Tag: M.W=400-600

Garcia, Gustavo; Sharma, Arun; Ramaiah, Arunachalam; Sen, Chandani; Purkayastha, Arunima; Kohn, Donald B.; Parcells, Mark S.; Beck, Sebastian; Kim, Heeyoung; Bakowski, Malina A.; Kirkpatrick, Melanie G.; Riva, Laura; Wolff, Karen C.; Han, Brandon; Yuen, Constance; Ulmert, David; Purbey, Prabhat K.; Scumpia, Phillip; Beutler, Nathan; Rogers, Thomas F.; Chatterjee, Arnab K.; Gabriel, Gulsah; Bartenschlager, Ralf; Gomperts, Brigitte; Svendsen, Clive N.; Betz, Ulrich A. K.; Damoiseaux, Robert D.; Arumugaswami, Vaithilingaraja published the artcile< Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication>, COA of Formula: C24H15F3N4O, the main research area is human covid antiviral drug screening DNA damage response inhibitor; ATR kinase; COVID-19; DNA-damage response pathway; SARS-CoV-2; berzosertib; high-throughput screen; mTOR-PI3K-AKT pathway; nucleoside analogs; protein kinase inhibitors.

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-mol. library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clin. trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

Cell Reports published new progress about Antiviral 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

Tavares, Catarina; Eloy, Catarina; Melo, Miguel; da Rocha, Adriana Gaspar; Pestana, Ana; Batista, Rui; Ferreira, Luciana Bueno; Rios, Elisabete; Simoes, Manuel Sobrinho; Soares, Paula published the artcile< mTOR pathway in papillary thyroid carcinoma: different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression>, Electric Literature of 1223001-51-1, the main research area is PTC mTORC tumor behavior SLCA mTOR pathway; mTOR; sodium iodide symporter (NIS)/SLC5A5; thyroid cancer.

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathol. features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochem. for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was pos. correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ∼6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.

International Journal of Molecular Sciences published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (BRAF). 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

Malik, Nasir; Manickam, Rohini; Bachani, Muznabanu; Steiner, Joseph P. published the artcile< A strategy to identify compounds that affect cell growth and survival in cultured mammalian cells at low-to-moderate throughput>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is growth cultured mammalian neural stem cell.

Cytotoxicity is a critical parameter that needs to be quantified when studying drugs that may have therapeutic benefits. Because of this, many drug screening assays utilize cytotoxicity as one of the critical characteristics to be profiled for individual compounds Cells in culture are a useful model to assess cytotoxicity before proceeding to follow up on promising lead compounds in more costly and labor-intensive animal models. We describe a strategy to identify compounds that affect cell growth in a tdTomato expressing human neural stem cells (NSC) line. The strategy uses two complementary assays to assess cell number One assay works via the reduction of 3-(4,5-dimethylthizol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) to formazan as a proxy for cell number and the other directly counts the tdTomato expressing NSCs. The two assays can be performed simultaneously in a single experiment and are not labor intensive, rapid, and inexpensive. The strategy described in this demonstration tested 57 compounds in an exploratory primary screen for toxicity in a 96-well plate format. Three of the hits were characterized further in a six-point dose response using the same assay set-up as the primary screen. In addition to providing excellent corroboration for toxicity, comparison of results from the two assays may be effective in identifying compounds affecting other aspects of cell growth.

Journal of Visualized Experiments published new progress about Cell enlargement. 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

Feehan, Robert P.; Shantz, Lisa M. published the artcile< Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation>, Application of C24H15F3N4O, the main research area is UVB radiation FOXO3a mTORC2 cell survival skin cancer; Apoptosis; Cancer chemoprevention; FOXO; Keratinocyte; Mammalian target of rapamycin (mTOR); UVB.

