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Among RAS mutant tumors analyzed
2019-10-18
Among RAS mutant tumors analyzed, we found that the efficacy of either the SHP2 inhibitor SHP099, or combined MEK and SHP2 inhibition was best in those expressing RAS mutations at G12 (Figure 7B). Recent studies revealed that cellular RAS(G12C) activity depends on RTK-mediated nucleotide exchange, a
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The loss of secondary mutation
2019-10-17
The loss of secondary mutation T790M mutation after AR and SCLC transformation was also reported for Rociletinib. Piotrowska et al. using the MGH NGS platform recently reported in 13 biopsies among 12 EGFR T790M+ patients progressing after treatment with Rociletinib the loss of EGFR T790M mutation i
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E ubiquitin ligases are key players in the
2019-10-17
E3 ubiquitin ligases are key players in the ubiquitin-proteasome pathway because they catalyse ubiquitination of substrate proteins.39, 40, 41 As important regulators of cellular ubiquitination, E3 ligases are emerging as attractive drug targets, particularly in cancer.42, 43, 44 However, E3 ligases
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Benzydamine HCl The potential off target activity of against
2019-10-17
The potential off-target activity of against other ATP-dependent enzymes, such as kinases, was also investigated. Encouragingly, there was no significant inhibition of ATP binding to 97 human kinases, when was evaluated at 10μM within a DiscoveRx scanEDGE® kinome screen (, ). All together, these d
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Herein in continuation of our interest
2019-10-17
Herein, in continuation of our interest in designing new DNA photocleavage agents [18], we report the synthesis, characterization and DNA binding and cleaving properties of a novel compound: trans-N,N-dimethyl-10,11-di(pyridin-4-ium)-10,11-dihydro-9,12-dioxobenzo[e]phenanthrene tetrafluoroborate (1
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In summary these results are consistent with
2019-10-17
In summary, these results are consistent with our hypothesis that chemical nitrosation of BMAA to N-BMAA results in the formation of an alkylating agent. Furthermore, we have shown that N-BMAA is more toxic than BMAA itself. Previously, methylazoxymethanol (MAM), which is also present in the cycad n
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During host cell interactions G intestinalis
2019-10-17
During host-cell interactions, G. intestinalis trophozoites up-regulate several cell-associated proteins, including high-cysteine membrane proteins (HCMPs) and variant surface proteins (VSPs) [8]. The parasite also releases around 200 proteins upon host-cell contact, including many proteases [9,10].
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sitagliptin phosphate br Materials and methods Male
2019-10-17
Materials and methods Male Hartley guinea pigs (300–350g) were obtained from National Laboratory Animal Center, Taiwan. LTD4, LTC4, LTE4, LTB4, montelukast and BAY u9773 were purchased from Cayman Chemical, Ann Arbor, Michigan; Carbachol, atropine, l-serine, boric acid, l-cysteine and all buffer
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As the principal receptors for
2019-10-17
As the principal receptors for regulating the inflammatory process in mammals, CXCR1 and CXCR2 have an important role in regulating the trafficking of phagocytes such as neutrophils, monocytes and macrophages (Viola and Luster, 2008). The evidence gathered to date from fish studies are in agreement
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As suggested by previous data we identified that the
2019-10-17
As suggested by previous data [45], we identified that the N-terminal and C-terminal domains of DDX3 were enriched in intrinsically disordered regions (Fig. 6). We also found that this characteristic was conserved in the external domains of several homologs of DDX3 (from yeast to human) and all desc
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The most important cytotoxic lesion
2019-10-17
The most important cytotoxic lesion formed by the nitrogen mustards is generally considered to be the DNA–DNA interstrand cross-link 12, 13. DNA–DNA interstrand cross-links are thought to exert their cytotoxic effects by inhibiting DNA duplex strand separation, progression of the 22 9 fork and DNA
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Furthermore positioning the naphthalene nucleus in d
2019-10-17
Furthermore, positioning the naphthalene nucleus in 3d within the main active site and forming one hydrogen bond with Tyr385 in addition to many hydrophobic interactions with Val349, Leu352, Gly526, Ala527 and Leu531 residues, correlates well with the position and hydrophobic interactions of the tri
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This letter reports an ab initio study on the X
2019-10-17
This letter reports an ab initio study on the X peaks of PES by including the SO effect. The multiplet split energies are calculated with the SO-MCQDPT2 method [21], and the so-called pole strengths are evaluated to simulate the relative intensities. The results are compared with the experimental PE
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br Functional significance Defects of
2019-10-17
Functional significance Defects of the lysyl hydroxylases LH1, LH2, and LH3 impair collagen secretion and stability in the extracellular matrix, and cause rare connective tissue disorders such as Ehlers-Danlos type-VI [27], Bruck syndrome [28], and skeletal dysplasia [29], respectively. Elucidati
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d ap5 In some pancreatic and non pancreatic tissues
2019-10-17
In some pancreatic and non-pancreatic tissues, the chloride and calcium channels are heavily regulated by phosphorylation by protein kinases, such as PKC, cyclic AMP-dependent protein kinase (PKA), PKCaMKII, PI3K and protein tyrosine kinases [7,36,37]. Since the interaction of triterpenes with recep
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