Month: October 2022

Wang, Qi; Li, Ying; Li, Kun-Wei; Zhou, Chang-Zheng published the artcile< Sophoridine: A review of its pharmacology, pharmacokinetics and toxicity>, Synthetic Route of 6882-68-4, the main research area is Review sophoridine pharmacol pharmacokinetics toxicity; Pharmacokinetics; Pharmacology; Sophoridine; Toxicology.

A review. Sophoridine is a bioactive alkaloid found in many Chinese herbs, such as Sophora alopecuroides l, Euchresta japonica Benth and Sophora moocrorftinan. Sophoridine hydrochloride injection has been approved as an anticancer drug in China. This aims to provide a comprehensive summary on the pharmacol., mol. mechanism, pharmacokinetic and toxicity studies of sophoridine. PubMed, Web of Science and China National Knowledge Infrastructure were used for a systematic search with the keywords including “”sophoridine””, “”pharmacol.””, “”pharmacokinetics””, and “”toxicity””. Emerging evidence suggests that sophoridine exhibits a broad spectrum of pharmacol. activities including antitumor, anti-inflammatory, antiviral, myocardialprotective and hepatoprotective activities. These pharmacol. properties lay foundation for using the plants containing sophoridine for the treatment of numerous diseases, such as cancer, colitis, injury of lungs, ischemia myocardial,etc. The mechanisms involved in the pharmacol. actions of sophoridine are regulation of NF-κB, TLR4/IRF3, JNK/ERK, Akt/mTOR signaling pathways, down-regulating the expression of HMG3B, bcl-2, MMP-2, MMP-9, TNF-α, IL-1β IL-6 and other cytokines or kinases. However, an increasing number of published reports indicated that sophoridine has serious adverse effects. The primary toxic effects are neurotoxicity and acute toxicity, which are of wide concern in worldwide. Moreover, sophoridine is reported to distribute in kidney, liver, uterus, lung and other organs. It undergoes glucuronidation and excreted in urine. Future studies should elucidate the detailed in vivo metabolism studies on sophoridine. The effect of substituent functional groups on sophoridine on metabolism, the enzymes involved in the metabolism and the chem. of metabolites also should be studied. Either structural modification of sophoridine or its combined with other drugs may play a pivotal role to enhance its pharmacol. activities and reduce its toxicity.

Phytomedicine published new progress about Animal gene, Bcl-2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Synthetic Route of 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Miller, William P.; Mihailescu, Maria L.; Yang, Chen; Barber, Alistair J.; Kimball, Scot R.; Jefferson, Leonard S.; Dennis, Michael D. published the artcile< The translational repressor 4E-BP1 contributes to diabetes-induced visual dysfunction>, Quality Control of 1223001-51-1, the main research area is diabetes visual dysfunction 4EBP1.

PURPOSE: The translational repressor 4E-BP1 interacts with the mRNA cap-binding protein eIF4E and thereby promotes cap-independent translation of mRNAs encoding proteins that contribute to diabetic retinopathy. Interaction of 4E-BP1 with eIF4E is enhanced in the retina of diabetic rodents, at least in part, as a result of elevated 4E-BP1 protein expression. In the present study, we examined the role of 4E-BP1 in diabetes-induced visual dysfunction, as well as the mechanism whereby hyperglycemia promotes 4E-BP1 expression. METHODS: Nondiabetic and diabetic wild-type and 4E-BP1/2 knockout mice were evaluated for visual function using a virtual optomotor test (Optomotry). Retinas were harvested from nondiabetic and type 1 diabetic mice and analyzed for protein abundance and posttranslational modifications. Similar analyses were performed on cells in culture exposed to hyperglycemic conditions or an O-GlcNAcase inhibitor (Thiamet G [TMG]). RESULTS: Diabetes-induced visual dysfunction was delayed in mice deficient of 4E-BP1/2 as compared to controls. 4E-BP1 protein expression was enhanced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in retinal cells in culture. A similar elevation in 4E-BP1 expression was observed with TMG. The rate of 4E-BP1 degradation was significantly prolonged by either hyperglycemic conditions or TMG. A PEST motif in the C-terminus of 4E-BP1 regulated polyubiquitination, turnover, and binding of an E3 ubiquitin ligase complex containing CUL3. CONCLUSIONS: The findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif.

