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Of the acidic hydroxyazoles involved hydroxypyrazole had the
2020-12-18
Of the acidic hydroxyazoles involved, hydroxypyrazole had the weakest acidic profile (pKa in the range of 6–7), although highly deprotonated at physiological pH. During hit optimization, the two pyrazole ring positions available for substitution provide an opportunity for a better exploration of the
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br Introduction Plasmodium falciparum malaria
2020-12-18
Introduction Plasmodium falciparum malaria continues to be a major global cause of mortality and morbidity. Malaria treatment and control has been complicated by the emergence of resistance to widespread antimalarial drug use. The most common method for measuring antimalarial resistance is estima
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br Results br Discussion Prostate cancer dissemination and
2020-12-18
Results Discussion Prostate cancer dissemination and skeletal metastases represent major therapeutic challenges. Once the skeletal metastasis occurs, the incurable patient could just be symptomatically treated to alleviate the pain. Therefore it is of great necessity to disclose the molecular
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br Conflict of interest br Acknowledgements This
2020-12-17
Conflict of interest Acknowledgements This work was supported by the Biotechnology Research Center, China Three Gorges University, Yichang, China (No. 2016KBC05), the National Natural Science Foundation of China (No. 31370600 and 31300508), the Zhejiang Science and Technology Major Program on
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Midazolam oral clearance is used for characterization of
2020-12-17
Midazolam oral clearance is used for characterization of both intestinal and hepatic CYP3A activity. However, the identification and subsequent use of metabolic markers of CYP3A activity can eliminate the need for unnecessary administration of probe drugs such as midazolam. Such metabolic markers wo
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Introduction The first reference to a possible involvement o
2020-12-17
Introduction The first reference to a possible involvement of orexins in the effects of drugs of abuse appeared in 2003 and showed that orexigenic peptide neurons respond to the chronic administration of morphine followed by abrupt withdrawal symptoms caused by opioid receptor antagonists (Georgesc
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The synthesis of tricyclic analogs is described in Scheme
2020-12-17
The synthesis of tricyclic analogs 28–33 is described in Scheme 3. Oxidative C–C bond cleavage of the terminal olefin of 39i afforded a tricyclic product 52 without isolation of an aldehyde expected as an intermediate. Aminolysis of the chloride 52 with optionally substituted anilines afforded 28–30
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Among the other mediators which have been reported
2020-12-17
Among the other mediators which have been reported to play a role in erection are prostaglandins (PGs). Several studies have reported that alprostadil- synthetic PGE1- showed high efficacy in management of erectile dysfunction as it induces corpus cavernosal relaxation. Alprostadil has been first de
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Although the control group and tinnitus group do not signifi
2020-12-17
Although the control group and tinnitus group do not significantly differ based on age, gender or hearing loss, a limitation of this study is that the control group is only group-matched, and not individually matched. Furthermore, we only tested hearing acuity in tinnitus patients via standard pure
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A number of chemical strategies have
2020-12-17
A number of chemical strategies have been developed to design activatable optical imaging probes and have been summarized in several excellent reviews 11., 12., 13., 14., 15.. Fluorogenic enzyme substrates are one of the most explored activatable probe types for enzyme detection. These probes contai
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br Acknowledgements br Introduction Three
2020-12-17
Acknowledgements Introduction Three structurally related fungal metabolites have been isolated from chloroform extracts of submerged rice cultures of Aspergillus terreus 23-1 from stored unhulled rice in Taiwan; these were named territrems A–C to indicate their biological origin (A. terreus) a
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br Guidance of B cell localization by
2020-12-17
Guidance of B cell localization by EBI2 EBI2 expression and B cell disease Although chemoattractant receptors of the GPR family play essential roles in coordinating the migration of lymphocytes for efficient responses against pathogens, their dysregulation can result in the initiation or progr
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Other GPCRs notable for changes in expression on CLL
2020-12-16
Other GPCRs notable for changes in expression on CLL cells include upregulation of the thromboxane A2 receptor TBXA2R mRNA [61] and up and downregulation of mRNA and protein from the neurotensin receptors NTSR2 and NTSR1, respectively [62]. The Eμ-TCL1 mouse model of CLL has been used to study mult
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TTNPB Introduction Ubiquitylation is a post translational mo
2020-12-16
Introduction Ubiquitylation is a post-translational modification which impacts almost every biological process in the cell. Dysregulation of the ubiquitylation pathway is associated with several diseases, including cancer, neurodegenerative disorders, and immunological dysfunctions. Single ubiquiti
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br Significance Dysregulation of dopamine homeostasis contri
2020-12-16
Significance Dysregulation of dopamine homeostasis contributes to Parkinson's disease (PD). The nuclear receptor Nurr1 plays a central role in dopamine homeostasis, regulating the transcription of LY3023414 governing the synthesis, packaging, and reuptake of dopamine. Efforts to capitalize on Nu
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