of the memantine nitrates, concentration-dependently protected against glutamate-induced...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00242

    authors: Mak S,Liu Z,Wu L,Guo B,Luo F,Liu Z,Hu S,Wang J,Cui G,Sun Y,Wang Y,Zhang G,Han Y,Zhang Z

    更新日期:2020-02-05 00:00:00

  • Positive Allosteric Modulation of the 5-HT1A Receptor by Indole-Based Synthetic Cannabinoids Abused by Humans.

    abstract::The nonmedical (i.e., recreational) misuse of synthetic cannabinoids (SCs) is a worldwide public health problem. When compared to cannabis, the misuse of SCs is associated with a higher incidence of serious adverse effects, suggesting the possible involvement of noncannabinoid sites of action. Here, we find that, unli...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00034

    authors: Yano H,Adhikari P,Naing S,Hoffman AF,Baumann MH,Lupica CR,Shi L

    更新日期:2020-05-20 00:00:00

  • ACS chemical neuroscience molecule spotlight on savella.

    abstract::Savella (milnacipran), a selective serotonin and noradrenaline reuptake inhibitor, was approved by the FDA on January 14th, 2009, for the treatment of fibromyalgia. ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn1000233

    authors: Hopkins CR

    更新日期:2010-05-19 00:00:00

  • (-)-Hardwickiic Acid and Hautriwaic Acid Induce Antinociception via Blockade of Tetrodotoxin-Sensitive Voltage-Dependent Sodium Channels.

    abstract::For an affliction that debilitates an estimated 50 million adults in the United States, the current chronic pain management approaches are inadequate. The Centers for Disease Control and Prevention have called for a minimization in opioid prescription and use for chronic pain conditions, and thus, it is imperative to ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00617

    authors: Cai S,Bellampalli SS,Yu J,Li W,Ji Y,Wijeratne EMK,Dorame A,Luo S,Shan Z,Khanna M,Moutal A,Streicher JM,Gunatilaka AAL,Khanna R

    更新日期:2019-03-20 00:00:00

  • Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

    abstract::Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding th...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn500049n

    authors: Angelovski G,Gottschalk S,Milošević M,Engelmann J,Hagberg GE,Kadjane P,Andjus P,Logothetis NK

    更新日期:2014-05-21 00:00:00

  • Detection of orexin A neuropeptide in biological fluids using a zinc oxide field effect transistor.

    abstract::Biomarkers which are indicative of acute physiological and emotional states are studied in a number of different areas in cognitive neuroscience. Currently, many cognitive studies are conducted based on programmed tasks followed by timed biofluid sampling, central laboratory processing, and followed by data analysis. ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300159e

    authors: Hagen J,Lyon W,Chushak Y,Tomczak M,Naik R,Stone M,Kelley-Loughnane N

    更新日期:2013-03-20 00:00:00

  • Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction.

    abstract::Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote coca...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300072u

    authors: Cunningham KA,Anastasio NC,Fox RG,Stutz SJ,Bubar MJ,Swinford SE,Watson CS,Gilbertson SR,Rice KC,Rosenzweig-Lipson S,Moeller FG

    更新日期:2013-01-16 00:00:00

  • Discovery and Optimization of Triazine Nitrile Inhibitors of Toxoplasma gondii Cathepsin L for the Potential Treatment of Chronic Toxoplasmosis in the CNS.

    abstract::With roughly 2 billion people infected, the neurotropic protozoan Toxoplasma gondii remains one of the most pervasive and infectious parasites. Toxoplasma infection is the second leading cause of death due to foodborne illness in the United States, causes severe disease in immunocompromised patients, and is correlated...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00674

    authors: Zwicker JD,Smith D,Guerra AJ,Hitchens JR,Haug N,Vander Roest S,Lee P,Wen B,Sun D,Wang L,Keep RF,Xiang J,Carruthers VB,Larsen SD

    更新日期:2020-08-19 00:00:00

  • Novel Disassembly Mechanisms of Sigmoid Aβ42 Protofibrils by Introduced Neutral and Charged Drug Molecules.

    abstract::Alzheimer's disease (AD) is characterized by fibrillar deposits of amyloid-β (Aβ) peptides and neurofibrillary tangles of Tau proteins. Aβ peptides are composed of 37-49 residues, among which the Aβ42 isoform is particularly toxic and aggregation-prone and is enriched in the plaques of AD brains and thus considered ce...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00550

    authors: Xing X,Liu C,Ali A,Kang B,Li P,Ai H

    更新日期:2020-01-02 00:00:00

  • AMPA Receptor Noncompetitive Inhibitors Occupy a Promiscuous Binding Site.

