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Phenformin The Y H D A variant was resistant to
2021-10-28
The Y56H/D168A variant was resistant to all tested PIs, and the inhibitor binding mode determined the molecular mechanism of resistance. Prior to the development of grazoprevir, PIs typically contained large heterocyclic P2 moieties that strongly interacted with S2-subsite residues (Ali et al., 2013
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In the H NMR spectrum two pairs of doublet resonances
2021-10-28
In the 1H NMR spectrum two pairs of doublet resonances arising from the protons in the aromatic moiety of the two diastereoisomers can be readily observed around 7.5–7.6 ppm. These resonances can be used to detect and quantify the two diastereoisomers. From the results presented in Fig. 1A it can be
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The number of small molecule GSK inhibitors is continuously
2021-10-28
The number of small molecule GSK-3 inhibitors is continuously rising and many have been tested in animals. These studies have provided additional support for specific roles of GSK-3 in neuronal functions under both normal and pathological conditions. Inhibition of GSK-3 has profound effect on neurop
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br Funding M I is supported by European
2021-10-28
Funding M.I. is supported by European Research Council (ERC) Consolidator Grant 725038, Italian Association for Cancer Research (AIRC) Grant 19891, Italian Ministry of Health (MoH) Grant GR-2011-02347925, Lombardy Foundation for Biomedical Research (FRRB) Grant 2015-0010, the European Molecular B
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Through the analysis of various synthetic GPR agonists
2021-10-28
Through the analysis of various synthetic GPR40 agonists as reported in literature, we found that a number of these compounds contained a phenylpropanoic Dantrolene, sodium salt motif which was inspired from naturally occurring medium to long chain fatty acids. For instance, in the early period of
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neuropeptides br Introduction When human red blood cells hRB
2021-10-28
Introduction When human red blood neuropeptides (hRBC) are suspended in depolarising Ringers, they respond by opening a non-selective voltage-dependent cation pathway, the NSVDC channel, which is permeable to mono- and divalent cations [1], [2], [3]. In patch clamp experiments on excised hRBC ins
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(-)-Bicuculline methiodide synthesis Comparison of dlGALRs d
2021-10-28
Comparison of dlGALRs deduced amino (-)-Bicuculline methiodide synthesis sequences with that of human GALRs demonstrate that the GALR1 ortholog sequences have diverged less than those of GALR2. Since often duplicate genes undergo divergent evolution through sub-functionalization, loss or gain of new
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Recently they reported an enyne chemotype agonist
2021-10-28
Recently, they reported an enyne chemotype agonist (21, Fig. 13) with low lipophilicity, small polar surface area (PSA) and high potency (Clog P=3.8, tPSA=37 A2, EC50=20nM), further derived from TUG-424. The compound endowed fast oral GSK 0660 (tmax=15min) and a decent pharmacokinetic profile, a sat
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The knowledge that piroxicam competes with ligands that bind
2021-10-28
The knowledge that piroxicam competes with ligands that bind to FPR may be of importance for a deeper understanding of the anti-inflammatory effects possessed by this NSAIDs. It has recently been reported that not only phagocytes but also platelets express FPR on their cell surface and that these re
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In cardiomyocytes mechanical stress builds up via
2021-10-28
In cardiomyocytes mechanical stress builds up via FAs and the related costamere structures, and excessive stress can cause cardiac hypertrophy. Cardoso et al. (2016) report a comprehensive study that demonstrates the link between stress-induced FAK activation and a FAK-mediated initiation of a trans
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Focal adhesion kinase Fakir et al also known as
2021-10-28
Focal adhesion kinase (Fakir et al., 2006), also known as non-receptor tyrosine kinase (PTK2), is a 125-kDa protein that regulates cell migration, adhesion, proliferation, and survival (Tavora et al., 2014; Yang et al., 2016; Tian et al., 2017). Many studies have observed FAK overexpression and/or h
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The present findings demonstrate for the first time in
2021-10-28
The present findings demonstrate for the first time in immature rats that hippocampal infusion of ET-1 results in a rapid and long-lasting decrease in regional cerebral blood flow (rCBF) and oxygen saturation (pO2). These data are in accord with the results of studies and adult animals, which have s
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A subsequent modeling study by a different group
2021-10-27
A subsequent modeling study by a different group was based on the bovine rhodopsin homology model using the 1L9H construct [38]. However, the site-directed mutagenesis data and docking suggested that the niacin-binding pocket is different to that described in the aforementioned report, but similar t
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Molecular modeling studies also revealed insignificant diffe
2021-10-27
Molecular modeling studies also revealed insignificant differences in ligand-receptor interaction energies between R and S enantiomers of LPCs or their 2-OMe-analogues, suggesting that enantiomers of a particular structure should exert similar GPR119-mediated biological effect. Indeed, when studied
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Many studies support that the increase
2021-10-27
Many studies support that the increase of P4 improves embryonic survival and reduces embryonic losses in ruminants [6,[18], [19], [20]]. However, experimental results are variable, contradictory and often inconclusive results. Certain studies showed that administration of GnRH or hCG after artificia
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