Month: November 2022

Sun, Ji-Fu published the artcileCaSR and calpain contribute to the ischemia reperfusion injury of spinal cord, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Neuroscience Letters (2017), 49-55, database is CAplus and MEDLINE.

Spinal cord ischemia reperfusion injury (SCIRI) can cause spinal cord dysfunction and even devastating paraplegia. Calcium-sensing receptor (CaSR) and calpain are two calcium related mols. which have been reported to be involved in the ischemia reperfusion injury of cardiomyocytes and the subsequent apoptosis. Here, we studied the expression of CaSR and calpain in spinal cord neurons and tissues, followed by the further investigation of the role of CaSR/calpain axis in the cellular apoptosis process during SCIRI. The results of in vitro and in vivo studies showed that the expression of CaSR and calpain in spinal cord neurons increased during SCIRI. Moreover, the CaSR agonist GdCl₃ and antagonist NPS-2390 enhanced or decreased the expression of CaSR and calpain resp. The expressions of CaSR and calpain were also consistent with the cellular apoptosis in spinal cord. Taken together, CaSR-calpain contributes to the SCIRI apoptosis, and CaSR antagonist might be a helpful drug for alleviating SCIRI.

Neuroscience Letters published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C6H5F4NO3S, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Pei, Gaofeng published the artcileCEBIT screening for inhibitors of the interaction between SARS-CoV-2 spike and ACE2, Category: quinoxaline, the publication is Fundamental Research (2022), 2(4), 562-569, database is CAplus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing COVID-19, is the most challenging pandemic of the modern era. It has resulted in over 5 million deaths worldwide. To quickly explore therapeutics for COVID-19, we utilized a previously-established system, namely CEBIT. We performed a high-throughput screening of FDA-approved drugs to inhibit the interaction between the receptor-binding domain (RBD) of SARS-CoV-2 spike protein and its obligate receptor ACE2. This interaction is essential for viral entry and therefore represents a promising therapeutic target. Based on the recruitment of interacting mols. into phase-separated condensates as a readout, we identified six pos. candidates from a library of 2572 compounds, most of which have been reported to inhibit the entry of SARS-CoV-2 into host cells. Our surface plasmon resonance (SPR) and mol. docking analyses revealed the possible mechanisms via which these compounds interfere with the interaction between RBD and ACE2. Hence, our results indicate that CEBIT is highly versatile for identifying drugs against SARS-CoV-2 entry, and targeting CoV-2 entry by small mol. drugs is a viable therapeutic option to treat COVID-19 in addition to commonly used monoclonal antibodies.

Fundamental Research published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Category: quinoxaline.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Zhu, Yiran published the artcileEffects of Cr(VI)-induced calcium-sensing receptor activation on DF-1 cell pyroptosis, Product Details of C19H21N3O, the publication is Ecotoxicology and Environmental Safety (2019), 257-264, database is CAplus and MEDLINE.

This study aims to investigate the effects of Cr(VI)-induced calcium-sensing receptor (CaSR) activation on DF-1 cell pyroptosis. Previous studies show that Cr(VI) could accumulate in the body of chickens and change Ca levels. Hence, a Ca-related pathway may be an important mechanism participating in some pathol. processes. Pyroptosis level, which is meditated by CaSR, increases under Cr(VI) accumulation. In the present study, pyroptosis was determined by flow cytometry to detect SYTOX blue and caspase-1 staining followed by morphol. observation. Interleukin (IL)-1β and IL-18 levels were detected by ELISA, while CaSR protein and [Ca²⁺]_i contents were detected by Western blot and fluorescence microplate spectrophotometry, resp. The results showed that Cr(VI) causes DF-1 cell pyroptosis in a time- and dose-dependent manner and that this effect is caspase-1 dependent. Further experiments indicated that pyroptosis could be induced by Cr(VI) and is accompanied by up-regulated [Ca²⁺]_i content. CaSR inhibition led to decreases in pyroptosis level. Some mechanisms may be involved in Cr(VI)-triggered CaSR activation and enhance DF-1 cell pyroptosis. Taken together, the results of this study support future investigations on Cr(VI)-induced pyroptosis in DF-1 cells.

Ecotoxicology and Environmental Safety published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C10H12O5, Product Details of C19H21N3O.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Rollema, Hans published the artcileEffect of co-administration of varenicline and antidepressants on extracellular monoamine concentrations in rat prefrontal cortex, HPLC of Formula: 375815-87-5, the publication is Neurochemistry International (2011), 58(1), 78-84, database is CAplus and MEDLINE.

