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br Functional consequences of ADK regulation on astrocyte
2023-08-21
Functional consequences of ADK regulation on astrocyte function As outlined above (see introduction), ADK critically regulates the extracellular adenosine levels in nutlin 3 (Boison, 2006, Etherington et al., 2009). Changes in the levels of adenosine, as a result of the regulation of ADK expressi
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AdipoRon is an orally active
2023-08-21
AdipoRon is an orally active, synthetic small molecule that activates adiponectin receptor (AdipoR). It mimics the antidiabetic effects of adiponectin, exhibiting its effect through the activation of AMPK and PPARα pathways via AdipoR1 and AdipoR2, respectively (Fig. 2) [62]. AdipoR activation has r
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br Introduction Myasthenia gravis MG is an
2023-08-21
Introduction Myasthenia gravis (MG) is an autoimmune disease characterised by failure of transmission at the neuromuscular junction (NMJ). In 80–85% of myasthenia gravis patients, the disease is mediated by antibodies to the nicotinic g protein coupled receptors receptor (AChR; (Lindstrom et al.
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Tumor suppressor ARF regulates the activity of
2023-08-21
Tumor suppressor ARF regulates the activity of p53 by inhibiting the functions of Mdm2. ARF is induced by hyperproliferative signals emanating from oncogenic Ras, overexpressed c-myc, and from deregulated E2F . ARF prevents p53 degradation and leads to increased p53 function by sequestering Mdm2 to
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br Ataxia telangiectasia and Rad
2023-08-21
Ataxia–telangiectasia and Rad3 related as a therapeutic target Several concerns revolving around functional inhibition of ATR have hindered the exploitation of ATR as therapeutic target in cancer therapy and delayed the development of specific ATR kinase inhibitors. It was anticipated that pharma
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The canonical binding sites to which or contribute are
2023-08-21
The canonical Ranolazine 2HCl to which α2, α3, or α5 contribute are highly similar. Therefore, differences in ligand affinity will not be large even if a ligand makes optimal use of the small differences in the pockets. As a possible alternative approach to achieve separation of compound effects, l
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These recommendations may be useful for the future to avoid
2023-08-21
These recommendations may be useful for the future to avoid misleading reports and pairings. However, the existing literature can also hold back current research on some given orphans. Before entering into drug development or further physiological conceptual framework, these pairings should be thoro
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br The pathogenesis of AD and the targets of apelin
2023-08-21
The pathogenesis of AD and the targets of apelin Alzheimer's drugs Conclusions Introduction APJ, first identified from a human genomic library in 1993, belongs to a member of seven trans-membrane G protein-coupled receptor family. Its amino SB 203580 hydrochloride sequence has 31% homol
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Finally terbinafine is generally associated
2023-08-21
Finally, terbinafine is generally associated with a low index of toxicity and few adverse effects. In humans, only mild GI toxicity and hepatobiliary dysfunction are reported. In red-tailed hawks, oral administration of a high dose of terbinafine (120 mg/kg BW) was furthermore demonstrated to induce
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Prolonged duration of antimicrobial agents is also associate
2023-08-21
Prolonged duration of antimicrobial agents is also associated with increased risk of CDI by extending the time disruption of normal enteric flora. This emphasizes the importance for clinicians to adhere to shorter durations of therapy. Although longer durations of therapy are associated with a great
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Interestingly intermittent high doses of AKT inhibitors have
2023-08-18
Interestingly, intermittent high doses of AKT inhibitors have been shown to be a more effective strategy both clinically and pre-clinically. High doses appear to be required for induction of apoptosis and intermittent schedules overcome the low therapeutic index of these compounds. This is particula
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Altogether the situations described above clearly
2023-08-18
Altogether, the situations described above clearly impede the critical steps of drug discovery and development and the scientific process in general [14]. In conclusion, it is the opinion of these authors that many exciting lines of drug discovery (which includes those devoted to nAChR ligands) have
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The discovery of acetylsalicylic acid aspirin
2023-08-18
The discovery of acetylsalicylic Amyloid β-Peptide (1-42) mg (aspirin) in 1897 paved the way for the development of classical NSAIDs as first-line therapeutics for anti-inflammatory, anti-pyretic and analgesic therapy. Large efforts have been made in the following decades to improve the efficacy and
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br Author contributions br Competing
2023-08-18
Author contributions Competing interests Transparency document Acknowledgments This research was funded by a TOP ZonMW grant (40-00812-98-10054) to R.O.E., a DFG grant (KR4391/1-1) and IZKF Erlangen grant (J36) to A.K. and supported in part by Centro de Investigación Biomédica en Red de
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The Kelch like ECH associated protein Keap
2023-08-18
The Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway functions as one of the key regulator of the cellular defense system against oxidative stress [26]. Nrf2 is a redox-sensitive transcription factor, that is sequestered in the cytoplam by binding to Keap1; however, under oxidative
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