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We further analyzed selected hit
2023-12-14

We further analyzed selected hit compounds for their ability to inhibit human AdK in intact cells. Human 1321N1 astrocytoma IKK Inhibitor VII were utilized which were found to express AdK. The whole cell assay was performed using a 96-well format. The standard AdK inhibitor 5-iodotubercidin was emp
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During the course of our
2023-12-14

During the course of our ACK1 inhibitor program, a high-throughput screening (HTS) campaign of our internal sample collection was conducted. A series of -aryl pyrimidine-5-carboxamides of the general structure () was identified. Earlier studies of the structure–activity relationship (SAR) of ident
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The role of DHT in early teleost embryogenesis
2023-12-14

The role of DHT in early teleost embryogenesis is not entirely clear or established, however additional studies that treat fish embryos to DHT or to specific srd5a inhibitors at critical stages of development (i.e. prior to sex differentiation) will shed light on the early functions of this androgen
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Aldose reductase AR is an
2023-12-13

Aldose reductase (AR), is an NADPH-dependent aldo-keto reductase very well studied as a catalyst of glucose conversion to sorbitol in the polyol pathway [11], [12]. In the diabetic lens characterized by chronically high levels of glucose, AR is responsible for production of high levels of sorbitol a
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Glucose permeability studies demonstrated a high glucose
2023-12-13

Glucose permeability studies demonstrated a high glucose flux through the SF films used in the present work. Recent diffusion studies, including small molecular drugs and oxygen permeation through SF membranes [32], further support the quality of SF and its possible application as a material for bio
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Finally we show that the optimal corporate tax
2023-12-13

Finally, we show that the optimal corporate tax rate is strictly positive, balancing the increase in tax revenues against the loss in consumer surplus due to higher prices and fewer firms (products). This result is related to the well-known “excessive entry theorem” that shows, for a large class of
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Optimization of the B ring specifically targeted preventing
2023-12-12

Optimization of the B-ring specifically targeted preventing the oxidation of the ring system (). As described above, the 4-position of the phenyl ring provides the appropriate vector towards bulk solvent. - and -linked substitutions at the 4-position of the B-ring from the 4-fluoro-nitrophenyl inter
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crizotinib Further analysis sought to understand the mechani
2023-12-12

Further analysis sought to understand the mechanism associated with the autotaxin-mediated increase of miR-489-3p in circulation. Based upon sequence complementarity, DIANA TarBase predicted miR-489-3p targets MAPK2K1, or MEK1, an oncogene widely dysregulated in cancer (Fig. 4A). To test this relati
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br Concluding Remarks and Future Directions The physiologica
2023-12-12

Concluding Remarks and Future Directions The physiological significance of autophagy in neuronal function is steadily emerging. The studies discussed herein reveal that key neuronal functions, such as neurotransmitter release, pruning of dendritic spines, and behavioural outputs of neural network
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br Concluding remarks Autophagy ensures cell homeostasis and
2023-12-12

Concluding remarks Autophagy ensures cell homeostasis and survival through the continuous degradation/recycling of intracellular components. It can also represent a conserved, cell-intrinsic, defense mechanism against invading pathogens, including viruses. The autophagy process can be activated r
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br Conclusion In summary screening a small compound library
2023-12-12

Conclusion In summary, screening a small compound library based on the 3-aminopyridin-2-one motif in a target-blind manner against a 26-kinase panel, representative of the kinome, identified hits that possess good activity and excellent ligand efficiency against MPS1, Aurora A and Aurora B. The b
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Among the most important Ca regulatory mechanisms are
2023-12-12

Among the most important Ca regulatory mechanisms are the Plasma Membrane Calcium ATPase (PMCA) and Sarcoplasmic Reticulum Calcium ATPase (SERCA). These pumps belong to the family of P-ATPases, which share the formation of an acid-stable phosphorylated intermediate as part of their reaction cycle. P
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Upregulation of ACLY is common in many cancers Kuhajda
2023-12-12

Upregulation of ACLY is common in many cancers (Kuhajda, 2000, Milgraum et al., 1997, Swinnen et al., 2004, Yahagi et al., 2005). This is in part due to the transcriptional activation by SREBP-1 resulting from the activation of the PI3K/AKT pathway in cancers (Kim et al., 2010, Nadler et al., 2001,
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ketorolac toradol Apelin is a peptide hormone and
2023-12-12

Apelin is a peptide hormone and an endogenous ligand for a G protein-coupled receptor named APJ [7], [8], and apelin and APJ are widely expressed in human organs including hypothalamus, heart, lungs, kidneys, adipose tissue, muscles, and others [9]. Apelin is initially synthesized as a 77-amino-acid
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In glucose stimulated pancreatic cells B Raf activity
2023-12-12

In glucose-stimulated pancreatic β-cells, B-Raf activity is increased, while Raf-1 activity is under the detection limit (Duan and Cobb, 2010). Thus, B-Raf is the primary protein kinase involved in the rapid activation of ERK1/2 in glucose-treated pancreatic β-cells. Expression of a dominant-negativ
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