Since a substantial proportion of smokers have comorbid mood disorders, the smoking cessation aid varenicline might occasionally be prescribed to patients who are simultaneously treated with antidepressants. Given that varenicline is a selective nicotinic acetylcholine receptor partial agonist and not a substrate or inhibitor of drug metabolizing enzymes, pharmacokinetic interactions with various classes of antidepressants are highly unlikely. It is, however, conceivable that varenicline may have a pharmacodynamic effect on antidepressant-evoked increases in central monoamine release. Interactions resulting in excessive transmitter release could cause adverse events such as serotonin syndrome, while attenuation of monoamine release could impact the clin. efficacy of antidepressants. To investigate this we examined whether varenicline administration modulates the effects of the selective serotonin reuptake inhibitor sertraline and the monoamine oxidase inhibitor clorgyline, given alone and combined, on extracellular concentrations of the monoamines serotonin, dopamine, and norepinephrine in rat brain by microdialysis. Given the important role attributed to cortical monoamine release in serotonin syndrome as well as antidepressant activity, the effects on extracellular monoamine concentrations were measured in the medial prefrontal cortex. Responses to maximally EDs of sertraline or clorgyline and of sertraline plus clorgyline were the same in the absence as in the presence of a relatively high dose of varenicline, which by itself had no significant effect on cortical monoamine release. This is consistent with the binding profile of varenicline that has insufficient affinity for receptors, enzymes, or transporters to inhibit or potentiate the pharmacol. effects of antidepressants. Since varenicline neither diminished nor potentiated sertraline- or clorgyline-induced increases in neurotransmitter levels, combining varenicline with serotonergic antidepressants is unlikely to cause excessive serotonin release or to attenuate antidepressant efficacy via effects on cortical serotonin, dopamine or norepinephrine release.

Neurochemistry International published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, HPLC of Formula: 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Slavov, Svetoslav H. published the artcileComputational identification of a phospholipidosis toxicophore using ¹³C and ¹⁵N NMR-distance based fingerprints, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Bioorganic & Medicinal Chemistry (2014), 22(23), 6706-6714, database is CAplus and MEDLINE.

Modified 3D-SDAR fingerprints combining ¹³C and ¹⁵N NMR chem. shifts augmented with inter-at. distances were used to model the potential of chems. to induce phospholipidosis (PLD). A curated dataset of 328 compounds (some of which were cationic amphiphilic drugs) was used to generate 3D-QSDAR models based on tessellations of the 3D-SDAR space with grids of different d. Composite PLS models averaging the aggregated predictions from 100 fully randomized individual models were generated. On each of the 100 runs, the activities of an external blind test set comprised of 294 proprietary chems. were predicted and averaged to provide composite estimates of their PLD-inducing potentials (PLD+ if PLD is observed, otherwise PLD-). The best performing 3D-QSDAR model utilized a grid with a d. of 8 ppm × 8 ppm in the C-C region, 8 ppm × 20 ppm in the C-N region and 20 ppm × 20 ppm in the N-N region. The classification predictive performance parameters of this model evaluated on the basis of the external test set were as follows: accuracy = 0.70, sensitivity = 0.73 and specificity = 0.66. A projection of the most frequently occurring bins on the standard coordinate space suggested a toxicophore composed of an aromatic ring with a centroid 3.5-7.5 Å distant from an amino-group. The presence of a second aromatic ring separated by a 4-5 Å spacer from the first ring and at a distance of between 5.5 Å and 7 Å from the amino-group was also associated with a PLD+ effect. These models provide comparable predictive performance to previously reported models for PLD with the added benefit of being based entirely on non-confidential, publicly available training data and with good predictive performance when tested in a rigorous, external validation exercise.

Bioorganic & Medicinal Chemistry published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C9H10N2O, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Mocking, Roel J. T. published the artcileEffects of short-term varenicline administration on cortisol in healthy, non-smoking adults: a randomized, double-blind, study, Related Products of quinoxaline, the publication is Psychopharmacology (Heidelberg, Germany) (2014), 231(1), 143-148, database is CAplus and MEDLINE.

