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Almost of drugs in the market undergo
2020-11-25
Almost 75% of drugs in the market undergo deactivation though oxidation, reduction or hydrolysis by cytochrome P450 (CYP) enzymes, and then, either directly or by facilitated excretion from the body (Guengerich, 2008). The CYP3A subfamily is of particular interest because of its broad substrate spec
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Ung et al examined a variety of structural features
2020-11-25
Ung et al. examined a variety of structural features based upon the location of the DFG-motif and the αC-helix to define the conformational space of the catalytic domain of protein kinases [75]. They reported that the DFG motif can move from its active DFG-Din location to the inactive DFG-Dout locat
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phosphocreatine mg br Materials and methods br Results br
2020-11-25
Materials and methods Results Discussion CDK4 has been identified recently as a potential therapeutic target in human breast cancer, liposarcoma, melanoma, and glioblastoma [[37], [38], [39]]. Due to the importance of CDK4 activity in cancer cells, CDK4 inhibitors have emerged as promising
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Besides the regulation of the stress responses CRF and the
2020-11-24
Besides the regulation of the stress responses, CRF and the urocortins have been implicated in drug addiction (Bruijnzeel and Gold, 2005, Sarnyai et al., 2001). For instance nicotine, the addictive substance of tobacco, can activate the HPA axis, just like any other stressor may do, although its imp
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Among the various neurotransmitter systems pointed out to pl
2020-11-24
Among the various neurotransmitter systems pointed out to play a role in the mediation of defensive and antinociceptive responses elicited by environmentally aversive stimuli, the neuropeptide corticotropin-releasing factor or hormone (CRF or CRH) has attracted the interest of many researchers inves
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As shown in Figs a and b with the
2020-11-24
As shown in Figs. 3(a) and (b), with the SO effect, the absolute values of the VDEs change by at most 0.19eV. Table 1 also shows that the observed peak splitting energies in the Sm-Ho complexes were reproduced even without the SO effect. Considering its significant importance in the electronic struc
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To better understand the mechanism of splicing
2020-11-24
To better understand the mechanism of splicing in CLCN1, we began by constructing a minigene spanning exons 5–7 of CLCN1, resulting in the synthetic CLCN1 (5–7) minigene. We also established a new assay using real-time reverse transcription (RT)-PCR, which can distinguish between splicing variants b
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Introduction Primitive neuroectodermal tumors PNETs are mali
2020-11-24
Introduction Primitive neuroectodermal tumors (PNETs) are malignant, small round cell tumors of neural crest origin which typically arises from bone or soft tissue in the trunk/axial skeleton/paraspinal regions in adolescents and young adults and comprises of 50% cases with local recurrence and met
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br Conflicts of interest br
2020-11-24
Conflicts of interest Acknowledgements This work was supported, in part or in whole, by the grants from the National Natural Science Foundation of China (11802056, 11772088), the China Postdoctoral Science Foundation (2018M640904), and the Fundamental Research Funds for the Central Universitie
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Our previous high throughput screening HTS
2020-11-24
Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based ap1 assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20], [21], [22], [23], [24]
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Biochemically the primary function of PPIP K is kinase media
2020-11-24
Biochemically, the primary function of PPIP5K2 is 1-kinase-mediated phosphorylation of 5-IP7 to form 1,5-IP8 (Shears, 2018). To a lesser extent, PPIP5K2 also phosphorylates IP6 to produce 1-IP7. Furthermore, PPIP5K2 has been shown to catalyze a reverse reaction, that is, dephosphorylation of 1,5-IP8
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br Introduction Rheumatoid arthritis RA is a chronic
2020-11-24
Introduction Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that can be divided in at least two subsets based on the presence of antibodies to citrullinated proteins (ACPAs) [1]. Importantly, such ACPA target proteins [[2], [3], [4], [5]] also represent candidate autoantige
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To further confirm the roles of the CYP enzymes involved
2020-11-24
To further confirm the roles of the CYP450 enzymes involved in the metabolism of Dip in rat liver microsomes, we utilized not only chemical inhibitors but also a correlation analysis and a panel of recombinant rat CYP450 enzymes to evaluate the contribution of CYP450 enzymes. The results of the corr
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UCB 35625 Neuronal cells have highly developed ER which make
2020-11-24
Neuronal UCB 35625 have highly developed ER, which makes them susceptible to loss of ER function following exposure to various agents, which leads to apoptosis (Lindholm et al., 2006, Katayama et al., 2004). Multiple pathways may be involved in ER stress-initiated apoptosis. Among them, the PKR-lik
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BRD 7552 The LNX ligand of numb protein
2020-11-24
The LNX (ligand of numb protein-X) or PDZRN (PDZ and RING) family of proteins consists of five members (LNX1–LNX5), the first four of which act as E3‐ubiquitin ligases in various roles, as reviewed elsewhere [14]. LNX proteins comprise a RING domain and two to four PDZ (PSD-95, DlgA, ZO-1) domains [
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