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#28545167   2017/05/25 Save this To Up

Synthesis of S-2-((S)-3-(4-chlorophenyl)-N'-((4-chlorophenyl)sulfonyl)-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamido)-3-(methyl-d3 )butanamide-d5 , octa-deuterated JD5037.

JD5037 (1) is a potent and selective, peripherally acting inverse agonist of the cannabinoid (CB1 R) receptor. Peripheral CB1 receptor antagonists/inverse agonists have great potential in the treatment of metabolic disorders like type 2 diabetes, obesity and NASH. We report the synthesis of octa-deuterated [(2) H8 ]-JD5037 (S, S) (8) along with its (S, R) diastereomer (13) from commercially available L-valine-d8 starting material. The [(2) H8 ]-JD5037 compound will be used to quantitate unlabeled JD5037 during clinical ADME studies and will be used as an LC-MS/MS bioanalytical standard.

1309 related Products with: Synthesis of S-2-((S)-3-(4-chlorophenyl)-N'-((4-chlorophenyl)sulfonyl)-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamido)-3-(methyl-d3 )butanamide-d5 , octa-deuterated JD5037.

5-Acetyl-6-methyl-4-pheny 3-Amino-6-bromo-4-(2-chlo 3-Amino-N-[(4-chloropheny 1,4-Dihydro-2,6-dimethyl (2S,3S)-�[2-[3-(Acetoxy 1-Acetyl-2,3-dihydro-2-me 1-Acetyl-2,3-dihydro-2-me 5-(Acetylimino)-4,5-dihyd (3E)-4-(Acetylthio)-α-(2 N-[[4-[[(4-Amino[1,1'-bip 5-[[2-Amino-5-[2-(4-chlor 2-Amino-4-chloro-N-[(1R,2

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#28545069   2017/05/25 Save this To Up

Behavioral alterations are associated with vitamin B12 deficiency in the transcobalamin receptor/CD320 KO mouse.

Vitamin B12 (cobalamin) deficiency is prevalent worldwide and causes megaloblastic anemia and neurologic deficits. While the anemia can be treated, the neurologic deficits can become refractive to treatment as the disease progresses. Therefore, timely intervention is critical for a favorable outcome. Moreover, the metabolic basis for the neuro-pathologic changes and the role of cobalamin deficiency in the pathology still remains unexplained. Using a transcobalamin receptor / CD320 knockout mouse that lacks the receptor for cellular uptake of transcobalamin bound cobalamin, we aimed to determine whether cobalamin deficiency in the central nervous system produced functional neurologic deficits in the mouse that would parallel those observed in humans. Our behavioral analyses indicate elevated anxiety and deficits in learning, memory and set-shifting of a spatial memory task in the KO mouse. Consistent with the behavioral deficits, the knockout mouse shows impaired expression of the early phase of hippocampal long-term potentiation along with reduced expression of GluR1, decreased brain mass and a significant reduction in the size of nuclei of the hippocampal pyramidal neurons. Our study suggests that the CD320 knockout mouse develops behavioral deficits associated with cobalamin deficiency and therefore could provide a model to understand the metabolic and genetic basis of neuro-pathologic changes due to cobalamin deficiency.

1876 related Products with: Behavioral alterations are associated with vitamin B12 deficiency in the transcobalamin receptor/CD320 KO mouse.

Goat Anti-Human, Mouse AR Mouse Anti-Human Interleu Goat Anti-Human, Mouse Ca Goat Anti-Rat CCKA Recept Rat anti mouse CD119 (INF Mouse anti human INF alph Mouse anti human INF gamm Sterile filtered mouse s Anti AGO2 Mouse, Monoclon Anti AGO2 Mouse, Monoclon HIV1 integrase antibody, Interferon-a Receptor Typ

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#28545052   2017/05/25 Save this To Up

BRL3 and AtRGS1 cooperate to fine tune growth inhibition and ROS activation.

