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UNC 0631 of Classical DHFR inhibitors such as methotrexate
2019-07-10
Classical DHFR inhibitors such as methotrexate (MTX) bind tightly to the enzyme and possess adequate clinical pharmacokinetics. MTX bind to the DHFR binding site through the formation of hydrogen bonds with Asn64, Lys68, Arg28, Arg70, Val115 and Ile7 amino UNC 0631 of residues as well as hydrophobi
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br Introduction Analyses of genomic alterations in cancer
2019-07-10
Introduction Analyses of genomic alterations in cancer have identified epidermal growth factor receptor (EGFR) as one of the most potent “oncogenic driver” kinases that is present in many epithelial tumors including endometrial, breast, prostate, skin, esophagus, lung, stomach, colorectal, and re
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br Acknowledgments Denise Fernandes acknowledges
2019-07-10
Acknowledgments Denise Fernandes acknowledges a postdoc fellowship (SFRH/BPD/34289/2006) from the Portuguese Fundação para a Ciência e Tecnologia (FCT) of the Ministry of Science and Technology of Portugal. This work was supported by the Spanish National Plan for Research (Project Ref. CGL2011-24
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Based on our studies presented above
2019-07-10
Based on our studies presented above, atipamezole can be used as a new in vitro and in vivo tool GSK 0660 as a pan-CYP inhibitor for CYP mediated metabolism study. It carries many unique characteristics compared to ABT which is currently being widely used for this purpose. These new characteristics
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The new ESC guidelines incorporate data from a
2019-07-10
The new ESC guidelines incorporate data from a network meta-analysis of 100 studies confirming that new-generation drug-eluting stents (DES) improve survival compared with medical treatment, although this has not been demonstrated in any individual study. REVASCULARIZATION IN NON–ST-ELEVATION ACU
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br Acknowledgements This study is sponsored
2019-07-10
Acknowledgements This study is sponsored by the Natural Science Foundation of China (grant no. 51178161), 111 Project (grant no. B13024) and the Fundamental Research Funds for the Central Universities (grant no. 2017B00914) Introduction Highway and pavement engineers are facing concrete pavem
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The presence of a vicious cycle
2019-07-10
The presence of a “vicious cycle” established between tumor proliferation and paratumor osteolysis plays a crucial role in the development of primary bone tumors [53]. Cancer cells produce soluble factors that activate directly or indirectly via osteoblasts, osteoclast differentiation and maturation
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Three kinase inhibitors dasatinib type I imatinib
2019-07-09
Three kinase inhibitors dasatinib (type I), imatinib (type II) and nilotinib (type II), identified initially as inhibitors of tyrosine kinase BCR-ABL, were found to target DDRs in a chemical proteomic profiling study (Bantscheff et al., 2007, Hantschel et al., 2008). These tyrosine kinase inhibitors
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bombesin receptor Valproic acid VPA is a
2019-07-09
Valproic bombesin receptor (VPA) is a first-line treatment for epilepsy and bipolar disorder, although its therapeutic mechanism of action is not fully understood. Considerable evidence suggests that VPA can act through the GABAergic system, NMDA receptors, and/or sodium channels (for review, see L
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br Materials and methods br
2019-07-09
Materials and methods Results Discussion We initially found that ISL, a natural product with a linear scaffold (2-propenone), is able to inhibit CK2 (IC50 = 17.3 μM). Then we have investigated the inhibitory potential of a novel series of compounds with linear scaffolds by combining fragmen
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The major concern of PDE I use
2019-07-09
The major concern of PDE-5-I use in liver cirrhosis is the potentially harmful effect on systemic blood pressure. Data of clinical studies are conflicting [27], [30], [31], [32], but available patient details suggest that in advanced liver cirrhosis, PDE-5-Is lower systemic blood pressure to a great
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br The estrogen receptors History and discovery In
2019-07-09
The estrogen receptors: History and discovery In 1958, Elwood Jensen discovered the estrogen receptor, the first receptor ever encountered for any hormone, by showing that reproductive female tissues were able to uptake estrogen from the circulation by binding to proteins. He later demonstrated t
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The effect of transformation of the linker
2019-07-09
The effect of transformation of the linker Y between the carboxylic HS-173 of residue and the phenyl moiety of 2b was also investigated, and is illustrated in Table 5. Analogs 2b, 16, and 17, possessing conformationally restricted carboxylic acid residues, tended to show stronger antagonist activity
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Using the juxtarenal PPE the induction
2019-07-09
Using the juxtarenal PPE, the induction of juxta- and suprarenal aneurysms is described herein (Fig. 3A). The infra-/suprarenal part of the ML324 molecular can now be investigated separately, taking into account different embryological backgrounds and varying reactivity to differing stimuli (review
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ER redox imbalance leads to the
2019-07-09
ER redox imbalance leads to the accumulation of misfolded proteins, which might trigger the unfolded protein response (UPR) [17]. In the initiation of UPR, GRP78 preferentially binds to unfolded proteins, shifting the binding equilibrium away from IRE-1, PERK, and ATF-6, the initiators of UPR [18].
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