• abstract = 'The central nervous system glutamate receptors are an important target for drug discovery. (ku.dk)
  • Dual Piperidine-Based Histamine H and Sigma-1 Receptor Ligands in the Treatment of Nociceptive and Neuropathic Pain. (iasp-pain.org)
  • In search of new dual-acting histamine H/sigma-1 receptor ligands, we designed a series of compounds structurally based on highly active ligands previously studied and described by our team. (iasp-pain.org)
  • Sigma-1 receptor (Sig1R) is a ligand-regulated protein which, since its discovery, has been widely studied as a novel target to treat neurological disorders, including seizures. (rsu.lv)
  • The glucagon-like peptide-1 receptor (GLP-1R) is an important regulator of blood glucose homeostasis. (cam.ac.uk)
  • is the name of the ligand. (lu.se)
  • The mechanism by which the androgen receptor (AR) distinguishes between agonist and antagonist ligands is poorly understood. (rcsb.org)
  • KDN21 is a bivalent ligand that contains δ and κ opioid antagonist pharmacophores linked through a 21-atom spacer. (aspetjournals.org)
  • KDN21 contains δ and κ opioid receptor antagonist pharmacophores that are connected through a 21-atom spacer ( Fig. 1 ). (aspetjournals.org)
  • ancestral variant) in the ligand-binding domain of the aryl hydrocarbon receptor (AHR) gene. (oregonstate.edu)
  • Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon receptor (AhR) ligands that induce AhR-dependent Tregs and prevent murine graft-versus-host disease. (oregonstate.edu)
  • The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays multiple roles in regulation of immune and inflammatory responses. (oregonstate.edu)
  • We studied binding of ligands from different wines to the peroxisome proliferator-activated receptor γ (PPARγ), a key factor in glucose and lipid metabolism. (rsc.org)
  • In contrast, the human AHR retains the ancestral sensitivity observed in primates to non-toxic endogenous AHR ligands (e.g. indole, indoxyl sulfate). (oregonstate.edu)
  • The actions of the endogenous ORL 1 -receptor ligand nociceptin on the membrane properties and synaptic currents in rat periaqueductal gray (PAG) neurons were examined by the use of whole-cell patch-clamp recording in brain slices. (jneurosci.org)
  • Endocannabinoid: endogenous cannabinoid receptor ligands with neuromodulatory action. (bvsalud.org)
  • Follicle-stimulating hormone receptor (FSHR) is a G protein-coupled receptor (GPCR) with pivotal roles in reproduction. (frontiersin.org)
  • In turn, receptor signaling is known to drive or regulate GPCR trafficking. (frontiersin.org)
  • Here, we report that the recently sequenced genome from the red flour beetle Tribolium castaneum contains a gene coding for an oxytocin/vasopressin-like peptide, identical to the locust peptide, which we named inotocin (for insect oxytocin/vasopressin-like peptide) and a gene coding for an inotocin G protein-coupled receptor (GPCR). (lu.se)
  • This GPCR is strongly activated by low concentrations of inotocin (EC 50 , 5 × 10 -9 M), demonstrating that it is the inotocin receptor. (lu.se)
  • JAK2 is a member of the class I type tyrosine kinase family of enzymes and is involved in signal transduction for erythropoietin , thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors among other entities. (msdmanuals.com)
  • Lysosomal inhibitors prolong the half-life of both receptor and ligand. (portlandpress.com)
  • Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers, rather than beta-adrenergic blockers, should be considered as first-line therapy for hypertension in patients with type 2 diabetes mellitus who are obese. (medscape.com)
  • These receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins. (reactome.org)
  • We assessed the efficacy and potency of structurally distinct KOR small molecule and peptide ligands. (ku.edu)
  • In this work we synthesized 18 biphenylic carboxamides as new CB2-selective ligands and evaluated their pharmacological profiles. (nih.gov)
  • Scholars@Duke publication: Multidimensional de novo design reveals 5-HT2B receptor-selective ligands. (duke.edu)
  • The present study used in vitro expression systems to investigate interactions of members of the KDN series with δ-κ heterodimers through competition binding using selective ligands and the mitogen-activated protein kinase (MAPK) assay. (aspetjournals.org)
  • On the other hand, due to the scarcity of sigma2 selective ligands, less is understood about this subtype. (umsystem.edu)
  • Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. (rcsb.org)
  • Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. (rcsb.org)
