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Small kinase inhibitors have been developed
2024-05-18

Small kinase inhibitors have been developed to block AXL by interacting with the kinase cytoplasmic ATP binding site. Up to date, no AXL selective kinase inhibitors are marketed. As depicted in , some marketed kinase inhibitors such as Bosutinib and Cabozantinib or kinase inhibitors in clinical pha
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Having established the structural requirements
2024-05-18

Having established the structural requirements for potency in both the biochemical and biomarker (CRA) assays, we evaluated key compounds in the metabolic stability assay. Disappointingly, we found that all compounds had high intrinsic clearances in mouse microsomes. To ascertain whether the in vitr
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In this study we observed the ATPase activity of RaGroEL
2024-05-18

In this study, we observed the ATPase activity of RaGroEL at various temperatures and metal ions conditions and the role of GroES in the ATPase activity of RaGroEL. Furthermore, we quantified the expression of groEL genes under different abiotic stresses, including temperature, pH, salt and oxygen s
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AR-A014418 Recruitment of the Rad BP
2024-05-18

Recruitment of the Rad9/53BP1 mediator to AR-A014418 involves multiple pathways (Fig. 2). In unperturbed conditions, Rad9 is already bound to chromatin via interaction between its Tudor domain and methylated histone H3 at lysine 79 [82], [83], [84], [85]. This constitutive Rad9 recruitment to chrom
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br Concluding remarks It is clear
2024-05-18

Concluding remarks It is clear that a disordered l-arginine homeostasis by changes in arginase, NOS and ADMA activity and expression, is not only vital in the chronic airway diseases, D609 and COPD, but also seems to play an important role in many co-morbidities. Unknown, however, is whether l-a
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Autocrine regulations of several adipokines e g
2024-05-18

Autocrine regulations of several adipokines (e.g., leptin and resistin) on adipocytes have been reported (Karastergiou and Mohamed-Ali, 2010, Ye et al., 2010). Several lines of evidence have shown that apelin influences adipocyte functions, such as, lipolysis and glucose uptake (Dray et al., 2008, Y
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The crucial role of AP
2024-05-18

The crucial role of AP-1 in establishing and maintaining cell type-specific gene expression programs and cell identity is further apparent during reprogramming of mouse embryo fibroblasts (MEFs) into iPSCs with either Oct4/Sox2/Klf4/cMyc (OSKM ) factors , or chemicals . Using ATAC-seq to profile ch
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In summary present evidence suggests that antimicrobial ther
2024-05-17

In summary, present evidence suggests that antimicrobial therapy for intra-abdominal sepsis can be shortened in patients exhibiting a clinical response to treatment. Hence, clinicians should use the resolution of clinical signs of infection as a guide to determine when during the 4–7-day window anti
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Another issue is that the vast majority of
2024-05-17

Another issue is that the vast majority of data from PET and CSF are from selected participants recruited through tertiary care dementia centers [176]. It is widely recognized that clinic-based participants differ from community-based studies, for example, the amount, type, and distribution of neuro
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For the time being fluorescent in situ hybridization FISH re
2024-05-17

For the time being, fluorescent in situ hybridization (FISH) remains the ‘gold standard’ for ALK rearrangements diagnosis but immunohistochemistry has become a widely used pre-screening tool and the FDA recently approved the Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ) as a com
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br AHR expression in cancer
2024-05-17

AHR expression in cancer Perhaps the earliest indicator that the AHR might play an ongoing role in tumorigenesis, independent of its role in generating mutations, was the demonstration that non-genotoxic 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD) is a carcinogen in animals and humans [7]. Althou
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br ABCA and cancer drug response Overall the expression of
2024-05-17

ABCA2 and cancer drug response Overall, the expression of ABC transporters has been linked with multidrug resistance phenotypes through the efflux of drugs via ATP-dependent transport. For example, 13 distinct transporters (ABCA2, ABCB1, ABCB4, ABCB11, ABCC1–6 ABCC10, ABCC11 and ABCG2) have been
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Numerous studies have reported high glutamate levels in the
2024-05-17

Numerous studies have reported high glutamate levels in the brains of patients with depression, indicating that the glutamate system plays a crucial role in depression (Sanacora et al., 2004; Kendell et al., 2005; Hashimoto et al., 2007). Furthermore, several clinically effective antidepressant drug
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Toxicity is the main reason for the failure at
2024-05-17

Toxicity is the main reason for the failure at all stages of the new drug development process. The major part of safety-related attrition occurs at preclinical phases while predicting preclinical safety liabilities earlier in the drug development process. This strategy enables the design and/or sele
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HT modulates cortical and hippocampal pyramidal cell
2024-05-17

5-HT modulates cortical and hippocampal pyramidal cell function in a very complex manner, since most 5-HT receptor subtypes (excitatory as well as inhibitory) are expressed on pyramidal PF-5274857 as well as GABAergic interneurons that exert inhibitory control over pyramidal cells (Leiser et al., 2
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