Tag: M.W=400-600

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

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

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

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

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

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

Yin, Liqing; Zhang, Yongzhu; Azi, Fidelis; Tekliye, Mekonen; Zhou, Jianzhong; Liu, Xiaoli; Dong, Mingsheng; Xia, Xiudong published the artcile< Neuroprotective Potency of Tofu Bio-Processed Using Actinomucorelegans against Hypoxic Injury Induced by Cobalt Chloride in PC12 Cells>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is cobalt chloride actinomucorelegan hypoxic injury Tofu bioprocessed neuroprotective potency; autophagy; cell apoptosis; cell arrest; oxidative stress; soybean products.

Fermented soybean products have attracted great attention due to their health benefits. In the present study, the hypoxia-injured PC12 cells induced by cobalt chloride (CoCl2) were used to evaluate the neuroprotective potency of tofu fermented by Actinomucor elegans (FT). Results indicated that FT exhibited higher phenolic content and antioxidant activity than tofu. Moreover, most soybean isoflavone glycosides were hydrolyzed into their corresponding aglycons during fermentation FT demonstrated a significant protective effect on PC12 cells against hypoxic injury by maintaining cell viability, reducing lactic dehydrogenase leakage, and inhibiting oxidative stress. The cell apoptosis was significantly attenuated by the FT through down-regulation of caspase-3, caspases-8, caspase-9, and Bax, and up-regulation of Bcl-2 and Bcl-xL. S-phase cell arrest was significantly inhibited by the FT through increasing cyclin A and decreasing the p21 protein level. Furthermore, treatment with the FT activated autophagy, indicating that autophagy possibly acted as a survival mechanism against CoCl2-induced injury. Overall, FT offered a potential protective effect on nerve cells in vitro against hypoxic damage.

Molecules published new progress about Actinomucor elegans. 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

Mosaddeghi, Pouria; Eslami, Mahboobeh; Farahmandnejad, Mitra; Akhavein, Mahshad; Ranjbarfarrokhi, Ratin; Khorraminejad-Shirazi, Mohammadhossein; Shahabinezhad, Farbod; Taghipour, Mohammadjavad; Dorvash, Mohammadreza; Sakhteman, Amirhossein; Zarshenas, Mohammad M.; Nezafat, Navid; Mobasheri, Meysam; Ghasemi, Younes published the artcile< A systems pharmacology approach to identify the autophagy-inducing effects of Traditional Persian medicinal plants>, HPLC of Formula: 1223001-51-1, the main research area is autophagy systems pharmacol medicinal plant Persia.

Abstract: Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy. To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references The known phytochems. of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment anal. of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein-protein interaction (PPI) network of the targets was reconstructed. Network centrality anal. of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction.

Scientific Reports published new progress about Acute respiratory distress syndrome. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, HPLC of Formula: 1223001-51-1.

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

Amin, Anubhav G.; Jeong, Seung Won; Gillick, John L.; Sursal, Tolga; Murali, Raj; Gandhi, Chirag D.; Jhanwar-Uniyal, Meena published the artcile< Targeting the mTOR pathway using novel ATP-competitive inhibitors, Torin1, Torin2 and XL388, in the treatment of glioblastoma>, Electric Literature of 1223001-51-1, the main research area is mTOR Torin1 Torin2 XL388 glioblastoma; PRAS40; Torin1; Torin2; glioblastoma; mTOR; mTOR inhibitors.

