Heterocyclic Building Blocks-Naphthyridine

Zhao, Zhongwei; Zhang, Dengke; Wu, Fazong; Tu, Jianfei; Song, Jingjing; Xu, Min; Ji, Jiansong published the artcile< Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression>, Related Products of 6882-68-4, the main research area is hepatocellular carcinoma growth sophoridine lenvatinib RAS MEK ERK VEGFR2; VEGFR2; hepatocellular carcinoma; lenvatinib resistance; sophoridine.

This study aims to investigate the underlying mechanism of lenvatinib resistance and explore the potential drug to improve the treatment for lenvatinib-resistant (LR) HCC. Here, we developed two human LR HCC cell lines by culturing with long-term exposure to lenvatinib. Results showed that the vascular endothelial growth factor receptors (VEGFR)2 expression and its downstream RAS/MEK/ERK signalling were obviously up-regulated in LR HCC cells, whereas the expression of VEGFR1, VEGFR3, FGFR1-4 and PDGFRα/β showed no difference. Furthermore, ETS-1 was identified to be responsible for VEGFR2 mediated lenvatinib resistance. The cell models were further used to explore the potential strategies for restoration of sensitivity of lenvatinib. Sophoridine, an alkaloid extraction, inhibited the proliferation, colony formation, cell migration and increased apoptosis of LR HCC cells. In vivo and in vitro results showed Sophoridine could further sensitize the therapeutic of lenvatinib against LR HCC. Mechanism studies revealed that Sophoridine decreased ETS-1 expression to down-regulate VEGFR2 expression along with downstream RAS/MEK/ERK axis in LR HCC cells. Hence, our study revealed that up-regulated VEGFR2 expression could be a predicator of the resistance of lenvatinib treatment against HCC and provided a potential candidate to restore the sensitivity of lenvatinib for HCC treatment.

Journal of Cellular and Molecular Medicine published new progress about Angiogenesis. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Related Products of 6882-68-4.

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

Wang, Congren; Wang, Xuejin; Su, Zijian; Fei, Hongjiang; Liu, Xiaoyu; Pan, Qunxiong published the artcile< The novel mTOR inhibitor Torin-2 induces autophagy and downregulates the expression of UHRF1 to suppress hepatocarcinoma cell growth>, Computed Properties of 1223001-51-1, the main research area is mTOR Torin2 autophagy UHRF1 DNMT1 hepatocarcinoma anticancer.

Mammalian target of rapamycin (mTOR) is frequently upregulated in hepatocellular carcinoma (HCC). Blockage of mTOR was found to induce marked reduction in HCC growth in preclin. models. In the present study, we tested a novel mTOR inhibitor, Torin-2, for its antitumor efficacy in HCC cell lines Hep G2, SNU-182 and Hep 3B2.1-7. The HCC cell lines were cultured in vitro. These cells were treated with Torin-2. Cell apoptosis was evaluated by Annexin V staining. Cell proliferation and cell cycle progression were determined by Ki67 staining and propidium iodide staining, resp. mTOR signaling, autophagy induction and expression of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) were assessed by western blot anal. The UHRF1 mRNA level was determined by real-time PCR. We found that Torin-2 effectively suppressed the growth and survival of HCC cell lines, demonstrated by reduced proliferation and a high rate of apoptosis. Further study elucidated that in addition to blocking mTOR complex 1 (mTORC1)-associated cell cycle progression and induction of autophagy, Torin-2 downregulated transcription of UHRF1, an essential regulator of DNA methylation that is highly expressed in HCC cell lines. Consistently, the level of DNA (cytosine-5)-methyltransferase 1 (DNMT1) was higher after treatment of the HCC cell lines with Torin-2. The downregulation of UHRF1 by Torin-1 was partially due to a decrease in the UHRF1 mRNA level. Torin-2 effectively inhibited HCC cell proliferation through induction of autophagy. Torin-2-induced downregulation of UHRF1 expression may also contribute to its antitumor effect. Our research provides new clues regarding the antitumor effects of Torin-2 and sheds light on a novel therapeutic approach for HCC.

Oncology Reports published new progress about Antitumor agents. 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

Tang, Sheng; Wang, Can; Li, Ying-Hong; Niu, Tian-Yu; Zhang, Yuan-Hui; Pang, Yu-Dong; Wang, Yan-Xiang; Kong, Wei-Jia; Song, Dan-Qing published the artcile< Structure-activity relationship and hypoglycemic activity of tricyclic matrines with advantage of treating diabetic nephropathy>, Electric Literature of 6882-68-4, the main research area is diabetic nephropathy tricyclic matrinic hypoglycemic SAR pharmacodynamics glycolysis; Diabetic nephropathy; Hypoglycemic; Pharmacodynamics; Tricyclic matrinic; structure−activity relationship.

Forty-three tricyclic matrinic derivatives with a unique scaffold were prepared and evaluated for their stimulation effects on glucose consumption in HepG2 cells. The structure-activity relationship was systematically elucidated for the first time. Among them, compound 17a(I) exhibited the most promising potency, and dose-dependently increased glucose consumption in L6 myotubes. It significantly lowered blood glucose, glucosylated Hb and AGE level, and improved glucose tolerance and insulin resistance in KK-Ay mice as well. More importantly, 17a effectively ameliorated diabetic nephropathy (DN), as indicated by the improvement of renal function and pathol. changes, and decrease of urinary protein. Furthermore, 17a could induce glycolysis but suppressed aerobic oxidation of glucose, in a similar mechanism to Metform. Our results indicated that in addition to hyperglycemia, 17a may be developed to treat diabetic complication such as DN.

European Journal of Medicinal Chemistry published new progress about Advanced glycosylation end products Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Electric Literature of 6882-68-4.

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

Weydert, Zoe; Lal-Nag, Madhu; Mathews-Greiner, Lesley; Thiel, Christoph; Cordes, Henrik; Kupfer, Lars; Guye, Patrick; Kelm, Jens M.; Ferrer, Marc published the artcile< A 3D Heterotypic Multicellular Tumor Spheroid Assay Platform to Discriminate Drug Effects on Stroma versus Cancer Cells>, Synthetic Route of 1223001-51-1, the main research area is cancer cell fibroblast 3D heterotypic tumor spheroid assay; 3D heterotypic spheroids; population-bound bioluminescence reporter; screening; stroma; therapeutic index.

Three-dimensional (3D) cell culture models are thought to mimic the physiol. and pharmacol. properties of tissues in vivo more accurately than two-dimensional cultures on plastic dishes. For the development of cancer therapies, 3D spheroid models are being created to reflect the complex histol. and physiol. of primary tumors with the hopes that drug responses will be more similar to and as predictive as those obtained in vivo. The effect of addnl. cell types in tumors, such as stromal cells, and the resulting heterotypic cell-cell crosstalk can be investigated in these heterotypic 3D cell cultures. Here, a high-throughput screening-compatible drug testing platform based on 3D multicellular spheroid models is described that enables the parallel assessment of toxicity on stromal cells and efficacy on cancer cells by drug candidates. These heterotypic microtissue tumor models incorporate NIH3T3 fibroblasts as stromal cells that are engineered with a reporter gene encoding secreted NanoLUC luciferase. By tracking the NanoLUC signal in the media over time, a time-related measurement of the cytotoxic effects of drugs on stromal cells over the cancer cells was possible, thus enabling the identification of a therapeutic window. An in vitro therapeutic index parameter is proposed to help distinguish and classify those compounds with broad cytotoxic effects vs. those that are more selective at targeting cancer cells.

SLAS Discovery published new progress about Bioassay. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Synthetic Route of 1223001-51-1.

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

Kosowicz, John G.; Lee, Jaeyeun; Peiffer, Brandon; Guo, Zufeng; Chen, Jianmeng; Liao, Gangling; Hayward, S. Diane; Liu, Jun O.; Ambinder, Richard F. published the artcile< Drug modulators of b cell signaling pathways and epstein-barr virus lytic activation>, Electric Literature of 1223001-51-1, the main research area is herpesvirus 4 activation b cell signaling pathway drug modulator; B cell receptor pathway; Epstein-Barr virus; cyclosporine; dasatinib; ibrutinib; idelalisib; lytic infection; mTOR; rapamycin; tacrolimus.

Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematol. malignancies, block BCR-mediated lytic induction at clin. relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib.

Journal of Virology published new progress about Antiviral agents. 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

Zhang, Shilong; Liu, Yungen; Xing, Fangrong; Che, Chi-Ming published the artcile< Direct preparation of unprotected aminimides (R3N+-NH-) from natural aliphatic tertiary alkaloids (R3N) by [Mn(TDCPP)Cl]-catalysed N-amination reaction>, Synthetic Route of 6882-68-4, the main research area is unprotected aminimide preparation antitumor human; natural aliphatic tertiary alkaloid amination manganese complex catalyst; manganese complex preparation.

A panel of natural aliphatic tertiary alkaloids were directly converted to unprotected aminimides via [Mn(TDCPP)Cl]-catalyzed N-amination reaction using O-(2,4-dinitrophenyl)hydroxylamine as the nitrogen source in up to 98% yields under mild reaction conditions.

Chemical Communications (Cambridge, United Kingdom) published new progress about Alkaloids Role: PAC (Pharmacological Activity), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 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

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