Exposure to UV-B (UVB) irradiation, the principal cause of non-melanoma skin cancer (NMSC), activates both the rapamycin-sensitive mammalian target of rapamycin complex 1 (mTORC1) and the rapamycin-resistant mTORC2. We have previously reported that UVB-induced keratinocyte survival is dependent on mTORC2, though the specific mechanism is not well understood. FOXO3a is an important transcription factor involved in regulating cell survival. The activity of FOXO3a is reduced as a result of protein kinase B (AKT/PKB) activation, which is downstream of mTORC2; however, the specific function of FOXO3a during UVB-induced apoptosis is unclear. In this study, we establish that in cells with wild-type mTORC2 activity, FOXO3a is quickly phosphorylated in response to UVB and sequestered in the cytoplasm. In contrast, loss of mTORC2 causes FOXO3a to be localized to the nucleus and sensitizes cells to UVB-induced apoptosis. Furthermore, this sensitization is rescued by knockdown of FOXO3a. Taken together, these studies provide strong evidence that inhibition of mTORC2 enhances UVB-induced apoptosis in a FOXO3a-dependent manner, and suggest that FOXO3a activation by mTORC2 inhibitors may be a valuable chemopreventive target in NMSC.

Cellular Signalling published new progress about Apoptosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Application of C24H15F3N4O.

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

Zhang, Lei; Yang, Xingxing; Liu, Juanjuan; Luo, Yan; Li, Zhiyuan; Ji, Xinmiao; Wang, Wenchao; Zhang, Xin published the artcile< 1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of mTOR inhibitors in CNE-2Z cells>, COA of Formula: C24H15F3N4O, the main research area is Torin2 magnetic field anticancer agent Akt mTOR nasopharyngeal carcinoma.

Static magnetic field (SMF) has been known to affect cell proliferation in a cell-type-dependent manner, while the mechanism still remains unclear. We found that 1 T moderate intensity SMF inhibits cell proliferation of nasopharyngeal carcinoma CNE-2Z cells and the Akt/mTOR signaling pathway, which is upregulated in many cancers. mTOR inhibitors are potential chemodrugs, but their clin. effects are limited by the feedback reactivation of other signaling components such as EGFR and Akt. We showed that 1 T SMF increases the antitumor efficacy of mTOR inhibitor Torin 2. In addition, 1 T SMF increases the inhibition efficiency on mTOR substrates phosphorylation and represses the mTOR inhibitor-induced feedback reactivation of EGFR and Akt. Our study not only demonstrates that mTOR/Akt pathway is one of the mol. targets of SMFs in cells, but also reveals the clin. potentials of combinations of mTOR inhibitors and SMFs in cancer treatment.

Science Bulletin 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

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

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

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

Liu, Yanlin; Duan, Xiaoli; Zhao, Xiaodi; Ding, Wenlong; Wang, Yaowei; Xiong, Yan published the artcile< Diverse nitrogen signals activate convergent ROP2-TOR signaling in Arabidopsis>, SDS of cas: 1223001-51-1, the main research area is diverse nitrogen signal ROP2TOR Arabidopsis; ROP2; TOR; amino acids; cell proliferation; inorganic nitrogen; leaf primordium.

The evolutionarily conserved target-of-rapamycin (TOR) kinase coordinates cellular and organismal growth in all eukaryotes. Amino acids (AAs) are key upstream signals for mammalian TOR activation, but how nitrogen-related nutrients regulate TOR signaling in plants is poorly understood. Here, we discovered that, independent of nitrogen assimilation, nitrate and ammonium function as primary nitrogen signals to activate TOR in the Arabidopsis leaf primordium. We further identified that a total of 15 proteinogenic AAs are also able to activate TOR, and the first AAs generated from plant specific nitrogen assimilation (glutamine), sulfur assimilation (cysteine), and glycolate cycle (glycine), exhibit the highest potency. Interestingly, nitrate, ammonium, and glutamine all activate the small GTPase Rho-related protein from plants 2 (ROP2), and constitutively active ROP2 restores TOR activation under nitrogen-starvation conditions. Our findings suggest that specific evolutionary adaptations of the nitrogen-TOR signaling pathway occurred in plant lineages, and ROP2 can integrate diverse nitrogen and hormone signals for plant TOR activation.

Developmental Cell published new progress about Amino acids 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