Investigative Ophthalmology & Visual Science published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Banerjee, Dipanjan; Sinha, Archana; Saikia, Sudeshna; Gogoi, Bhaskarjyoti; Rathore, Arvind K.; Das, Anindhya Sundar; Pal, Durba; Buragohain, Alak K.; Dasgupta, Suman published the artcile< Inflammation-induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation>, Formula: C24H15F3N4O, the main research area is inflammation mTORC1 2 Akt signal transduction macrophage foam cell; Akt phosphorylation; Inflammation; Macrophage foam cell; TLR4 signaling; mTORC2.

The transformation of macrophages into lipid-loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying mol. mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression, and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation-induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation.

Biochimie published new progress about Atherosclerosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Formula: C24H15F3N4O.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Zhao, Wu-li; Xing, Yan; Ye, Cheng; Qiu, Yu-han; Li, Yi; Liu, Xiu-jun; Wang, Meng-yan; Bi, Chong-wen; Song, Dan-qing; Shao, Rong-guang published the artcile< The novel sophoridine derivate IMB-HDC induced lessened phosphorylation of STAT5a at 694 and 780 and promoted DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation>, Computed Properties of 6882-68-4, the main research area is cancer cell apoptosis sophoridine derivate STAT5a DNA breakage; DNA breakage; STAT5a; anticancer; nuclear location; shuttle.

Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. Meanwhile, IMB-HDC that induced the diminished expression of STAT5a target gene contributes to proliferation and leads to apoptosis. More importantly, we give the first evidence that promoting the effect of Tyr694 phosphorylation on nuclear location and subsequent STAT5a target gene transcription depends on Ser780 increased or unchanged phosphorylation and was not correlated with Ser726 phosphorylation.

Acta Pharmacologica Sinica published new progress about Animal gene, Bcl-2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Computed Properties of 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Vinoth, M.; Natarajan, B.; Sundaram, C. Shanmuga published the artcile< Characterization and evaluation ethyl acetate extract of melochia corchorifolia leaf-anticancer antibiological and molecular docking studies on breast cancer estrogen receptor>, Reference of 6882-68-4, the main research area is Melochia leaf extract anticancer antibiol breast cancer estrogen receptor.

The present work focused on Phytochem. screening, characterization, anticancer activity and antibiol. activity of Et acetate extract of Melochia corchorifolia leaves followed by mol. docking studies have been carried out. The plant leaves have been collected, weighed, and extracted with the soxhlet apparatus by using Et acetate solvent and then extracted are subjected to phytochem. screening. Antibiol. activity of plant leaves Et acetate extract has been tested against six bacterial and two fungal strains using agar well diffusion methodol. The characterization of phytoconstituents compounds has been carried out using various spectroscopy method such as GC-MS (Gas chromatog. Mass spectroscopy), UV-visible and Fourier-transform IR. Auto dock tool (4.2.0) is used for mol. docking studies. The phytochem. anal. of Melochia corchorifolia Et acetate leaves, reveals the existence of carbohydrates, glycosides, triterpenes flavonoids and alkaloids. Antimicrobial activity is effective against gram-pos. bacterial strains namely Staphylococcus aureus (17 mm), Bacillus subtilis (16 mm), the gram-neg. bacterial strains namely Salmonella typhi (15 mm) and E. coli (14 mm). Moreover, the extract is also found to be effective against Aspergillus Niger (18 mm) fungal species. The GC-MS and FT-IR anal. show bioactive compounds and their functional groups. UV-VIS anal. results reveal that the presence of phytoconstituents derivatives in the range between 206-350 nm. The cytotoxicity activity for the MCF-7 cell line shows that the drug efficacy IC50 value is 148.836 (μg/mL). Further, the predicted bioactive compounds are docked with the cancer estrogen protein receptor (PDB ID: 3s7s) with ligand martidin-15 one shows the highest binding affinity. The study reveals the potential of Melochia corchorifolia leaves Et acetate extract showed antibiol. and anticancer activity.