Rationale: Varenicline is the most effective drug for smoking cessation, but its use decreased because of reports of depressogenic side effects. However, because smoking and smoking cessation on their own are associated with depression, it remains unclear whether reported depressogenic effects are attributable to varenicline, or to smoking, and/or smoking cessation themselves. Objectives: Previously, we observed no depressogenic effects of varenicline on a psychol. level. In the present study, we aimed at investigating potential depressogenic effects of the partial nicotinergic acetylcholine receptor agonist varenicline on a biol. level. A possible pathway would be an effect of varenicline on the hypothalamic-pituitary-adrenal (HPA) axis, considering the relation between the HPA axis and (1) the cholinergic system and (2) depression. Methods: In a randomized, double-blind design, we administered varenicline or placebo for 7 days (0.5 mg/day first 3 days, then 1 mg/day) to healthy never-smoking subjects, thereby eliminating bias by (previous) smoking status. We used repeated measures (before and after treatment) of the salivary free cortisol awakening response to measure HPA axis activity and flexibility. Results: Salivary cortisol data of 34 subjects were included in the anal. Results showed no effect of varenicline on height (F_1,32 = 0.405; P = 0.529) or shape (F_2,31 = 0.110; P = 0.164) of the cortisol awakening response. Conclusions: Results do not suggest depressogenic effects of varenicline on the HPA axis. Although this does not preclude other biol. depressogenic effects of varenicline, it seems that concerns about effects of varenicline on the HPA axis should not limit its potential to treat nicotine and related addictions.

Psychopharmacology (Heidelberg, Germany) published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Related Products of quinoxaline.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Carson, Kristin V. published the artcileSmoking cessation interventions for lung cancer patients, Computed Properties of 375815-87-5, the publication is Lung Cancer Management (2013), 2(1), 61-74, database is CAplus.

A review. SUMMARY Worldwide, lung cancer contributes to over 1.4 million deaths per yr. Smoking cessation is strongly recommended in clin. practice guidelines for lung cancer management, yet evidence suggests a translational gap between evidence and practice. There are significant health benefits following smoking cessation even after a short period of time. Long-term implications for lung cancer patients include improvements in quality of life, reductions in postoperative complications and reductions in 12-mo mortality. Evidence suggests that combining pharmacotherapy, in particular varenicline tartrate (varenicline), with cognitive and behavioral interventions offers the best opportunity for successful long-term abstinence. This review summarizes the latest evidence for smoking cessation interventions in lung cancer patients, identifies gaps in current clin. practice and highlights priority areas for future research.

Lung Cancer Management published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Computed Properties of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Yanamala, Naveena published the artcilePreferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors, Category: quinoxaline, the publication is BMC Bioinformatics (2008), No pp. given, database is CAplus and MEDLINE.

Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiol. and pathol. processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, the authors propose the hypothesis that pos. and neg. modulators will differentially stabilize the active and inactive conformations of the receptors, resp. To test this hypothesis, the authors have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is exptl. known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. The authors find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%), the neg. modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%), the pos. modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86%) and 8/9 (89%) for ArgusLab and 10/14 (71%) and 7/9 (78%) for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by photochem. isomerization of the retinal ligand – despite the extensive differences in sequences between mGluRs and rhodopsin.

BMC Bioinformatics published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C38H74Cl2N2O4, Category: quinoxaline.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Hong, L. Elliot published the artcileEffects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder, Application In Synthesis of 375815-87-5, the publication is Archives of General Psychiatry (2011), 68(12), 1195-1206, database is CAplus and MEDLINE.

The administration of nicotine transiently improves many neurobiol. and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder. Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans. A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder was conducted to examine the effects of varenicline on biomarkers at 2 wk (short-term treatment) and 8 wk (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects. Participants included a total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Main outcome measures were prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention. Results: A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P=.006), (2) reduced startle reactivity (P=.02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P=.03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners’ Continuous Performance Test. Clin., there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose). Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biol. deficits. Trial Registration: clinicaltrials.gov Identifier: NCT00492349.

Archives of General Psychiatry published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Application In Synthesis of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Lu, Yuting published the artcileImpurity profiling of varenicline tartrate by LC-QTOF mass spectrometric techniques during drug development, Product Details of C17H19N3O6, the publication is Journal of Pharmaceutical and Biomedical Analysis (2018), 306-313, database is CAplus and MEDLINE.

HPLC-QTOF-MS method was developed for the separation and characterization of related substances in varenicline tartrate drug material. The separation used InertSustain C18 column (4.6 × 150 mm, 5 μm) with liner gradient elution using 0.05% trifluoroacetic acid as mobile phase A and acetonitrile as mobile phase B. The degradation studies were conducted under the ICH prescribed stress conditions. Varenicline tartrate was unstable to alk., oxidative, thermal and photolytic stresses, but relatively stable under acid stress condition. Thirteen related substances were found in varenicline tartrate and its stressed samples. Their structures were identified mainly through pos. ESI high resolution QTOF mass spectrometric anal. of the parent and product ion accurate masses and the calculated elemental compositions Among the 13 substances, 7 were process-related and 6 were degradation products, and two of them were further verified by chem. synthesis and NMR spectroscopic determination Their formation mechanisms are discussed, and the key steps in the manufacturing processes are determined to provide varenicline tartrate with high purity.

Journal of Pharmaceutical and Biomedical Analysis published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Product Details of C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider