Month: October 2022

Harari, Emanuel; Guo, Liang; Smith, Samantha L.; Paek, Ka Hyun; Fernandez, Raquel; Sakamoto, Atsushi; Mori, Hiroyoshi; Kutyna, Matthew D.; Habib, Anwer; Torii, Sho; Cornelissen, Anne; Jinnouchi, Hiroyuki; Gupta, Anuj; Kolodgie, Frank D.; Virmani, Renu; Finn, Aloke V. published the artcile< Direct Targeting of the mTOR (Mammalian Target of Rapamycin) Kinase Improves Endothelial Permeability in Drug-Eluting Stents-Brief Report>, Related Products of 1223001-51-1, the main research area is atherosclerosis mTOR kinase endothelial permeability drug eluting stent; animals; atherosclerosis; drug-eluting stents; endothelium; rabbits; stents.

We recently showed that canonical mTOR inhibitors bind FKBP12.6, displace it from calcium release channels, resulting in activation of PKCa (protein kinase Ca) and dissociation of p-120-catenin (p120) from vascular endothelial cadherin; promoting endothelial barrier dysfunction. However, the relevance of these findings to drug-eluting stents remains unknown. Newer generation direct mTOR kinase inhibitors do not bind FKBP12.6 and offer the potential of improving endothelial barrier function while maintaining antirestenotic efficacy, but their actual effects are unknown. We examined the effects of 2 different pharmacol. targeting strategies-canonical mTOR inhibitor everolimus and mTOR kinase inhibitors Torin-2-on EBD after stenting. At 60 days after stent placement, everolimus-eluting stents demonstrated large areas of Evans blue dye staining and evidence of p120 VE-CAD dissociation consistent with EBD. As proof of concept of the role of EBD in neoatherosclerosis, 100 days after stenting, animals were fed an enriched cholesterol diet for an addnl. 30 days. Everolimus-eluting stents demonstrated significantly more macrophage infiltration (consistent with neoatherosclerosis) compared with both bare metal stents and Torin-2-eluting stent. Our results pinpoint interactions between FKBP12.6 and canonical mTOR inhibitors as a major cause of vascular permeability and neoatherosclerosis, which can be overcome by using mTOR kinase inhibitors.

Arteriosclerosis, Thrombosis, and Vascular Biology published new progress about Atherosclerosis. 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

Mosharaf, Parvez Md.; Reza, Selim Md.; Kibria, Kaderi Md.; Ahmed, Fee Faysal; Kabir, Hadiul Md.; Hasan, Sohel; Mollah, Nurul Haque Md. published the artcile< Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is drug repurposing SARSCoV2 infection computational gene protein miRNA.

Abstract: The pandemic threat of COVID-19 has severely destroyed human life as well as the economy around the world. Although, the vaccination has reduced the outspread, but people are still suffering due to the unstable RNA sequence patterns of SARS-CoV-2 which demands supplementary drugs. To explore novel drug target proteins, in this study, a transcriptomics RNA-Seq data generated from SARS-CoV-2 infection and control samples were analyzed. We identified 109 differentially expressed genes (DEGs) that were utilized to identify 10 hub-genes/proteins (TLR2, USP53, GUCY1A2, SNRPD2, NEDD9, IGF2, CXCL2, KLF6, PAG1 and ZFP36) by the protein-protein interaction (PPI) network anal. The GO functional and KEGG pathway enrichment analyses of hub-DEGs revealed some important functions and signaling pathways that are significantly associated with SARS-CoV-2 infections. The interaction network anal. identified 5 TFs proteins and 6 miRNAs as the key regulators of hub-DEGs. Considering 10 hub-proteins and 5 key TFs-proteins as drug target receptors, we performed their docking anal. with the SARS-CoV-2 3CL protease-guided top listed 90 FDA approved drugs. We found Torin-2, Rapamycin, Radotinib, Ivermectin, Thiostrepton, Tacrolimus and Daclatasvir as the top ranked seven candidate drugs. We investigated their resistance performance against the already published COVID-19 causing top-ranked 11 independent and 8 protonated receptor proteins by mol. docking anal. and found their strong binding affinities, which indicates that the proposed drugs are effective against the state-of-the-arts alternatives independent receptor proteins also. Finally, we investigated the stability of top three drugs (Torin-2, Rapamycin and Radotinib) by using 100 ns MD-based MM-PBSA simulations with the two top-ranked proposed receptors (TLR2, USP53) and independent receptors (IRF7, STAT1), and observed their stable performance. Therefore, the proposed drugs might play a vital role for the treatment against different variants of SARS-CoV-2 infections.