Plasma membrane-localized leucine-rich repeat receptor-like kinases directly activates G protein complex via interaction with seven transmembrane domain Regulator of G-protein Signaling 1 (AtRGS1) protein. Brassinosteroid insensitive 1 (BRI1) LIKE3 (BRL3) phosphorylates AtRGS1 in vitro. FRET analysis showed that BRL3 and AtRGS1 interaction dynamics change in response to glucose and flg22. Both BRL3 and AtRGS1 function in glucose sensing and brl3 and rgs1-2 single mutants are hyposensitive to high glucose as well as the brl3/rgs1 double mutant. BRL3 and AtRGS1 function in the same pathway linked to high glucose sensing. Hypocotyl elongation, another sugar-mediated pathway, is also implicated to be partially mediated by BRL3 and AtRGS1 because rgs1-2, brl3-2 and brl3-2/ rgs1-2 mutants share the long hypocotyl phenotype. BRL3 and AtRGS1 modulate the flg22-induced ROS burst and block one or more components positively regulating ROS production because the brl3/rgs1 double mutant has ~60% more ROS production than wild type while rgs1-2 has a partial ROS burst impairment and brl3 has slightly more ROS production. Here, we proposed a simple model where both BRL3 and AtRGS1 are part of a fine-tuning mechanism sensing glucose and flg22 to prevent excess ROS burst and control growth inhibition.

2047 related Products with: BRL3 and AtRGS1 cooperate to fine tune growth inhibition and ROS activation.

Androgen Receptor (Phosph Androgen Receptor (Phosph Rabbit Anti-Human Androge Rabbit Anti-Human Androge Androgen Receptor (Ab 650 Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri AZD-3514 Mechanisms: Andr 17β-Acetoxy-2α-bromo-5 (5α,16β)-N-Acetyl-16-[2 (5α,16β)-N-Acetyl-16-ac 5α-N-Acetyl-2'H-androst-

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#28545035   2017/05/25 Save this To Up

Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells. Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.

1371 related Products with: Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

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#28544993   2017/05/25 Save this To Up

Muscarinic receptor M4 positive allosteric modulators attenuate central effects of cocaine.

Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the hypothesis that specific muscarinic M4 receptor stimulation can attenuate the discriminative stimulus effects and conditioned rewarding effects of cocaine, measures believed to predict the ability of cocaine and cocaine-associated cues to elicit relapse to drug taking.

2403 related Products with: Muscarinic receptor M4 positive allosteric modulators attenuate central effects of cocaine.

Rabbit Anti-Human Muscari Estrogen Receptor; Clone Estrogen Receptor; Clone Progesterone Receptor (P Progesterone Receptor (P Estrogen Receptor; Clone Progesterone Receptor (P Glucagon receptor Glucagon like peptide 1 r Leptin Receptor Anti VGLUT 1 Rat, polyclo Anti Rat VGLUT 2, Rabbit

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#28544984   2017/05/25 Save this To Up

Histo-blood group antigens as mediators of infections.

The critical first step of a microbial infection is usually the attachment of pathogens to host cell glycans. Targets on host tissues are in particular the histo-blood group antigens (HBGAs), which are present in rich diversity in the mucus layer and on the underlying mucosa. Recent structural and functional studies have revealed significant new insight into the molecular mechanisms, explaining why individuals with certain blood groups are at increased risk of some infections. The most prominent example of blood-group-associated diseases is cholera, caused by infection with Vibrio cholerae. Many other microbial pathogens, for example Pseudomonas aeruginosa infecting the airways, and enterotoxigenic Escherichia coli (ETEC) causing traveler's diarrhea, also bind to histo-blood group antigens, but show a less clear correlation with blood group phenotype. Yet other pathogens, for example norovirus and Helicobacter pylori, recognize HBGAs differently depending on the strain. In all cases, milk oligosaccharides can aid the hosts' defenses, acting as natural receptor decoys, and anti-infectious therapy can be designed along similar strategies. In this review, we focus on important infections of humans, but the molecular mechanisms are of general relevance to a broad range of microbial infections of humans and animals.

2040 related Products with: Histo-blood group antigens as mediators of infections.

Blood Group Antibodies a anti B human blood group MOUSE ANTI HUMAN CD173 - Blood Group Lewis a antib alpha DGal(1 4) DGal CETE Astra Blue 6GLL, Stain fo Rat monoclonal anti mouse Rat Anti-Human CD77 (bloo Anti-ASXL1(Putative Polyc Anti ASXL1(Putative Polyc Rapid Microplate Assay K Astra Blue Solution

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#28544973   2017/05/25 Save this To Up

PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitude of ensuing antibody and CD8(+) T cell responses.

The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes. The presence of PEG was shown to increase solubility with a concomitant reduction in the particle size of vaccine formulations that was dependent on the length of PEG used. When compared to non-PEGylated R4Pam2Cys, vaccination of animals with antigen-complexed PEGylated R4Pam2Cys resulted not only in improvements in antibody production but significantly higher antigen-specific CD8(+) T cell responses. Both lipopeptides exhibited similar in vitro capabilities to induce DC maturation, facilitate antigen uptake and presentation to T cells. Moreover, analyses of the transcriptomes obtained from DCs treated with either lipopeptide revealed a large number of commonly induced genes with similar transcript expression levels, suggesting that common signalling pathways and processes were engaged following activation by either lipopeptide. In vivo analysis however revealed that vaccination with antigen-complexed PEGylated R4Pam2Cys resulted in improved antigen presentation to T cells. These heightened responses were not attributed to prolonged antigen persistence but rather due to more rapid transportation of antigen from the injection site into the draining lymph nodes over a short period of time. Our results indicate that reducing the size of formed antigen-TLR2-agonist complexes by PEGylation does not compromise the activity of the agonist but in fact enhances its trafficking in vivo ultimately leading to improved humoral and cell-mediated immune responses.

2289 related Products with: PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitude of ensuing antibody and CD8(+) T cell responses.

Androstane-3a, 17b-diol 5 Androstane-3a,17b-diol Gl Androstenedione-19 Antibo Androgen Receptor (Phosph Androgen Receptor (Phosph MOUSE ANTI BORRELIA BURGD Androgen Receptor (Ab 650 TCP-1 theta antibody Sour thymic dendritic cell-der Beta Amyloid (40) ELISA K Beta Amyloid (1 42) ELISA TLR2 Antibody

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#28544923   2017/05/25 Save this To Up

Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy.

High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown.

2612 related Products with: Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy.

Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched Breast cancer and matched Breast cancer and matched High density (188 cases 2 High density (188 cases 2 Anti beta3 AR Human, Poly Breast cancer tissue arra Breast cancer (IDC) tissu Breast cancer and adjacen Breast cancer tissue arra

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#28544909   2017/05/25 Save this To Up

Can human allergy drug fexofenadine, an antagonist of histamine (H1) receptor, be used to treat dog and cat? Homology modeling, docking and molecular dynamic Simulation of three H1 receptors in complex with fexofenadine.

Fexofenadine, a potent antagonist to human histamine 1 (H1) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H1 receptor, the similar studies on non-human pet H1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H1 receptors were built based on the crystal structure of human H1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals.

1807 related Products with: Can human allergy drug fexofenadine, an antagonist of histamine (H1) receptor, be used to treat dog and cat? Homology modeling, docking and molecular dynamic Simulation of three H1 receptors in complex with fexofenadine.

Goat Anti-Human Histamine Goat Anti-Human Histamine Rabbit Anti-Human Androge Rabbit Anti-Human Androge AZD-3514 Mechanisms: Andr Rabbit Anti-Human Androge Goat Anti-Human Androgen CAR,CAR,Constitutive acti Goat Anti-Human, Mouse Ca Mouse anti human INF alph Interleukins Recombinant Recombinant Human Androge

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#28544905   2017/05/25 Save this To Up

High serum levels of soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) are associated with adverse clinical features and predict poor outcome in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with heterogeneous outcomes. To improve accuracy of the international prognostic index score, new biological variables are being investigated. The aim of this study was to determine the prognostic significance of serum levels of different cytokines, namely soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF). We analyzed 197 de novo DLBCL patients (91 M/106 F; median age 66 years) treated with immunochemotherapy in a single institution. Serum cytokine determination was performed with ELISA, using the upper normal values as cut-offs. sIL-2R, IL-6 and TNF were elevated in 133, 130 and 144 cases, respectively. Elevation of each of these cytokines correlated with worse performance status, presence of B symptoms, advanced stage, elevated LDH and β2-microglobulin (P<0.03) and lower complete remission rate (P<0.001). Elevated levels of serum sIL-2R and TNF were significantly associated with shorter progression-free (PFS) and overall survival (OS), while elevated IL-6 only with shorter PFS. Early death (<4months from diagnosis) strongly correlated with elevated cytokines. Determination of serum cytokines levels is simple and adds information regarding risk of early death, response to therapy, and outcome.

1607 related Products with: High serum levels of soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) are associated with adverse clinical features and predict poor outcome in diffuse large B-cell lymphoma.

Mouse Anti-Human Interleu Human soluble interleukin Human Interleukin-32 alph Human Interleukin-1-alpha TNFRSF1B - Goat polyclona RANK Ligand Soluble, Huma Tumor necrosis factor (TN CELLKINES Natural Human I Human Interleukin-7 IL-7 Human Tumor Necrosis Fact Human Interleukin-16 IL-1 Human Interleukin-33 IL-3

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