Month: October 2022

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>, SDS of cas: 1223001-51-1, 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 Reports published new progress about Aurora kinase inhibitors. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, SDS of cas: 1223001-51-1.

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

Zhang, Wan-Ying; Chen, Ying; Zhang, Miao-Miao; Zhang, Guo-Wei published the artcile< Molecular mechanism prediction analysis of compound Kushen injection in the treatment of COVID-19 based on network pharmacology and molecular docking>, Application In Synthesis of 6882-68-4, the main research area is COVID 19 compound Kushen injection.

As 1 of the 8 effective traditional Chinese medicines for the treatment of atypical pneumonia, compound Kushen injection (CKI) played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003. CKI is known to inhibit inflammation, and its main chem. components, namely matrine and oxymatrine, can promote Th cells to recognize and eliminate viruses. In this study, network pharmacol. and mol. docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019. The Traditional Chinese Medicine Systems Pharmacol. Database and Anal. Platform and other related literature were used to screen CKI’s active ingredients in the blood. Traditional Chinese Medicine Systems Pharmacol. Database and Anal. Platform, Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients. The ingredient-target network was constructed using the Cytoscape software. The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets. Sophocarpine, sophoridine, matrine, (+)-allomatrine, AIDS211310, and sophranol were the 6 active ingredients. After docking the active ingredients with severe acute respiratory syndrome coronavirus 2 3CL hydrolase and angiotensin-converting enzyme 2 (ACE2), they displayed suitable affinity, which could block viral replication and its binding to ACE2. The key targets mainly involved inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Gene Ontol. enrichment anal. mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway. The Kyoto Encyclopedia of Genes and Genome pathway enrichment anal. mainly indicated steroid hormone biosynthesis and the TNF signaling pathway. The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors. They regulate the IL-6-mediated signaling pathway, TNF signaling pathway, and steroid hormone biosynthesis, thereby initiating therapeutic responses against COVID-19.

Traditional Medicine Research published new progress about COVID-19. 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

Zamfirescu, Radu C.; Day, Margot L.; Morris, Michael B. published the artcile< mTORC1/2 signaling is downregulated by amino acid-free culture of mouse preimplantation embryos and is only partially restored by amino acid readdition>, Formula: C24H15F3N4O, the main research area is mTORC1 mTORC2 signaling amino acid mouse preimplantation embryo; Akt; amino acids; mTORC1; mouse preimplantation embryo; proline.

Development of the mammalian preimplantation embryo is influenced by autocrine/paracrine factors and the availability of nutrients. Deficiencies of these during in vitro culture reduce the success of assisted reproductive technologies. The mechanistic target of rapamycin complex 1 (mTORC1) pathway integrates external and internal signals, including those by amino acids (AAs), to promote normal preimplantation development. For this reason, AAs are often included in embryo culture media. In this study, we examined how withdrawal and addition of AAs to culture media modulate mTORC1 pathway activity compared with its activity in mouse embryos developed in vivo. Phosphorylation of signaling components downstream of mTORC1, namely, p70 ribosomal protein S6 kinase (p70S6K), ribosomal protein S6, and 4E binding protein 1 (4E-BP1), and that of protein kinase B (Akt), which lies upstream of mTORC1, changed significantly across stages of embryos developed in vivo. For freshly isolated blastocysts placed in vitro, the absence of AAs in the culture medium, even for a few hours, decreased mTORC1 signaling, which could only be partially restored by their addition Long-term culture of early embryos to blastocysts in the absence of AAs decreased mTORC1 signaling to a greater extent and again this could only be partially restored by their inclusion. This failure to fully restore is probably due to decreased phosphatidylinositol 3-kinase (PI3K)/Akt/mTORC2 signaling in culture, as indicated by decreased P-AktS473. MTORC2 lies upstream of mTORC1 and is insensitive to AAs, and its reduced activity probably results from loss of maternal/autocrine factors. These data highlight reduced mTORC1/2 signaling activity correlating with compromised development in vitro and show that the addition of AAs can only partially offset these effects.

American Journal of Physiology published new progress about Actins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Jhanwar-Uniyal, Meena; Dominguez, Jose F.; Mohan, Avinash L.; Tobias, Michael E.; Gandhi, Chirag D. published the artcile< Disentangling the signaling pathways of mTOR complexes, mTORC1 and mTORC2, as a therapeutic target in glioblastoma>, SDS of cas: 1223001-51-1, the main research area is glioblastoma therapeutic target disentangling signaling mTORC1 mTORC2; Glioblastoma; mTOR; mTORC1 mTORC2.