  • Recently, our laboratory discovered selective androgen receptor modulators, which structurally resemble the nonsteroidal AR antagonists bicalutamide and hydroxyflutamide but act as agonists for the androgen receptor in a tissue-selective manner. (rcsb.org)
  • To study the structural basis of pathological remodelling and altered calcium channel functional states in the heart, we sought to re-purpose high-affinity ligands of the cardiac calcium channel, the ryanodine receptor (RyR2), into super-resolution imaging probes. (whiterose.ac.uk)
  • This research project is focused on the preparation of a Tc-99m labeled complex designed to retain high affinity to the sigma1 receptor subtype. (umsystem.edu)
  • Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors. (lu.se)
  • Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand-efficient 5-HT2B modulators with sustained cell-based effects. (duke.edu)
  • Given the critical nature of receptor internalization and endosomal signaling for FSHR activity, we assessed whether these compounds exhibit differential abilities to alter receptor endosomal trafficking and signaling within the VEE. (frontiersin.org)
  • All compounds exhibited a similar requirement for receptor internalization to increase cAMP and proportion of FSHR endosomes with active Gαs, suggesting regulation of cAMP signaling induced by T1 may be altered. (frontiersin.org)
  • The growth hormone (GH) receptor (GHR) is a mammalian plasma membrane protein whose internalization is mediated by the ubiquitin-proteasome pathway. (portlandpress.com)
  • In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less β -arrestin recruitment and receptor internalization. (aspetjournals.org)
  • therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptional signaling. (ku.dk)
  • These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling, suggesting that ligand-mediated endocytosis is not a prerequisite for GH-induced gene transcription. (ku.dk)
  • Bond probabilities between each ligand investigated and Qi receptor residues in the ranges F10 to I44 and I190 to F235. (figshare.com)
  • A subfamily of ligand-gated ion channel receptors that share a characteristic loop which is formed by a disulfide bond between two CYSTEINE residues. (bvsalud.org)
  • Intermediate levels of generalization were observed with the subtype nonselective sigma ligands 3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP] (69.0%) and 1,3-di(2-tolyl)guanidine (DTG) (73.5%) but not with the sigma1-selective agents (+)-N-allylnormetazocine [(+)-SKF 10,047] and (+)-pentazocine. (erowid.org)
  • Such probes may be useful to investigate the biological role of CB2 receptors in cellular assays. (nih.gov)
  • Thus, standard commercially-available assays cannot be applied to test for agonistic or antagonistic properties of AT(2)R ligands. (mdc-berlin.de)
  • This lack of standard assays has hampered the development of new drugs targeting the AT(2)R. Therefore, we aimed at developing a reliable, technically easy assay for the determination of intrinsic activity of AT(2)R ligands, primarily for distinguishing between AT(2)R agonists and antagonists. (mdc-berlin.de)
  • 5'OH dsRNA has been shown to activate RIG-I, indicating an overlap in ligands between LGP2 and RIG-I. Competition assays show 5'OH dsRNA preferentially interacts with LGP2, suggesting a mechanism in which LGP2 sequesters non-PAMP ligand of RIG-I to diminish misactivations. (rutgers.edu)
  • Divergent Ah receptor ligand selectivity during hominin evolution. (oregonstate.edu)
  • Regarding the selectivity of KDN21 for phenotypic δ and κ opioid receptors, we investigated the effect of KDN21 on the activation of MAPKs [extracellular signal-regulated kinases 1 and 2 (ERK1/2)] by δ- or κ-selective agonists. (aspetjournals.org)
  • These findings, along with observations that ibogaine has appreciable affinity for sigma2 receptors, suggest that these receptors may be involved in the ibogaine discriminative stimulus. (erowid.org)
  • The latter observations taken together with the finding that both nalorphine (>100 microM) and diprenorphine (30 microM) have extremely low affinity for sigma2 receptors, suggest that the ibogaine-appropriate responding produced by these agents is not mediated by sigma2 receptors. (erowid.org)
  • However, we kept in mind that within the previous series, a pair of closely related compounds, and , differing only in the piperazine/piperidine moiety in the structural core showed a significantly different affinity at sigma-1 receptors (σRs). (iasp-pain.org)
  • When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. (aspetjournals.org)
  • We have shown previously that when using [ 3 H]diprenorphine as radioligand, KDN21 displayed greatly enhanced affinity in this series for coexpressed δ and κ opioid receptors (CDK). (aspetjournals.org)