Indian Journal of Chemical Technology published new progress about Affinity (Binding). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Reference of 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Blazejewski, Sara M.; Bennison, Sarah A.; Liu, Xiaonan; Toyo-oka, Kazuhito published the artcile< High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is high throughput screening aurora nuak kinase inhibitor neurite initiation.

Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation-a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative disease, and seizures. Investigating the mechanisms underlying neurite formation will allow for identification of potential therapeutics. We used a kinase inhibitor library to screen 493 kinase inhibitors and observed that 45% impacted neuritogenesis in Neuro2a (N-2a) cells. Based on the screening, we further investigated the roles of Aurora kinases A, B, and C and Nuak kinases 1 and 2. The roles of Aurora and Nuak kinases have not been thoroughly studied in the nervous system. Inhibition or overexpression of Aurora and Nuak kinases in primary cortical neurons resulted in various neuromorphol. defects, with Aurora A regulating neurite initiation, Aurora B and C regulating neurite initiation and elongation, all Aurora kinases regulating arborization, and all Nuak kinases regulating neurite initiation and elongation and arborization. Our high-throughput screening and anal. of Aurora and Nuak kinases revealed their functions and may contribute to the identification of therapeutics.

Scientific Reportspublished new progress about Aurora kinase inhibitors. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Xu, Fei; Li, Xin; Yan, Lili; Yuan, Na; Fang, Yixuan; Cao, Yan; Xu, Li; Zhang, Xiaoying; Xu, Lan; Ge, Chaorong; An, Ni; Jiang, Gaoyue; Xie, Jialing; Zhang, Han; Jiang, Jiayi; Li, Xiaotian; Yao, Lei; Zhang, Suping; Zhou, Daohong; Wang, Jianrong published the artcile< Autophagy promotes the repair of radiation-induced DNA damage in bone marrow hematopoietic cells via enhanced STAT3 signaling>, Electric Literature of 1223001-51-1, the main research area is gamma radiation autophagy DNA damage BM hematopoietic cell.

Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the mol. mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7. The autophagic regulation of STAT3 activation is likely mediated by induction of KAP1 degradation, because we showed that KAP1 directly interacted with STAT3 in the cytoplasm and knockdown of KAP1 increased the phosphorylation and nuclear translocation of STAT3. Subsequently, activated STAT3 transcriptionally upregulated the expression of BRCA1, which increased the ability of BM-MNCs to repair radiation-induced DNA damage. This novel finding that activation of autophagy can promote DNA damage repair in BM-MNCs via the ATG-KAP1-STAT3-BRCA1 pathway suggests that autophagy plays an important role in maintaining genomic integrity of BM-MNCs and its activation may confer protection of BM-MNCs against radiationinduced genotoxic stress.

Radiation Researchpublished new progress about Autophagy. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Electric Literature of 1223001-51-1.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Ma, Baowei; Athari, Seyyed Shamsadin; Mehrabi Nasab, Entezar; Zhao, Limin published the artcile< PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma>, Computed Properties of 1223001-51-1, the main research area is allergic asthma PI3K AKT mTOR TLR4 MyD88 NFkB; Th; asthma; inflammation; signaling; target therapy; treatment.

Asthma is an inflammatory airway disease wherein bronchoconstriction, airway inflammation, and airway obstruction during asthma attacks are the main problems. It is recognized that imbalance of Th1/Th2 and Th17/Treg is a critical factor in asthma pathogenesis. Manipulation of these with signaling mols. such as mTOR, PI3K, Akt, and MyD88 can control asthma. Mouse model of allergic asthma was produced and treated with ketamine, metformin, metformin and ketamine, triciribine, LY294002, and torin2. MCh challenge test, BALfs Eos Count, the IL-4, 5, INF-γ, eicosanoid, total IgE levels were determined The MUC5a, Foxp3, RORγt, PI3K, mTOR, Akt, PU.1, and MyD88 gene expressions and histopathol. study were done. Asthma groups that were treated with all six components had reduced Penh value, total IgE, IL-4 and IL-5 levels, MUC5a, RORγt, MyD88 and mTOR expression, goblet cell hyperplasia, and mucus hyper-secretion. The eosinophil percentage and Cys-LT level were decreased by metformin and ketamine, triciribine, LY294002, and torin2. The level of IFN-γ was increased in triciribine, LY294002, and torin2. Metformin, metformin and ketamine, triciribine, LY294002, and torin2 reduced Akt and PI3K expression, peribronchial and perivascular inflammation, and increased expression of Foxp3. Torin2 had an effect on PU.1 expression. Inhibition of PI3K/AKT/mTOR and TLR4/MyD88/NF-κB signaling with targeted mols. can attenuate asthma pathol. and play an important role in airways protection.