Aberrant signaling of mechanistic target of rapamycin (mTOR′ aka mammalian target of rapamycin) is shown to be linked to tumorigenesis of numerous malignancies including glioblastoma (GB). Glioblastoma mTOR is a serine threonine kinase that functions by forming two multiprotein complexes. There complexes are named mTORC1 and mTORC2 and downstream activated substrate execute cellular and metabolic functions. This signaling cascade of PI3K/AKT/mTOR is often upregulated due to frequent loss of the tumor suppressor PTEN, a phosphatase that functions antagonistically to PI3K. mTOR regulates cell growth, motility, and metabolism by forming two multiprotein complexes, mTORC1 and mTORC2, which are composed of special binding partners. These complexes are sensitive to distinct stimuli. mTORC1 is sensitive to nutrients and mTORC2 is regulated via PI3K and growth factor signaling. Since rapamycin and its analog are less effective in treatment of GB, we used novel ATP-competitive dual inhibitors of mTORC1 and mTORC2, namely, Torin1, Torin2, and XL388. Torin1 showed similar effects only at higher doses. Another small mol. compound, XL388 suppressed cell proliferation at a higher dose but failed to inhibit cell migration. In addition, formulation of third generation mTOR inhibitor “”Rapalink-1″” may provide new aspects to target mTOR pathways. Numerous inhibitors are currently being used in clin. trials that are aimed to target activated mTOR pathways.

Advances in Biological Regulation published new progress about AKT-interacting protein AKTIP Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, SDS of cas: 1223001-51-1.

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

Jia, Xu; Zhang, Hanghang; Jiang, Xiangfu; Lu, Yaling; Liu, Wenjie; Yu, Jianna published the artcile< Profiling and quantitation of alkaloids in different parts of Sophora alopecuroides L. extracts by high-performance liquid chromatography with electrospray ionisation ion mobility spectrometry detection>, Application of C15H24N2O, the main research area is Sophora alopecuroides extract alkaloid HPLC electrospray ionization MS; HPLC-IMS; alkaloids; ion mobility spectrometry.

Ambient pressure electrospray ionisation ion mobility spectrometry coupled to high-performance liquid chromatog. (HPLC) was used to detect alkaloids from different parts of Sophora alopecuroides L. extracts Multiplexing ion mobility spectrometry (IMS) was used to improve the signal-to-noise ratio while maintaining high resolving power for the detecting of eluents from HPLC separation The alkaloids profile and distribution are demonstrated by retention time-drift time two-dimensional spaces, and the contents of five major alkaloids including sophoridine, sophocarpine, cytisine, aloperine, and matrine were determined in the leaf, skin, stem, seed kernel, and seed husk using the HPLC-IMS method. This method offers extra separation ability to isomers such as matrine and sophocarpine, which can be difficult to distinguish by mass spectrometry. The reduced mobilities for cytisine, sophoridine, sophocarpine, matrine, and aloperine are 0.828, 0.718, 0.731, 0.725, and 0.769 cm2/V/s, resp. The limits of detection are 0.553, 0.488, 0.479, 0.484, and 0.513 ug/mL. This method adds extra separation ability to HPLC to resolve co-eluted peaks and provides another qual. parameter besides HPLC retention time.

Phytochemical Analysis published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Application of C15H24N2O.

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

Udayakumar, Durga; Pandita, Raj K.; Horikoshi, Nobuo; Liu, Yan; Liu, Qingsong; Wong, Kwok-Kin; Hunt, Clayton R.; Gray, Nathanael S.; Minna, John D.; Pandita, Tej K.; Westover, Kenneth D. published the artcile< Torin2 suppresses ionizing radiation-induced DNA damage repair>, Electric Literature of 1223001-51-1, the main research area is ionizing radiation Torin2 mTOR inhibitor DNA damage repair cancer.