Mechanistic target of rapamycin (mTOR), which functions via two multiprotein complexes termed mTORC1 and mTORC2, is positioned in the canonical phosphoinositide 3-kinase-related kinase (PI3K)/AKT (PI3K/AKT) pathways. These complexes exert their actions by regulating other important kinases, such as 40S ribosomal S6 kinases (S6K), eukaryotic translation initiation factor 4E (elF4E)-binding protein 1 (4E-BP1) and AKT, to control cell growth, proliferation, migration and survival in response to nutrients and growth factors. Glioblastoma (GB) is a devastating form of brain cancer, where the mTOR pathway is deregulated due to frequent upregulation of the Receptor Tyrosine Kinase/PI3K pathways and loss of the tumor suppressor phosphatase and tensin homolog (PTEN). Rapamycin and its analogs were less successful in clin. trials for patients with GB due to their incomplete inhibition of mTORC1 and the activation of mitogenic pathways via neg. feedback loops. Here, the effects of selective ATP-competitive dual inhibitors of mTORC1 and mTORC2, Torin1, Torin2 and XL388, are reported. Torin2 exhibited concentration-dependent pharmacodynamic effects on inhibition of phosphorylation of the mTORC1 substrates S6KSer235/236 and 4E-BP1Thr37/46 as well as the mTORC2 substrate AKTSer473 resulting in suppression of tumor cell migration, proliferation and S-phase entry. Torin1 demonstrated similar effects, but only at higher doses. XL388 suppressed cell proliferation at a higher dose, but failed to inhibit cell migration. Treatment with Torin1 suppressed phosphorylation of proline rich AKT substrate of 40 kDa (PRAS40) at Threonine 246 (PRAS40Thr246) whereas Torin2 completely abolished it. XL388 treatment suppressed the phosphorylation of PRAS40Thr246 only at higher doses. Drug resistance anal. revealed that treatment of GB cells with XL388 rendered partial drug resistance, which was also seen to a lesser extent with rapamycin and Torin1 treatments. However, treatment with Torin2 completely eradicated the tumor cell population. These results strongly suggest that Torin2, compared to Torin1 or XL388, is more effective in suppressing mTORC1 and mTORC2, and therefore in the inhibition of the GB cell proliferation, dissemination and in overcoming resistance to therapy. These findings underscore the significance of Torin2 in the treatment of GB.

International Journal of Oncology published new progress about Antitumor 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

Vogel, Kara R.; Ainslie, Garrett R.; Gibson, K. Michael published the artcile< mTOR inhibitors rescue premature lethality and attenuate dysregulation of GABAergic/glutamatergic transcription in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is rapamycin mTOR inhibitor GABA glutamate succinate semialdehyde dehydrogenase deficiency.

Recent studies have identified a role for supraphysiol. gamma-aminobutyric acid (GABA) in the regulation of mechanistic target of rapamycin (mTOR), a protein kinase with pleiotropic roles in cellular development and homeostasis, including integration of growth factors and nutrient sensing and synaptic input in neurons (Lakhani et al. 2014; Vogel et al. 2015). Aldehyde dehydrogenase 5a1-deficient (aldh5a1-/-) mice, the murine orthologue of human succinic semialdehyde dehydrogenase deficiency (SSADHD), manifest increased GABA that disrupts mitophagy and increases mitochondria number with enhanced oxidant stress. Treatment with the mTOR inhibitor, rapamycin, significantly attenuates these GABA-related anomalies. We extend those studies through characterization of addnl. rapamycin analog (rapalog) agents including temsirolimus, dual mTOR inhibitors [Torin 1 and 2 (Tor 1/ Tor 2), Ku-0063794, and XL-765], as well as mTOR-independent autophagy inducers [trehalose, tat-Beclin 1, tacrolimus (FK-506), and NF-449) in aldh5a1-/- mice. Rapamycin, Tor 1, and Tor 2 rescued these mice from premature lethality associated with status epilepticus. XL-765 extended lifespan significantly and induced weight gain in aldh5a1-/- mice; untreated aldh5a1-/- mice failed to increase body mass. Expression profiling of animals rescued with Tor 1/Tor 2 and XL-765 revealed multiple instances of pharmacol. compensation and/or correction of GABAergic and glutamatergic receptors, GABA/glutamate transporters, and GABA/glutamate-associated proteins, with Tor 2 and XL-765 showing optimal outcomes. Our studies lay the groundwork for further evaluation of mTOR inhibitors in aldh5a1-/- mice, with therapeutic ramifications for heritable disorders of GABA and glutamate neurotransmission.

Journal of Inherited Metabolic Disease published new progress about Adenosine A2A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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