    abstract::Noncompetitive inhibitors of AMPA receptors have attracted interest in recent years as antiepileptic drugs. However, their development is hindered by a lack of detailed understanding of the protein-inhibitor interaction mechanisms. Recently, structures of AMPA receptor complexes with the structurally dissimilar, nonco...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00344

    authors: Narangoda C,Sakipov SN,Kurnikova MG

    更新日期:2019-11-20 00:00:00

  • Akt-dependent and isoform-specific regulation of dopamine transporter cell surface expression.

    abstract::Dopamine (DA) is a neurotransmitter implicated in multiple functions, including movement, cognition, motivation, and reward. The DA transporter (DAT) is responsible for clearing extracellular DA, thereby terminating DA neurotransmission. Previously, it has been shown that insulin signaling through protein kinase B/Akt...

    journal_title:ACS chemical neuroscience

    pub_type: 信件

    doi:10.1021/cn100031t

    authors: Speed NK,Matthies HJ,Kennedy JP,Vaughan RA,Javitch JA,Russo SJ,Lindsley CW,Niswender K,Galli A

    更新日期:2010-07-21 00:00:00

  • Evidence for an extracellular zinc-veneer in rodent brains from experiments with Zn-ionophores and ZnT3 knockouts.

    abstract::Ionic zinc is found at a high concentration in some glutamatergic vesicles of the mammalian brain. Ionic zinc is also found chelated to macromolecules in the extracellular space, constituting what has been called the "zinc veneer". In this communication we show that the zinc ionophore, pyrithione, can be used to demon...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300061z

    authors: Nydegger I,Rumschik SM,Zhao J,Kay AR

    更新日期:2012-10-17 00:00:00

  • (3-Cyano-5-fluorophenyl)biaryl negative allosteric modulators of mGlu(5): Discovery of a new tool compound with activity in the OSS mouse model of addiction.

    abstract::Glutamate is the major excitatory transmitter in the mammalian CNS, exerting its effects through both ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGlus) belong to family C of the G-protein-coupled receptors (GPCRs). The eight mGlus identified to date are classified into three...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn100099n

    authors: Lindsley CW,Bates BS,Menon UN,Jadhav SB,Kane AS,Jones CK,Rodriguez AL,Conn PJ,Olsen CM,Winder DG,Emmitte KA

    更新日期:2011-08-17 00:00:00

  • Rethinking Glioblastoma Therapy: MDA-9/Syntenin Targeted Small Molecule.

    abstract::Effective therapies for glioblastoma multiforme (GBM) are not currently available. A small molecule has been identified using fragment-based drug-discovery guided by NMR that targets important protein-protein interactions controlling GBM invasion and pathogenicity. This first generation drug displays excellent pharmac...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.9b00016

    authors: Das SK,Sarkar D,Cavenee WK,Emdad L,Fisher PB

    更新日期:2019-03-20 00:00:00

  • Tautomerization Effect of Histidines on Oligomer Aggregation of β-Amyloid(1-40/42) during the Early Stage: Tautomerism Hypothesis for Misfolding Protein Aggregation.

    abstract::As the intrinsic origin of the hypothesis for β-amyloid (Aβ) from Alzheimer's disease, histidine behaviors were found to play a crucial role in Aβ aggregation. To investigate the histidine behaviors during the early stage of aggregation, Aβ40/42 pentamers with different histidine isomer states were simulated at the at...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00094

    authors: Xing X,Zhao W,Hu D,Kang B,Shi H,Lee JY,Ai H

    更新日期:2019-05-15 00:00:00

  • Diverse Effects of Gut-Derived Serotonin in Intestinal Inflammation.

    abstract::The gut is the largest producer of serotonin or 5-hydroxytryptamine (5-HT) in the human body, and 5-HT has been recognized as an important signaling molecule in the gut for decades. There are two distinct sources of enteric 5-HT. Mucosal 5-HT is predominantly produced by enterochromaffin (EC) cells of the gastrointest...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.6b00414

    authors: Shajib MS,Baranov A,Khan WI

    更新日期:2017-05-17 00:00:00

  • Oleocanthal-Rich Extra-Virgin Olive Oil Restores the Blood-Brain Barrier Function through NLRP3 Inflammasome Inhibition Simultaneously with Autophagy Induction in TgSwDI Mice.