Scientific Reports published new progress about Animal gene Role: ANT (Analyte), BSU (Biological Study, Unclassified), ANST (Analytical Study), BIOL (Biological Study) (CXCL2). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Recommanded Product: 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

Hamed, Mohamed; Gladbach, Yvonne; Moeller, Steffen; Fischer, Sarah; Ernst, Mathias; Struckmann, Stephan; Storch, Alexander; Fuellen, Georg published the artcile< A workflow for the integrative transcriptomic description of molecular pathology and the suggestion of normalizing compounds, exemplified by Parkinson's disease>, Reference of 1223001-51-1, the main research area is miRNA mRNA Parkinson disease mol pathol.

The volume of mol. observations on human diseases in public databases is continuously increasing at accelerating rates. A bottleneck is their computational integration into a coherent description, from which researchers may derive new well-founded hypotheses. Also, the need to integrate data from different technologies (genetics, coding and regulatory RNA, proteomics) emerged in order to identify biomarkers for early diagnosis and prognosis of complex diseases and therefore facilitating the development of novel treatment approaches. We propose here a workflow for the integrative transcriptomic description of the mol. pathol. in Parkinsons’s Disease (PD), including suggestions of compounds normalizing disease-induced transcriptional changes as a paradigmatic example. We integrated gene expression profiles, miRNA signatures, and publicly available regulatory databases to specify a partial model of the mol. pathophysiol. of PD. Six genetic driver elements (2 genes and 4 miRNAs) and several functional network modules that are associated with PD were identified. Functional modules were assessed for their statistical significance, cellular functional homogeneity, literature evidence, and normalizing small mols. In summary, our workflow for the joint regulatory anal. of coding and non-coding RNA, has the potential to yield clin. as well as biol. relevant information, as demonstrated here on PD data.

Scientific Reports published new progress about Auxilin 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Sun, Wei; Tanaka, Takeshi Q.; Magle, Crystal T.; Huang, Wenwei; Southall, Noel; Huang, Ruili; Dehdashti, Seameen J.; McKew, John C.; Williamson, Kim C.; Zheng, Wei published the artcile< Chemical signatures and new drug targets for gametocytocidal drug development>, Electric Literature of 1223001-51-1, the main research area is antimalarial agent therapeutic target gametocyte Plasmodium malaria.

Control of parasite transmission is critical for the eradication of malaria. However, most antimalarial drugs are not active against P. falciparum gametocytes, responsible for the spread of malaria. Consequently, patients can remain infectious for weeks after the clearance of asexual parasites and clin. symptoms. Here we report the identification of 27 potent gametocytocidal compounds (IC50 < 1 μM) from screening 5,215 known drugs and compounds All these compounds were active against three strains of gametocytes with different drug sensitivities and geog. origins, 3D7, HB3 and Dd2. Cheminformatic anal. revealed chem. signatures for P. falciparum sexual and asexual stages indicative of druggability and suggesting potential targets. Torin 2, a top lead compound (IC50 = 8 nM against gametocytes in vitro), completely blocked oocyst formation in a mouse model of transmission. These results provide critical new leads and potential targets to expand the repertoire of malaria transmission-blocking reagents. Scientific Reports published new progress about 5-HT2A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

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