  • In this regard, the use of the selective radioligands [ 3 H]naltrindole and [ 3 H]norbinaltorphimine (nor-BNI) in competition binding studies revealed that KDN21 has much higher affinity than other KDN members for CDK and bound to CDK more selectively relative to mixed δ and κ opioid receptors or singly expressed δ and κ opioid receptors. (aspetjournals.org)
  • Morphine pharmacology in β -arrestin-2 knockout mice suggested that a ligand that promotes coupling of the μ -opioid receptor (MOR) to G proteins, but not β -arrestins, would result in higher analgesic efficacy, less gastrointestinal dysfunction, and less respiratory suppression than morphine. (aspetjournals.org)
  • TRV130 successfully translates evidence that analgesic and adverse MOR signaling pathways are distinct into a biased ligand with differentiated pharmacology. (aspetjournals.org)
  • Since the discovery of the two main cannabinoid receptors CB1 and CB2 in the early '90, intensive research reviled a substantial influence of this system on many physiological and pathophysiological processes. (logos-verlag.de)
  • The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2′-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate G i/o -coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. (ku.dk)
  • With the discovery of the protective arm of the renin-angiotensin system (RAS), interest has grown in protective RAS-related receptors such as the angiotensin AT(2)-receptor [AT(2)R] as potential new drug targets. (mdc-berlin.de)
  • Membrane trafficking of G protein-coupled receptors (GPCRs) tightly orchestrates the signaling from this superfamily of signaling receptors. (frontiersin.org)
  • We screened a ChemBridge small molecule library and identified 10-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ) as a potent AhR ligand that was rapidly metabolized and not cytotoxic to proliferating T cells. (oregonstate.edu)
  • We explored the utility of the real-time FLIPR Membrane Potential (FMP) assay as a method to assess kappa opioid receptor (KOR)-induced hyperpolarization. (ku.edu)
  • Ligand-specific differences in membrane trafficking of the GLP-1R influence its signalling properties and therapeutic potential in type 2 diabetes. (cam.ac.uk)
  • The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. (medlineplus.gov)
  • Normal neuromuscular junction showing a presynaptic terminal with a motor nerve ending in an enlargement (bouton terminale): Synaptic cleft and postsynaptic membrane with multiple folds and embedded with several acetylcholine receptors. (medscape.com)
  • In a combinatorial synthetic approach, several new libraries of new ligands were synthesised and subsequently pharmacological tested. (logos-verlag.de)
  • An important step toward this goal would be the development of pharmacological tools that selectively target opioid receptor heterodimers. (aspetjournals.org)
  • The phenylpiperazine and phenylpiperidine chemical classes of ligands have been identified to bind at sigma1 receptor sites and a pharmacological model has been proposed. (umsystem.edu)
  • We performed in silico molecular docking and dynamic studies and demonstrated that type and size of substitution at the C17 position of the cortisol backbone confer a unique stable conformation to GR on ligand binding that is critical for inhibitory activity. (oregonstate.edu)
  • In an attempt to determine which of these receptor interactions are involved in the in vivo effects of ibogaine, ligands for sigma, PCP, and opiate receptors were assessed for their ability to substitute for or to antagonize the ibogaine-induced discriminative stimulus (10 mg/kg I.P., 60 min presession) in Fischer-344 rats. (erowid.org)
  • Other experiments revealed that the binding of naltrindole to δ opioid receptors could increase the binding of nor-BNI to κ opioid receptors and vice versa, suggesting reciprocal allosteric modulation of receptors in the heterodimer. (aspetjournals.org)
  • Although cellular and in vivo studies have provided considerable insight into the downstream consequences of Notch signalling, relatively little is known about the molecular basis of the receptor/ligand interaction and initial stages of activation. (nih.gov)
  • Alternate glucocorticoid receptor ligand binding structures influence outcomes in an in vivo tissue regeneration model. (oregonstate.edu)
  • In vivo assessment of these corticosteroid analogs is essential to understand the difference in molecular signaling of the ligands that share the corticosteroid backbone. (oregonstate.edu)