Inflammationpublished new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (RORgt). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Computed Properties of 1223001-51-1.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Zhu, Naiqiang; Hou, Jingyi published the artcile< Molecular mechanism of the anti-inflammatory effects of Sophorae Flavescentis Aiton identified by network pharmacology>, Computed Properties of 6882-68-4, the main research area is Sophora flavescens antiinflammatory effect mol mechanism network pharmacol.

Inflammation, a protective response against infection and injury, involves a variety of biol. processes. Sophorae Flavescentis (Kushen) is a promising Traditional Chinese Medicine (TCM) for treating inflammation, but the pharmacol. mechanism of Kushen’s anti-inflammatory effect has not been fully elucidated. The bioactive compounds, predicted targets, and inflammation-related targets of Kushen were obtained from open source databases. The ”Component-Target” network and protein-protein interaction (PPI) network were constructed, and hub genes were screened out by topol. anal. Gene ontol. (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on genes in the PPI network. Furthermore, nitric oxide (NO) production anal., RT-PCR, and western blot were performed to detect the mRNA and protein expression of hub genes in LPS-induced RAW264.7 cells. An immunofluorescence assay found that NF-κB p65 is translocated. A total of 24 bioactive compounds, 465 predicted targets, and 433 inflammation-related targets were identified and used to construct ”Component-Targets” and PPI networks. Then, the five hub genes with the highest values-IL-6, IL-1β, VEGFA, TNF-α, and PTGS2 (COX-2)- were screened out. Enrichment anal. results suggested mainly involved in the NF-κB signaling pathway. Moreover, experiments were performed to verify the predicted results. Kushen may mediate inflammation mainly through the IL-6, IL-1β, VEGFA, TNF-α, and PTGS2 (COX-2), and the NF-κB signaling pathways. This finding will provide clin. guidance for further research on the use of Kushen to treat inflammation.

Scientific Reportspublished new progress about Anti-inflammatory agents. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Computed Properties of 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Ponsford, Amy H.; Ryan, Thomas A.; Raimondi, Andrea; Cocucci, Emanuele; Wycislo, Susanne A.; Frohlich, Florian; Swan, Laura E.; Stagi, Massimiliano published the artcile< Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor>, Related Products of 1223001-51-1, the main research area is chloroquine fluorescence microscopy lysosome MTOR protein pH Vtype ATPase; Chloroquine; MTOR protein; V-type ATPase; fluorescence microscopy; lysosomes; pH.

Disorders of lysosomal physiol. have increasingly been found to underlie the pathol. of a rapidly growing cast of neurodevelopmental disorders and sporadic diseases of aging. One cardinal aspect of lysosomal (dys)function is lysosomal acidification in which defects trigger lysosomal stress signaling and defects in proteolytic capacity. We have developed a genetically encoded ratiometric probe to measure lysosomal pH coupled with a purification tag to efficiently purify lysosomes for both proteomic and in vitro evaluation of their function. Using our probe, we showed that lysosomal pH is remarkably stable over a period of days in a variety of cell types. Addnl., this probe can be used to determine that lysosomal stress signaling via TFEB is uncoupled from gross changes in lysosomal pH. Finally, we demonstrated that while overexpression of ARL8B GTPase causes striking alkalinization of peripheral lysosomes in HEK293 T cells, peripheral lysosomes per se are no less acidic than juxtanuclear lysosomes in our cell lines.

Autophagypublished new progress about Acidification. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Related Products of 1223001-51-1.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem