Heterocyclic Building Blocks-Naphthyridine

Al-Ali, Hassan; Ding, Ying; Slepak, Tatiana; Wu, Wei; Sun, Yan; Martinez, Yania; Xu, Xiao-Ming; Lemmon, Vance P.; Bixby, John L. published the artcile< The mTOR substrate S6 kinase 1 (S6K1) is a negative regulator of axon regeneration and a potential drug target for central nervous System Injury>, Formula: C24H15F3N4O, the main research area is central nervous system injury axon regeneration mTOR SK; S6K; axon regeneration; drug discovery; drug target; kinase; spinal cord injury.

The mammalian target of rapamycin (mTOR) pos. regulates axon growth in the mammalian central nervous system (CNS). Although axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a neg. regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR’s pos. effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by twofold to threefold. Biochem. anal. revealed that an mTOR-dependent induction of PI3K signaling is involved in mediating this effect of S6K1 inhibition. Importantly, treating female mice in vivo with PF-4708671, a selective S6K1 inhibitor, stimulated corticospinal tract regeneration across a dorsal spinal hemisection between the cervical 5 and 6 cord segments (C5/C6), increasing axon counts for at least 3 mm beyond the injury site at 8 wk after injury. Concomitantly, treatment with PF-4708671 produced significant locomotor recovery. Pharmacol. targeting of S6K1 may therefore constitute an attractive strategy for promoting axon regeneration following CNS injury, especially given that S6K1 inhibitors are being assessed in clin. trials for nononcol. indications.

Journal of Neuroscience published new progress about Central nervous system injury. 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

Ye, Xian-wen; Deng, Ya-ling; Zhang, Xia; Liu, Min-min; Liu, Ying; Xie, Ya-ting; Wan, Quan; Huang, Min; Zhang, Tao; Xi, Jia-he; Zhang, Jin-lian published the artcile< Study on the mechanism of treating COVID-19 with Shenqi Wan based on network pharmacology>, Application In Synthesis of 6882-68-4, the main research area is Shenqi Wan network pharmacol COVID treatment; Shenqi Wan; mechanism; molecular docking; network pharmacology; novel coronavirus pneumonia.

Through the method of network pharmacol., the active components and targets of Shenqi Wan (SQW) were excavated, the relationship with novel Coronavirus pneumonia (COVID-19) was discussed, and the possible mechanism of SQW in the treatment of COVID-19 was revealed from the aspects of multicomponents, multitargets, and multipathways. Firstly, the active components of SQW were screened from traditional Chinese medicine systems pharmacol. database and anal. platform and the 2020 edition of Chinese Pharmacopeia, and the related targets of the components were obtained. Then the disease targets related to COVID-19 were screened from GeneCards and Online Mendelian Inheritance in Man. Venny was used to map the relationship between component-target and disease-target, and String was used to analyze the interaction of common targets. The network was constructed and analyzed by Cytoscape, the function of Gene ontol. (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) genes was enriched by Metascape, and the mol. docking was verified by CB-Dock. Finally, 45 active components of SQW were obtained, and 72 potential targets were related to COVID-19, angiotensin-converting enzyme 2 (ACE2), interleukin (IL)-6, nitric oxide synthase (NOS3) and, C-reactive protein (CRP),may be the key targets. GO enrichment of 1715 projects, such as lipopolysaccharide stress response, active oxygen metabolism, pos. regulation of cell migration, and other GO enrichment. About 136 KEGG pathways, tumor necrosis factor signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor 1-α signaling pathway were obtained. Mol. docking showed that kaempferol, quercetin, luteolin, astragaloside, calyx isoflavone glucoside, matrine, and other COVID-19-related targets such as ACE2, chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), prostaglandin-endoperoxide synthase 2 (PTGS2) have good binding ability. According to the above results, it is suggested that SQW may play a role in the treatment of COVID-19 by directly or indirectly combining kaempferol, quercetin, and luteolin with ACE2, 3CLpro, PLpro, and PTGS2 to regulate multiple biol. functions and signaling pathways.