  • The results of studies with selective agonists and antagonists in vivo are consistent with cooperativity between δ and κ receptors, and it has been proposed that the putative δ 1 and κ 2 opioid receptor subtypes are actually phenotypes ( Portoghese and Lunzer, 2003 ). (aspetjournals.org)
  • Although the in vitro binding data were consistent with the in vivo study, it did not identify the binding characteristics of each of the bridged receptors. (aspetjournals.org)
  • Non-invasive imaging of the sigma receptor in vivo would lead to a better understanding of the role that sigma receptors play in health and disease. (umsystem.edu)
  • The ameliorating effects of red wine on metabolic diseases may be partially explained by the presence of PPARγ ligands . (rsc.org)
  • Click on one of the subfamilies of IgSF or TNFRSF co-signaling receptors shown in the Explore Pathways box below to see how the different members of each family affect T cell activation. (rndsystems.com)
  • Although the mechanism of action of ibogaine, a hallucinogen that may be useful in the treatment of addiction, remains unknown, receptor binding studies suggest that ibogaine produces its effects via interactions with multiple receptor types. (erowid.org)
  • In contrast to sigma2 and opiate receptors, ibogaine's reported interactions with NMDA receptors do not appear to be involved in its discriminative stimulus, as neither PCP nor MK-801 produced a significant level of ibogaine-appropriate responding. (erowid.org)
  • A network data frame (tibble) with ligand-receptor interactions suitable for use with NicheNet. (omnipathdb.org)
  • As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages promotes the production of chemokines and proinflammatory cytokines to maintain the immunosuppressive tumor environment of extramammary Paget's disease (EMPD). (iiarjournals.org)
  • For example, Paget's cells release soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) into the tumor microenvironment, stimulating RANK + TAMs to produce CCL17, which recruits Tregs into the lesional skin of patients with extramammary Paget's disease (EMPD) ( 11 , 17 ). (iiarjournals.org)
  • Description: The receptor activator of NF-kappaB ligand (RANK-L) is a recently discovered member of the TNF-ligand family involved in the regulation of the T cell-dependent immune response, lymph node organogenesis and bone formation. (glucagon-receptor.com)
  • A converse goal of receptor-ligand kinetics is to estimate the rate constants and/or dissociation constants of the receptors and ligands from experimental kinetic or equilibrium data. (wikipedia.org)
  • ligands, based on the measured ligand binding dissociation constant (Kd). (duke.edu)
  • To our knowledge, this is the first report on the molecular cloning of an oxytocin/vasopressin-like receptor and its ligand from arthropods. (lu.se)
  • G-protein-coupled receptors (GPCRs) are typically considered to function as monomers. (aspetjournals.org)
  • Opioid receptors belong to rhodopsin receptor family of GPCRs. (aspetjournals.org)
  • Thus, the present study offers evidence that unlike NMDA receptors, both sigma2 and opiate receptors may be involved in the ibogaine discriminative stimulus. (erowid.org)
  • The estrogen receptor (ER) is a transcription factor whose activity is normally activated by the hormone estradiol and inhibited by antiestrogen. (eurekamag.com)
  • Therapeutic Ligands Antagonize Estrogen Receptor Function by Impairing Its Mobility. (bvsalud.org)
  • Estrogen receptor -positive (ER+) breast cancers frequently remain dependent on ER signaling even after acquiring resistance to endocrine agents, prompting the development of optimized ER antagonists. (bvsalud.org)
  • This positioning allows the receptor to attach (bind) to other proteins, called ligands, outside the cell and to receive signals that help the cell respond to its environment. (medlineplus.gov)
  • Sequence alignments indicated conservation of the ephrin-B2 and ephrin-B3 receptor binding sites, the glycosylation site on the G attachment protein, as well as the editing site in phosphoprotein, suggesting production of nonstructural proteins V and W, known to counteract the host innate immunity. (cdc.gov)
  • Immunohistochemical staining of MMP1 and MMP25 as well as chemokine (C-C motif) ligand (CCL) 5 in the lesional skin from five patients with PCAC showed a substantial number of MMP1-bearing cells and MMP25-bearing cells, as well as CCL5-producing cells, that were distributed in the lesional skin. (iiarjournals.org)
  • Such drugs are devoid of the undesired central side effects that are typically mediated by the CB1 receptor. (nih.gov)
  • These receptors typically contain five subunits with the cysteine-loop occurring near an N-terminal extracellular domain. (bvsalud.org)
