• We are pursuing a hit to lead

  2022-06-23

  

  We are pursuing a hit-to-lead medicinal chemistry campaign to optimize inhibitors of the HBV RNaseH. Here, we report the activity of seven new HIDs and nine new HPDs, with significant improvements in in vitro potency and cytotoxicity profiles for the HPD compounds. Materials and methods Result

• In this study we demonstrate that

  2022-06-23

  

  In this study, we demonstrate that HHcy upregulated the expression of GSNOR in T cells. As a result, GSNOR induced denitrosylation of Akt in Hcy-activated T HC-030031 in vivo and in vitro, which contributed to vascular inflammation and susceptibility to atherosclerosis in GSNOR-/-ApoE-/- mice. The

• Several studies have found that GPR

  2022-06-23

  

  Several studies have found that GPR55 possesses a distinct pharmacology from that of CB1 and CB2, and that only certain cannabinoids act at this receptor. In transfected AS-252424 expressing hGPR55, out of more than 20 synthetic and endogenous cannabinoids evaluated, only 2 compounds, SR141716A (Rim

• Because of its excellent GPR potency good hERG selectivity a

  2022-06-23

  

  Because of its excellent GPR119 potency, good hERG selectivity and favorable rat t, hcv protease inhibitors was scaled-up and further profiled. The synthetic protocols described in , were both suitable for a multi-gram scale synthesis of compound . An off-target screen was performed against an exten

• An alternative approach to improving pharmacokinetic profile

  2022-06-23

  

  An alternative approach to improving pharmacokinetic profile while retaining high GlyT1 potency was also pursued. Libraries were prepared in which potency enhancing piperidine C4 substituents were combined with clearance lowering truncated alkyl sulfonamides. The result was the discovery of (). Unl

• As GLO is the major

  2022-06-23

  

  As GLO1 is the major detoxification system of reactive dicarbonyls, it is plausible that differences in production and activity of the enzyme influences AGE production and the development and/or modulation of diabetic neuropathy. Glo1 exists as a copy number variant (CNV) in many inbred strains mice

• The lactam compounds including ceftriaxone CEF have shown to

  2022-06-23

  

  The β-lactam compounds, including ceftriaxone (CEF), have shown to attenuate drug-seeking in several drugs of abuse including methamphetamine [31], cocaine [32,33], nicotine [34] and morphine [35]. Moreover, in our laboratory, we have shown that CEF can reduce chronic alcohol drinking via upregulati

• br Dysregulation of glutamate transporter expression

  2022-06-23

  

  Dysregulation of glutamate transporter expression and function Aberrant glutamate transporter function and expression are associated with various neurological disorders. Therefore, understanding the underlying mechanisms of EAAT1/2 expression may provide therapeutic targets for treating neurolog

• Here we studied the effects of BZ

  2022-06-23

  

  Here we studied the effects of BZ flurazepam (FZ) at high doses in acute and chronic settings of tolerance and dependence in GluR-A−/− mice (Zamanillo et al., 1999). We used measurements in which the phenomenon of “learning while intoxicated” should play only a minor role in order to find out the si

• Nevertheless in the brain we found that trehalose phosphoryl

  2022-06-23

  

  Nevertheless, in the brain, we found that trehalose phosphorylates AMPK, which is a metabolic sensor. AMPK is known to be transiently activated in muscle by acute exercise [21,22]. Bayod et al. also reported that AMPK was significantly activated in both the cerebral cortex and hippocampus in exercis

• br Acknowledgements The authors are grateful for funding pro

  2022-06-23

  

  Acknowledgements The authors are grateful for funding provided by the Health Research Council of New Zealand. Introduction Glucose is the most important energy carrier of the brain. Glucose transporter type 1 (Glut1) is located at the blood–brain barrier and assures the energy-independent, fa

• Introduction Glucose dependent insulinotropic polypeptide GI

  2022-06-22

  

  Introduction Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted postprandially from enteroendocrine K cells in response to ingestion of either fat [1], protein [2], or carbohydrates [3]. GIP is primarily known for its glucose-dependent insulinotropic actions mediated via the G

• In this study an galactosidase gene GalA from

  2022-06-22

  

  In this study, an α-galactosidase gene, GalA, from a Aspergillus oryzae strain RIB40 [14] was artificially synthesized. To produce high levels of secretory expression in Pichia and facilitate its industrial application, we systematically investigated the gene dosages and the role of the ERSAs, namel

• In addition to Rabs several proteins have

  2022-06-22

  

  In addition to Rabs, several proteins have been shown to interact with Rabphilin3a, for instance the GluN2A subunit of the NMDA receptor, PSD-95 ([56,57] and references therein), Rabaptin-5, α-actinin [16] and SNAP-25 [21,23,41,61]. Only the latter has been reported to participate in the AR. Explori

• Accumulating evidence suggests an important role for

  2022-06-22

  

  Accumulating evidence suggests an important role for endothelin ETB receptors in renal homeostasis. ETB receptors promote vasodilation, natriuresis, and diuresis (Davenport and Maguire, 2011) and maintain renal perfusion via counterbalancing the effects of vasoconstrictors and regulation of water re

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