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Modulating the ability of tumor cells
2023-08-18
Modulating the ability of tumor molar calculator to detoxify ROS is a key mechanism by which cysteine metabolism affects tumor cell survival. One study observed hypermethylation of cysteine dioxygenase (CDO1) in 60% of tested breast cancer samples, leading to increased ROS detoxification and tumor c
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Our initial approach to identify hits was two pronged and
2023-08-18
Our initial approach to identify hits was two-pronged and included a high-throughput screening (HTS) campaign of the OSI TP-0903 mg library as well as a virtual screening (VS) campaign, utilizing a publically available crystal structure of ACK1 (PDB code: ). A tolerance for protein flexibility was
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Axl has been reported to mediate cell cell adhesion
2023-08-18
Axl has been reported to mediate cell-cell adhesion and sphere-growth [11], [18] and to be important for metastasis to secondary organs [12], [14], [20]. We found an Axl-dependent CCRCC-ability of sphere-formation and repopulation after non-adhesive growth. Axl-inhibited cells could not attach to ea
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Over the past decade extensive research
2023-08-18
Over the past decade, extensive research has been directed toward the discovery of Aurora-selective small-molecule inhibitors. As a result, a handful of Aurora inhibitors has been identified. Among them, 1 (VX-680) and 2 (SNS-314) have entered human clinical trials as pan-Aurora kinase inhibitors (F
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Expression subcellular localization transcriptional activity
2023-08-18
Expression, subcellular localization, transcriptional activity and protein stability of Foxo are regulated by proteins such as STAT3, PKB, JNK and AMPK (Sun et al., 2017; Zhang et al., 2011). STAT3 is a member of the signal transducer and activator of transcription (STAT) protein family that plays c
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When a clinician diagnoses a
2023-08-17
When a clinician diagnoses a person with AD, the person is transformed into a patient with the disease. The person is a member of a patient group associated with behaviors, abilities, and experiences related both formally and informally to the diagnosis [10]. The diagnostic label implies what signs
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Interestingly all of the ROS rearrangements share a constant
2023-08-17
Interestingly, all of the ROS1 rearrangements share a constant breakpoint in ROS1 and the fusion product contain the kinase domain resulting in aberrant ROS1 expression with constitutive kinase activity. Intrachromosomal deletions and interchromosomal translocations have demonstrated the existence o
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br Aldehyde sensors to monitor substrate
2023-08-17
Aldehyde sensors to monitor substrate levels Previous efforts to ameliorate metabolic diseases frequently relied on biochemical methods which could measure the levels of toxic substrates in Poziotinib or bodily fluids (blood and serum or plasma, urine, cerebrospinal fluid). Therapeutic efforts t
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br Conclusion The HT receptor family is complex and one
2023-08-17
Conclusion The 5-HT receptor family is complex, and one may ask as does Bryan Roth et al. [205] whether this is useless N6-Methyl-dATP (i.e. too much redundancy) or an embarrassment of the riches (i.e. many potential targets to choose from to affect normal or pathological function); molecular bi
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Unlike AK inhibition the inhibition of ADA activities by EHN
2023-08-17
Unlike AK inhibition, the inhibition of ADA activities by EHNA had little effect on spinal reflex potentials, although EHNA did increase extracellular adenosine levels. One explanation for this discrepancy is that the adenosine increase seen herein was not sufficient to inhibit reflex potentials. In
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br Patients and methods The severity of
2023-08-17
Patients and methods The severity of disease documented at each outpatient visit was graded according to the modified Osserman classification: grade I, focal disease (e.g. restricted to ocular muscles); grade II, generalised disease that is mild (IIa) or moderate (IIb); grade III, severe generali
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br Acknowledgements This work was supported by the
2023-08-17
Acknowledgements This work was supported by the FedEx Institute of Technology at The University of Memphis (to DLB and ALP), NSF REU CHE 1156738 (to ALP in support of RSS), and NIHCA921060 (to GT). This material is based upon work supported by the National Science Foundation under Grant No. CHE-1
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Here we report discovery of highly selective pan Aurora kina
2023-08-17
Here we report discovery of highly selective pan-Aurora kinase inhibitors through phenotypic screening. The co-crystal structure of meclofenamate bound in the ATP binding site of Aurora A is described, and provides insight into the possible structural basis for the selectivity of the interaction.
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In the nineties we knew that baclofen
2023-08-17
In the nineties we knew that (-)baclofen was the stereo-selective ligand for the GABAB receptor which had been recognised by Norman Bowery as a receptor for GABA, which was different from the GABAA receptor (Hill and Bowery, 1981). GABAB receptor antagonists were also synthesised and made available
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Crystal structures were obtained of
2023-08-17
Crystal structures were obtained of sulfonamide 18 and amide 19 as a derivative of amide 36 (Fig. 7A and B). The precise rotameric orientation of amide 36 was of significant interest to understand the compound's interaction with the protein. As it would be difficult to assign the rotomer of 36, the
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