    abstract::Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by multiple hallmarks including extracellular amyloid (Aβ) plaques, neurofibrillary tangles, dysfunctional blood-brain barrier (BBB), neuroinflammation, and impaired autophagy. Thus, novel strategies that target multiple disease pathways wo...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00175

    authors: Al Rihani SB,Darakjian LI,Kaddoumi A

    更新日期:2019-08-21 00:00:00

  • Microglia-Based Phenotypic Screening Identifies a Novel Inhibitor of Neuroinflammation Effective in Alzheimer's Disease Models.

    abstract::Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic sc...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00125

    authors: Zhou W,Zhong G,Fu S,Xie H,Chi T,Li L,Rao X,Zeng S,Xu D,Wang H,Sheng G,Ji X,Liu X,Ji X,Wu D,Zou L,Tortorella M,Zhang K,Hu W

    更新日期:2016-11-16 00:00:00

  • Probing the neurochemical correlates of motivation and decision making.

    abstract::Online electrochemical detection techniques are the state-of-the-art for evaluating chemical communication in the brain underlying motivated behavior and decision making. In this Viewpoint, we discuss avenues for future technological development, as well as the requirement for increasingly sophisticated and interdisci...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn500322y

    authors: Wassum KM,Phillips PE

    更新日期:2015-01-21 00:00:00

  • Ethylatropine Bromide as a Peripherally Restricted Muscarinic Antagonist.

    abstract::Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent o...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00334

    authors: Rojas A,Ganesh T,Walker A,Dingledine R

    更新日期:2017-04-19 00:00:00

  • Discovery of Melanocortin Ligands via a Double Simultaneous Substitution Strategy Based on the Ac-His-dPhe-Arg-Trp-NH2 Template.

    abstract::The melanocortin system regulates an array of diverse physiological functions including pigmentation, feeding behavior, energy homeostasis, cardiovascular regulation, sexual function, and steroidogenesis. Endogenous melanocortin agonist ligands all possess the minimal messaging tetrapeptide sequence His-Phe-Arg-Trp. B...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00181

    authors: Todorovic A,Lensing CJ,Holder JR,Scott JW,Sorensen NB,Haskell-Luevano C

    更新日期:2018-11-21 00:00:00

  • Effects of Zn2+ binding on the structural and dynamic properties of amyloid β peptide associated with Alzheimer's disease: Asp1 or Glu11?

    abstract::Extensive experimental and computational studies have suggested that multiple Zn(2+) binding modes in amyloid β (Aβ) peptides could exist simultaneously. However, consistent results have not been obtained for the effects of Zn(2+) binding on Aβ structure, dynamics, and kinetics in particular. Some key questions such a...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn4001445

    authors: Xu L,Wang X,Wang X

    更新日期:2013-11-20 00:00:00

  • Phospho-Tau Impairs Nuclear-Cytoplasmic Transport.

    abstract::Aggregation of hyperphosphorylated tau is the hallmark of several tauopathies, including Alzheimer's disease (AD). Although the mechanism underlying tau-associated neuronal damage remains unclear, it is believed that tau hyperphosphorylation is one of the key features in disease progression. A recent study demonstrate...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.8b00632

    authors: Tripathi T,Prakash J,Shav-Tal Y

    更新日期:2019-01-16 00:00:00

  • Alzheimer's Amyloid-β Sequesters Caspase-3 in Vitro via Its C-Terminal Tail.

    abstract::Amyloid-β (Aβ), the main constituent in senile plaques found in the brain of patients with Alzheimer's disease (AD), is considered as a causative factor in AD pathogenesis. The clinical examination of the brains of patients with AD has demonstrated that caspase-3 colocalizes with senile plaques. Cellular studies have ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00049

    authors: Chang YJ,Linh NH,Shih YH,Yu HM,Li MS,Chen YR

    更新日期:2016-08-17 00:00:00

  • The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease.

    abstract::The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer'...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00014

    authors: R Cardoso B,Hare DJ,Lind M,McLean CA,Volitakis I,Laws SM,Masters CL,Bush AI,Roberts BR

    更新日期:2017-07-19 00:00:00

  • A small linear peptide encompassing the NGF N-terminus partly mimics the biological activities of the entire neurotrophin in PC12 cells.

    abstract::Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory ganglia, nerve growth factor (NGF) became the prototype of the large family of neurotrophins. The use of primary cultures and clonal cell lines has revealed several distinct actions of NGF and other neurotrophins. Among severa...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00069

    authors: Travaglia A,Pietropaolo A,Di Martino R,Nicoletti VG,La Mendola D,Calissano P,Rizzarelli E

    更新日期:2015-08-19 00:00:00