Several classes of inhibitors of the mammalian target of rapamycin (mTOR) have been developed based on its central role in sensing growth factor and nutrient levels to regulate cellular metabolism However, its ATP-binding site closely resembles other phosphatidylinositol 3-kinase-related kinase (PEKK) family members, resulting in reactivity with these targets that may also be therapeutically useful. The ATP- competitive mTOR inhibitor, Torin2, shows biochem. activity against the DNA repair-associated proteins ATM, ATR and DNA-PK, which raises the possibility that Torin2 and related compounds might radiosensitize cancerous tumors. In this study Torin2 was also found to enhance ionizing radiation-induced cell killing in conditions where ATM was dispensable, confirming the requirement for multiple PIKK targets. Moreover, Torin2 did not influence the initial appearance of γ-H2AX foci after irradiation but significantly delayed the disappearance of radiation-induced γ-H2AX foci, indicating a DNA repair defect. Torin2 increased the number of radiation-induced S-phase specific chromosome aberrations and reduced the frequency of radiation-induced CLIP and Rad51 foci formation, suggesting that Torin2 works by blocking homologous recombination (HR)-mediated DNA repair resulting in an S-phase specific DNA repair defect. We conclude that radiosensitization of tumor cells by Torin2 is associated with disrupting ATR- and ATM-dependent DNA damage responses.

Radiation Research published new progress about Attenuated total reflection. 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

Kim, Sun Woong; Kim, Hye-In; Thapa, Bikash; Nuwromegbe, Selikem; Lee, Keunwook published the artcile< Critical role of mTORC2-Akt signaling in TGF-β1-induced myofibroblast differentiation of human pterygium fibroblasts>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is pterygium fibroblast differentiation mTORC2 Akt TGF beta 1.

In this study, we investigated the role of the mechanistic target of rapamycin (mTOR) in regulating TGF-β1-induced myofibroblastic responses in human pterygium fibroblasts (HPFs) and elucidated the relative contributions of mTOR signaling components. HPFs were pretreated with the mTOR inhibitors rapamycin and Torin2, and TGF-β1-induced expression of profibrotic markers, including α-smooth muscle actin (α-SMA) and fibronectin, was evaluated. The mTOR active-site inhibitor Torin2, which suppresses both mTORC1 and mTORC2 activity in HPFs, inhibited TGF-β1-induced expression of α-SMA and fibronectin. The induction of α-SMA and fibronectin in HPFs was abrogated by RNA interference-mediated knockdown of rictor but was only moderately affected by raptor knockdown. Akt inhibition mimicked the effect of Torin2 and rictor knockdown on myofibroblast differentiation of HPFs. mTOR inhibition potently reduced the contractile ability of HPFs in collagen gel contraction assays. This study found that mTOR signaling promoted profibrotic activation of HPFs and confirmed the importance of the mTORC2-Akt axis in TGF-β1-induced myofibroblast differentiation. Therefore, our study may open up new avenues for the development of novel therapeutic strategies involving targeting of mTOR signaling to treat pterygium.

Investigative Ophthalmology & Visual Science published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (EDA-FN). 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

Awasthi, Ankita; Kumar, Pharvendra; Srikanth, Chittur V.; Sahi, Shakti; Puria, Rekha published the artcile< Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is colorectal cancer Torin2 2 6 dihydroxyacetophenone antitumor; Docking; Drug development; Kinase inhibitor; Natural Compound; mTOR.

Colorectal cancer (CRC) is one of the most prevalent cancers diagnosed worldwide. Despite recent advances, resistance to cytotoxic and targeted therapy remains one of the greatest challenges in long-term management of colorectal cancer therapy. Recently established role of mTOR signaling in proliferation of CRC has incited for evaluation of mTOR kinase specific inhibitors in CRC therapy. Second generation mTOR kinase inhibitors including Torin2 has demonstrated efficient anticancer properties against variety of cancers and are in various stages of drug development. The time and financial constraints concomitant from discovery to development of efficient chem. inhibitors has redirected attention towards investigation of wide spread naturally occurring largely inexpensive compounds for their therapeutic potential. One such naturally occurring compound acetophenone derivative polyphenolic compound 2, 6-Dihydroxyacetophenone (DHAP) inhibits cell growth in different conditions. We investigated anticancer properties of both Torin2 and DHAP against colorectal cancer in HCT8 cell lines. Both Torin2 and DHAP inhibited growth of CRC cells at different concentrations by restricting multiple cellular functions e.g., cell cycle progression, cell migration and induced apoptosis. Treatment of HCT8 cells with natural compound DHAP resulted in reduced expression of mTOR pathway specific genes p70S6K1 and AKT1. In silico docking studies showed affinity of DHAP to mTOR kinase like Torin2. Taken together, our result vouches for role of Torin2 in CRC therapy and recommends DHAP an mTOR inhibitor, as a potential lead in the development of new therapeutic regimes against colorectal cancer.