  • But what makes the sigma receptors so great is the fact that they bind a variety of ligands. (umsystem.edu)
  • To investigate why subtle structural changes to both the ligand and the receptor (i.e. mutations) result in drastic changes in activity, we studied structure-activity relationships for nonsteroidal AR ligands through crystallography and site-directed mutagenesis, comparing bound conformations of R-bicalutamide, hydroxyflutamide, and two previously reported nonsteroidal androgens, S-1 and R-3. (rcsb.org)
  • Lung cancers with EGFR gene mutations tend to respond to treatments that specifically target the overactive epidermal growth factor receptor protein that allows cancer cells to constantly grow and divide. (medlineplus.gov)
  • Mutations of the thrombopoietin receptor gene ( MPL ) or the calreticulin ( CALR ) gene also may be the cause of primary myelofibrosis. (msdmanuals.com)
  • Design, synthesis and evaluation of modified coumarins as CB receptor ligands, Reihe: Beiträge zur organischen Synthese, Bd. (logos-verlag.de)
  • The design of the ligand is based upon 1-(3', 4'-dimethoxyphenethyl)-4-(3''-phenylpropyl) piperazine (1), a sigma1 agonist developed by Santen Pharmaceutical Co. Through a three-step synthesis, we have replaced one of the methyl groups with a diaminedithiol (DADT) chelating moiety attached through an alkyl chain (2). (umsystem.edu)
  • Herein we report initial investigations into the synthesis and glutamate receptor activity of 1,2,3-triazolyl amino acids. (ku.dk)
  • Experiments with antibodies against different receptor tail sections show that degradation of the GHR cytosolic domain precedes degradation of the extracellular GH-binding domain. (portlandpress.com)
  • A possible role for the ubiquitin-proteasome pathway in the degradation of the receptor and ligand is discussed. (portlandpress.com)
  • As a whole, these studies provide critical new insight for receptor-based drug design of nonsteroidal AR agonists and antagonists. (rcsb.org)
  • These studies provide the first crystallographic evidence of the mechanism by which nonsteroidal ligands interact with the wild type AR. (rcsb.org)
  • Antigen: KLH-conjugated synthetic peptide encompassing a sequence within human sRANK Ligand. (glucagon-receptor.com)
  • The ability of certain AhR ligands to induce regulatory T cells (Tregs) has generated interest in developing AhR ligands for therapeutic treatment of immune-mediated diseases. (oregonstate.edu)
  • These data demonstrate that the FMP assay is a sensitive method for assessing κ-opioid receptor induced hyperpolarization, and represents a useful approach for quantification of potency, efficacy and desensitization of KOR ligands. (ku.edu)
  • ligand binding potency and activation of several groups of major semi-volatile organic compounds (SVOCs) that are ubiquitously detected in indoor environments, including flame retardants such as polybrominated diphenyl ethers (PBDEs) and Firemaster 550 (FM550), and other SVOCs such as phthalates, organotins, halogenated phenols and bisphenols. (duke.edu)
  • The analysis of CGRP release data was combined with immunohistochemistry in order to study the cellular localization of CB1, cannabinoid receptor type 2 (CB2), CGRP and receptor activity modifying protein 1 (RAMP1), a subunit of the functional CGRP receptor, in the TG. (ku.dk)
  • The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. (bgu.ac.il)
  • This histidine is critical for RNA discrimination by RIG-I. Unlike RIG-I, the role of the innate immune receptor LGP2 is not well understood. (rutgers.edu)
  • A main goal of receptor-ligand kinetics is to determine the concentrations of the various kinetic species (i.e., the states of the receptor and ligand) at all times, from a given set of initial concentrations and a given set of rate constants. (wikipedia.org)
  • The total concentrations of receptor and ligands are sometimes varied systematically to estimate these constants. (wikipedia.org)
  • In a series of 16 new ligands, mainly based on the piperidine core, we selected three lead structures (, , and ) for further biological evaluation. (iasp-pain.org)
  • The Notch receptor is part of a core signalling pathway which is highly conserved in all metazoan species. (nih.gov)
  • I have a receptor embedded in a lipid bilayer. (uiuc.edu)
  • With regard to opiate receptors, neither morphine, the prototypic mu agonist, nor kappa selective agonists (bremazocine,and U-50488) substituted for ibogaine. (erowid.org)
  • Quantitative RT-PCR (qPCR) showed that in adult Tribolium, the receptor is mainly expressed in the head and much less in the hindgut and Malpighian tubules, suggesting that the inotocin/receptor couple does not play a role in water homeostasis. (lu.se)