Drug Development and Industrial Pharmacy published new progress about Adipose tissue. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Application In Synthesis of 6882-68-4.

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

Liang, Jinping; Liu, Juntong; Tang, Yezhen; Peng, Qian; Zhang, Ling; Ma, Xiaoxia; Xu, Nan; Wei, Jun; Han, Huaiqin published the artcile< Sophoridine inhibits endotoxin-induced acute lung injury by enhancing autophagy of macrophage and reducing inflammation>, Formula: C15H24N2O, the main research area is sophoridine macrophage autophagy inflammation acute lung injury; acute lung injury; autophagy; inflammation; sophoridine.

Acute lung injury (ALI) is characterized by uncontrolled inflammation, which can lead to respiratory distress syndrome and cause patient death. In this study, we sought to determine the role of sophoridine, a compound purified from sophora, in ALI. A mouse model of ALI was established by treating mice with LPS through nonexposed tracheal instillation. After LPS-induced mice were treated with sophoridine, LPS-induced alveolar wall thickening, alveolar interstitial inflammatory exudation and thickening, and the degree of pulmonary edema were found to be inhibited. Macrophages play an important role in inflammation, and in vitro experiments have demonstrated that sophoridine reduces the LPS-induced expression of inflammatory factors by macrophages, suggesting that sophoridine may inhibit lung inflammation in LPS-treated mice through reduces the secretion of inflammatory factors. Further, treatment with sophoridine up-regulated autophagy in macrophage cells in vitro and mouse lung tissues in vivo. LPS can bind to TLRs and activate the MyD88/NF-κB pathways, leading to increased inflammation in the pathogenesis of ALI. Our findings revealed that sophoridine down-regulated the expression of TLR4/MyD88/NF-κB and mTOR mRNA and protein in mouse pulmonary tissue. Collectively, these findings indicate that sophoridine may inhibit LPS-induced ALI by enhancing autophagy of macrophages and reducing inflammation.

Journal of Leukocyte Biology published new progress about Acute pulmonary injury. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Formula: C15H24N2O.

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

Li, Yanchu; Chen, Lu; Pu, Rong; Zhou, Lu; Zhou, Xufeng; Li, Xianyong published the artcile< Effects of a Matrine- and Sophoridine-Containing Herbal Compound Medicine (AH-05) on Liver Cancer>, Computed Properties of 6882-68-4, the main research area is liver cancer matrine sophoridine AH05.

Herbal medicine can present an alternative way of treating liver cancer. Here, we explored a matrine- and sophoridine-containing herbal compound medicine (AH-05) extracted from Adenophora capillaris, Sophora flavescens, Astragalus, and other plants. H22 and HepG2 cell models, as well as an H22 xenograft model, were established. Cell proliferation and apoptosis were measured in vitro, and tumor volume and weight were observed in vivo. The activation of AKT/mTOR and nuclear factor-κB (NF-κB) pathways in tumor cells and the polarization of CD4/CD8 T cells in the spleen were tested. To assess safety, hematol. toxicity and pathol. of the liver, kidney, spleen, and intestine were evaluated. AH-05 inhibited cell viability in a dose- and time-dependent manner. In vivo, tumor volume and weight were reduced, and the activation of NF-κB p50, NF-κB p65, AKT, p-AKT Ser473, and mTOR was suppressed. In addition, AH-05 promoted CD4+ T cell polarization in the spleen. With regard to safety, slight intestinal mucosa edema was observed, but no severe pathol. or hematol. toxicity was detected. AH-05 exhibited its therapeutic effects against liver cancer by regulating the AKT/mTOR and NF-κB signaling pathways, and the immune environment, by promoting CD4+ T cell polarization in the spleen. Thus, AH-05 represents a potential supplementary herbal compound medicine for liver cancer.