Pathology & Oncology Research published new progress about Acetophenones Role: PAC (Pharmacological Activity), THU (Therapeutic Use), BIOL (Biological Study), USES (Uses). 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

Dillenburg-Pilla, Patricia; Patel, Vyomesh; Mikelis, Constantinos M.; Zarate-Blades, Carlos Rodrigo; Doci, Colleen L.; Amornphimoltham, Panomwat; Wang, Zhiyong; Martin, Daniel; Leelahavanichkul, Kantima; Dorsam, Robert T.; Masedunskas, Andrius; Weigert, Roberto; Molinolo, Alfredo A.; Gutkind, J. Silvio published the artcile< SDF-1/CXCL12 induces directional cell migration and spontaneous metastasis via a CXCR4/Gαi/mTORC1 axis>, Formula: C24H15F3N4O, the main research area is CXCR4 Galphai mTORC1 axis SDF1 CXCL12 cell migration metastasis; cancer; chemotaxis; lymphangiogenesis; mTOR; rapamycin.

Multiple human malignancies rely on C-X-C motif chemokine receptor type 4 (CXCR4) and its ligand, SDF-1/CXCL12 (stroma cell-derived factor 1/C-X-C motif chemokine 12), to metastasize. CXCR4 inhibitors promote the mobilization of bone marrow stem cells, limiting their clin. application for metastasis prevention. We investigated the CXCR4-initiated signaling circuitry to identify new potential therapeutic targets. We used HeLa human cancer cells expressing high levels of CXCR4 endogenously. We found that CXCL12 promotes their migration in Boyden chamber assays and single cell tracking. CXCL12 activated mTOR (mechanistic target of rapamycin) potently in a pertussis-sensitive fashion. Inhibition of mTOR complex 1 (mTORC1) by rapamycin [drug concentration causing 50% inhibition (IC50) = 5 nM] and mTORC1/mTORC2 by Torin2 (IC50 = 6 nM), or by knocking down key mTORC1/2 components, Raptor and Rictor, resp., decreased directional cell migration toward CXCL12. We developed a CXCR4-mediated spontaneous metastasis model by implanting HeLa cells in the tongue of SCID-NOD mice, in which 80% of the animals develop lymph node metastasis. It is surprising that mTORC1 disruption by Raptor knockdown was sufficient to reduce tumor growth by 60% and spontaneous metastasis by 72%, which were nearly abolished by rapamycin. In contrast, disrupting mTORC2 had no effect in tumor growth or metastasis compared with control short hairpin RNAs. These data suggest that mTORC1 may represent a suitable therapeutic target in human malignancies using CXCR4 for their metastatic spread.

FASEB Journal published new progress about Angiogenesis. 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

Quiros-Fernandez, Isaac; Figueroa-Protti, Lucia; Arias-Arias, Jorge L.; Brenes-Cordero, Norman; Siles, Francisco; Mora, Javier; Mora-Rodriguez, Rodrigo Antonio published the artcile< Perturbation-Based Modeling Unveils the Autophagic Modulation of Chemosensitivity and Immunogenicity in Breast Cancer Cells>, Application In Synthesis of 1223001-51-1, the main research area is perturbation modeling unveil autophagic modulation chemosensitivity immunogenicity breast cancer; autophagy; chemotherapy; immunogenic cell death; perturbation-based modeling.

In the absence of new therapeutic strategies, chemotherapeutic drugs are the most widely used strategy against metastatic breast cancer, in spite of eliciting multiple adverse effects and having low responses with an average 5-yr patient survival rate. Among the new therapeutic targets that are currently in clin. trials, here, we addressed the association between the regulation of the metabolic process of autophagy and the exposure of damage-associated mol. patterns associated (DAMPs) to immunogenic cell death (ICD), which has not been previously studied. After validating an mCHR-GFP tandem LC3 sensor capacity to report dynamic changes of the autophagic metabolic flux in response to external stimuli and demonstrating that both basal autophagy levels and response to diverse autophagy regulators fluctuate among different cell lines, we explored the interaction between autophagy modulators and chemotherapeutic agents in regards of cytotoxicity and ICD using three different breast cancer cell lines. Since these interactions are very complex and variable throughout different cell lines, we designed a perturbation-based model in which we propose specific modes of action of chemotherapeutic agents on the autophagic flux and the corresponding strategies of modulation to enhance the response to chemotherapy. Our results point towards a promising therapeutic potential of the metabolic regulation of autophagy to overcome chemotherapy resistance by eliciting ICD.

Metabolites published new progress about Autophagosome. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Application In Synthesis of 1223001-51-1.

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