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br Allosteric inhibitors In general candidate drugs that bin
2019-08-16
Allosteric inhibitors In general, candidate drugs that bind to a GPCR at a site that is distinct (allosteric site) from the binding site of the endogenous agonist (orthosteric site) are attracting increasing attention 39, 42, 58. Allosteric modulators display saturability of their effect, probe d
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Epac proteins consist of a carboxyl terminal
2019-08-16
Epac proteins consist of a carboxyl-terminal catalytic region and an amino-terminal regulatory region, which harbors one cAMP-binding domain in Epac1 and two in Epac2 [22], [32], [51]. In the absence of cAMP, the regulatory region covers the CDC25-homology domain and autoinhibits Epac\'s enzymatic a
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Although it was shown that IL signaling induces expression o
2019-08-16
Although it was shown that IL-23 signaling induces expression of T17 pathogenic signature genes through activation of STAT3,, transcription factors other than STAT3 are also implicated for induction of pathogenic T17 cells because IL-6, which activates STAT3 similarly to IL-23, cannot induce IL-23R
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The imaging and biochemical data presented here
2019-08-16
The imaging and biochemical data presented here demonstrated that in T cells, AEP played a specific function in cleaving Foxp3 but not Tbet. These results are in accordance with previous AEP studies where it has been shown that AEP substrates in part are not amenable to other protease activity. In a
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DDR is one of two non integrin tyrosine
2019-08-16
DDR1 is one of two, non-integrin tyrosine kinase receptors activated by collagen. Although DDR1 has five isoforms (1a, 1b, 1c, 1d, 1e) generated by alternative splicing, only DDR1a and 1b have active kinase domains, whereas DDR2, encoded by a distinct gene, has one isoform (Vogel et al., 2006). Coll
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Due to the high attractiveness of E and
2019-08-16
Due to the high attractiveness of E2 and E3 ligases as drug targets, a number of drug discovery assays have been published, based on detection by fluorescence (Dudgeon et al., 2010, Krist et al., 2016, Zhang et al., 2004), CGP 55845 hydrochloride (Davydov et al., 2004, Huang et al., 2005, Kenten et
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The focus of this review
2019-08-16
The focus of this review is on the diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) enzymes, DGAT1 and DGAT2, that catalyze the esterification of a fatty acyl moiety to a DAG molecule to produce TAG. These enzymes commit DAG to being stored as TAG rather than being diverted for the synthesis of ph
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Recently we have demonstrated that the synthesis of cysteiny
2019-08-16
Recently we have demonstrated that the synthesis of cysteinyl-LTs from LTA4 by human umbilical vein endothelial cells (HUVECs) is directly associated with the activation of the CysLT2 receptor (CysLT2R) in a typical autocrine fashion, and that solely the CysLT2R is responsible for the increase in in
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TMC647055 Choline salt In the pleural exudates which
2019-08-16
In the pleural exudates, which reflect the in vivo conditions, the concentrations of CysLTs and PGE2 were quite similar. However, when cancer TMC647055 Choline salt were cultured for 24 h, both analyses of cell culture medium and cell incubations with Ca2+ ionophore showed low levels of CysLTs. In
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Substitutions on the benzene ring of
2019-08-16
Substitutions on the benzene ring of the phenyl acetic Molidustat moiety were evaluated to study their effect on DP and CRTH2 selectivity (). Compound has strong affinity for CRTH2, but it only has moderate affinity for DP. Small substitutions such as methoxy () and fluorine () next to the aryloxy
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This review focuses on the atomic basis of
2019-08-16
This review focuses on the atomic basis of CRM1-mediated nuclear export. There are now 27 crystal structures of CRM1 in the Protein Data Bank (PDB) (www.rcsb.org) [64]. Collectively, this large body of work explains various aspects of CRM1 function. Here we summarize the structure–function studies t
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br Acknowledgments br Introduction Understanding the charact
2019-08-16
Acknowledgments Introduction Understanding the characteristics of the Amazonian Dark soils “Terras Pretas de Índio” (TPIs) is of ecological importance, because the TPI soils represent a residue-based model for tropical sustainable agriculture (Sombroek et al., 2003, Neves et al., 2003, Cohen-O
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Oysters belong to the second largest animal phylum Mollusca
2019-08-15
Oysters belong to the second largest animal phylum Mollusca, and they are globally distributed aquaculture animals (Wang et al., 2018). A number of studies have demonstrated that oysters have evolved an integrated and complex innate immune system to recognize and eliminate various invaders. An array
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The folate pathway plays an essential role
2019-08-15
The folate pathway plays an essential role in cell survival by generating 5, 10-methylene tetrahydrofolate as a one-carbon donor for the synthesis of deoxythymidine monophosphate (dTMP), purines, methionine and histidine. Disruption of this pathway leads to the critical deficiency of these key molec
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Drug drug interactions are frequently attributed to function
2019-08-15
Drug-drug interactions are frequently attributed to functional alterations in CYP enzymes, including inhibition and induction (Chen et al., 2014, Wang et al., 2013). Mechanism-based inhibition is an irreversible form of enzyme inhibition and could form a stable inhibitor-enzyme complex, which is tho
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