Natural Product Communications published new progress about Apoptosis. 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

Vogel, K. R.; Ainslie, G. R.; Jansen, E. E. W.; Salomons, G. S.; Gibson, K. M. published the artcile< Therapeutic relevance of mTOR inhibition in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is torin mTOR succinate semialdehyde dehydrogenase deficiency GABA oxidataive stress; GABA; Oxidative stress; Succinic semialdehyde dehydrogenase deficiency; Torin 1; Torin 2; mTOR.

Aldehyde dehydrogenase 5a1-deficient (aldh5a1-/-) mice, the murine orthologue of human succinic semialdehyde dehydrogenase deficiency (SSADHD), manifest increased GABA (4-aminobutyric acid) that disrupts autophagy, increases mitochondria number, and induces oxidative stress, all mitigated with the mTOR (mechanistic target of rapamycin) inhibitor rapamycin [1]. Because GABA regulates mTOR, we tested the hypothesis that aldh5a1-/- mice would show altered levels of mRNA for genes associated with mTOR signaling and oxidative stress that could be mitigated by inhibiting mTOR. We observed that multiple metabolites associated with GABA metabolism (γ-hydroxybutyrate, succinic semialdehyde, D-2-hydroxyglutarate, 4,5-dihydrohexanoate) and oxidative stress were significantly increased in multiple tissues derived from aldh5a1-/- mice. These metabolic perturbations were associated with decreased levels of reduced glutathione (GSH) in brain and liver of aldh5a1-/- mice, as well as increased levels of adducts of the lipid peroxidation byproduct, 4-hydroxy-2-nonenal (4-HNE). Decreased liver mRNA levels for multiple genes associated with mTOR signaling and oxidative stress parameters were detected in aldh5a1-/- mice, and several were significantly improved with the administration of mTOR inhibitors (Torin 1/Torin 2). Western blot anal. of selected proteins corresponding to oxidative stress transcripts (glutathione transferase, superoxide dismutase, peroxiredoxin 1) confirmed gene expression findings. Our data provide addnl. preclin. evidence for the potential therapeutic efficacy of mTOR inhibitors in SSADHD.

Biochimica et Biophysica Acta, Molecular Basis of Disease published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Name: 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

Dong, Yaqian; Jia, Guoxiang; Hu, Jingwen; Liu, Hui; Wu, Tingting; Yang, Shenshen; Li, Yubo; Cai, Ting published the artcile< Determination of alkaloids and flavonoids in Sophora flavescens by UHPLC-Q-TOF/MS>, Reference of 6882-68-4, the main research area is Sophora flavescens alkaloid flavonoid determination UHPLC Q TOF MS.

This study is based on UHPLC-Q-TOF/MS and fragment ions to achieve classification and identification of alkaloids and flavonoids in Sophora flavescens. By reviewing the available and relevant literature, the mass fragmentation rules of alkaloids and flavonoids were summarized. 0.1% formic acid water (A) and acetonitrile (B) were used as mobile phases. 37 chem. constituents were identified, including 13 alkaloids and 24 flavonoids. This research method offers a complete strategy based on the fragmentation information of characteristic fragment ions and neutral loss obtained by MS/MS to characterize the chem. composition of Sophora flavescens.

Journal of Analytical Methods in Chemistry published new progress about Alkaloids Role: ANT (Analyte), ANST (Analytical Study). 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

Cobbold, Simon A.; Chua, Hwa H.; Nijaga, Brunda; Creek, Darren J.; Ralph, Stuart A.; McConville, Malcolm J. published the artcile< Metabolic dysregulation induced in Plasmodium falciparum by dihydroartemisinin and other front-line antimalarial drugs>, Reference of 1223001-51-1, the main research area is Plasmodium dihydroartemisinin antimalarial metabolic dysregulation; Plasmodium; antimalarial; artemisinin; atovaquone; chloroquine; drug screening; malaria; metabolite; metabolomics; torin.

Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clin. antimalarial drugs and inhibitors on Plasmodium falciparum asexual blood stages. Drug-induced changes in metabolite levels in P. falciparum-infected erythrocytes were monitored over time using gas chromatog.-MS and liquid chromatog.-MS and changes in specific metabolic fluxes confirmed by nonstationary [13C]-glucose labeling. Dihydroartemisinin (DHA) was found to disrupt Hb catabolism within 1 h of exposure, resulting in a transient decrease in Hb-derived peptides. Unexpectedly, it also disrupted pyrimidine biosynthesis, resulting in increased [13C]-glucose flux toward malate production, potentially explaining the susceptibility of P. falciparum to DHA during early blood-stage development. Unique metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and methylene blue. We also show that this approach can be used to identify the mode of action of novel antimalarials, such as the compound Torin 2, which inhibits Hb catabolism.

Journal of Infectious Diseases published new progress about Antimalarials. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Reference 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>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, 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.

Inflammation published 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, Name: 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

Zhang, Zhenfeng; Peng, Huixin; Wang, Xiaojie; Yin, Xia; Ma, Pengfei; Jing, Ying; Cai, Mei-Chun; Liu, Jin; Zhang, Meiying; Zhang, Shengzhe; Shi, Kaixuan; Gao, Wei-Qiang; Di, Wen; Zhuang, Guanglei published the artcile< Preclinical Efficacy and Molecular Mechanism of Targeting CDK7-Dependent Transcriptional Addiction in Ovarian Cancer>, COA of Formula: C24H15F3N4O, the main research area is ovarian cancer cell transcriptional addiction CDK7 THZ1 efficacy.

Ovarian cancer remains a significant cause of gynecol. cancer mortality, and novel therapeutic strategies are urgently needed in clinic as new treatment options. We previously showed that BET bromodomain inhibitors displayed promising efficacy for the treatment of epithelial ovarian cancer by downregulating pivot transcription factors. However, the potential antitumor activities and mol. mechanisms of other epigenetic or transcriptional therapies have not been systematically determined Here, by performing an unbiased high-throughput drug screen to identify candidate compounds with antineoplastic effects, we identified THZ1, a recently developed covalent CDK7 inhibitor, as a new transcription-targeting compound that exerted broad cytotoxicity against ovarian tumors. Mechanistically, CDK7 represented a previously unappreciated actionable vulnerability in ovarian cancer, and CDK7 inhibition led to a pronounced dysregulation of gene transcription, with a preferential repression of E2F-regulated genes and transcripts associated with super-enhancers. Our findings revealed the mol. underpinnings of THZ1 potency and established pharmaceutically targeting transcriptional addiction as a promising therapeutic strategy in aggressive ovarian cancer. Mol Cancer Ther; 16(9); 1739-50. ©2017 AACR.

Molecular Cancer Therapeutics published new progress about Antitumor agents. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, COA of Formula: C24H15F3N4O.

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

Almstedt, Elin; Elgendy, Ramy; Hekmati, Neda; Rosen, Emil; Waern, Caroline; Olsen, Thale Kristin; Dyberg, Cecilia; Doroszko, Milena; Larsson, Ida; Sundstroem, Anders; Arsenian Henriksson, Marie; Paahlman, Sven; Bexell, Daniel; Vanlandewijck, Michael; Kogner, Per; Joernsten, Rebecka; Krona, Cecilia; Nelander, Sven published the artcile< Integrative discovery of treatments for high-risk neuroblastoma>, Product Details of C24H15F3N4O, the main research area is neuroblastoma CNR2 MAPK8 Target Translator algorithm.

Despite advances in the mol. exploration of paediatric cancers, approx. 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with exptl. evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumor biobanks, pharmacol. databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.

Nature Communications published new progress about Apoptosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Product Details of C24H15F3N4O.

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