Heterocyclic Building Blocks-Naphthyridine

Hu, Chunhui; Gan, Xuehui; Jia, Qiangqiang; Gao, Pan; Du, Tao; Zhang, Fabin published the artcile< Optimization of supercritical-CO2 extraction and pharmacokinetics in SD rats of alkaloids form Sophora moorcroftiana seed>, Category: naphthyridine, the main research area is Sophora alkaloid carbon dioxide extraction pharmacokinetics optimization.

The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box-Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatog. coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78-200.00 ng/mL, R2 > 0.99, and the sample recovery is 99-113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clin. applications.

Scientific Reports published new progress about Alkalinization. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Category: naphthyridine.

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

Luo, Jia; Pi, Guocheng; Xiao, He; Ye, Yunfei; Li, Qing; Zhao, Lianhua; Huang, Huan; Luo, Hong; Zhang, Qin; Wang, Dong; Wang, Ge published the artcile< Torin2 enhances the radiosensitivity of MCF-7 breast cancer cells by downregulating the mTOR signaling pathway and ATM phosphorylation>, Electric Literature of 1223001-51-1, the main research area is X ray Torin mTOR inhibitor radiosensitivity ATM breast cancer.

Radiotherapy has an important role in the comprehensive treatment of breast cancer. However, the clin. outcome of adjuvant radiotherapy may be limited due to intrinsic radioresistance, it is necessary to explore efficient radiosensitization methods that improve the clin. outcome of patients undergoing radiotherapy. The present study aimed to investigate whether the novel mechanistic target of rapamycin (mTOR) inhibitor Torin2 enhances the radiosensitivity of MCF-7 breast cancer cells. A Cell Counting Kit-8 (CCK-8) assay was performed to measure the effect of Torin2 on cell proliferation, while clonogenic assays were employed to determine the effect of Torin2 in combination with radiation on the proliferation of MCF-7 cells. The effect of Torin2 and/or radiation on the cell cycle was analyzed using flow cytometry. Furthermore, the protein expression of components of the phosphatidylinositol 3-kinase/Akt/mTOR pathway, and the expression of proteins involved in DNA damage repair, was measured by western blot anal. The results demonstrated that Torin2 exhibited a higher potency in MCF-7 cells, while MDA-MB-231 cells were less sensitive to Torin2. Compared with irradiation alone, pretreatment with 20 nM Torin2 followed by irradiation resulted in an increased level of γ-H2A histone family member X. Radiation induced the activation of the Akt/mTOR signaling pathway and upregulated the expression of phosphorylated (p)-Akt473 and p-eukaryotic translation initiation factor 4E binding protein 1 (4EBP1)37/46. Notably, pretreatment with Torin2 attenuated the radiation-induced activation of the Akt/mTOR signaling pathway. In addition, Torin2 partially blocked the repair of double-strand breaks induced by radiation by reducing the activation of ataxia telangiectasia-mutated, and sensitized MCF-7 cells to radiation. In conclusion, administration of Torin2 prior to irradiation enhanced the radiotherapeutic effect on breast cancer cells in vitro, and these results may provide a foundation for the rational use of combined therapy with irradiation and Torin2 for breast cancer in clin. practice.

Molecular Medicine Reports published new progress about Cell cycle checkpoint. 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

Valenciano, Ana L.; Ramsey, Aaron C.; Santos, Webster L.; Mackey, Zachary B. published the artcile< Discovery and antiparasitic activity of AZ960 as a Trypanosoma brucei ERK8 inhibitor>, Product Details of C24H15F3N4O, the main research area is AZ960 trypanosomiasis trypanosomicide trypanosoma ERK8 inhibitor; AZ960; Extracellular-signal regulated kinase (ERK); High-throughput screening; Mitogen-activated protein kinase (MAPK); Trypanosoma brucei.

Human African trypanosomiasis (HAT) is a lethal, vector-borne disease caused by the parasite Trypanosoma brucei. Therapeutic strategies for this neglected tropical disease suffer from disadvantages such as toxicity, high cost, and emerging resistance. Therefore, new drugs with novel modes of action are needed. The authors screened cultured T. brucei against a focused kinase inhibitor library to identify promising bioactive compounds Among the ten hits identified from the phenotypic screen, AZ960 I emerged as the most promising compound with potent antiparasitic activity (IC50 = 120 nM) and was shown to be a selective inhibitor of an essential gene product, T. brucei extracellular signal-regulated kinase 8 (TbERK8). The authors report that AZ960 has a Ki of 1.25 μM for TbERK8 and demonstrate its utility in establishing TbERK8 as a potentially druggable target in T. brucei.

Bioorganic & Medicinal Chemistry published new progress about Chagas disease. 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

Hassett, Matthew R.; Sternberg, Anna R.; Roepe, Paul D. published the artcile< Inhibition of Human Class I vs Class III Phosphatidylinositol 3'-Kinases>, Quality Control of 1223001-51-1, the main research area is inhibition class I III isoenzyme phosphatidylinositol kinase PI3K.

Most investigations of phosphatidylinositol 3′-kinase (PI3K) drug inhibition have been via assays based on ADP appearance or ATP consumption (e.g. Liu, Q. et al. (2011) J. Med. Chem. 54, 1473-1480). However, at least some PI3K isoforms show basal ATPase activity in the absence of PI lipid substrate(s), which may complicate quantification of drug potency, isoform specificity of some drugs, and synergy for drug combinations. In this study, we probe the class I vs. class III isoform specificity of a selected set of phosphatidylinositol 3′-kinase (PI3K) inhibitors using a simple, inexpensive, semi high-throughput assay that quantifies production of phosphatidylinositol 3′-phosphate (PI3P) from phosphatidylinositol (PI). Results are compared to previous data largely generated using ATPase activity assays. Good agreement between EC50 values computed via ATPase assays vs. the reported PI3P formation assay is found for most drugs, but with a few exceptions. Also, for the first time, drug inhibition of class I vs. class III enzymes is compared side-by-side with the same assay for the important class I specific inhibitors GSK2126458 (“”Omipalisib””) and NVP-BGT226 (“”BGT226″”) currently in clin. development for advanced solid tumors.

Biochemistry published new progress about Enzyme inhibition kinetics. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.

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

Hau, Andrew M.; Nakasaki, Manando; Nakashima, Kazufumi; Krish, Goutam; Hansel, Donna E. published the artcile< Differential mTOR pathway profiles in bladder cancer cell line subtypes to predict sensitivity to mTOR inhibition>, Formula: C24H15F3N4O, the main research area is mtor pathway bladder cancer cell line subtype inhibition; Basal; Bladder cancer; Cell lines; Luminal; mTOR; mTOR inhibitor.

Mol. classification of bladder cancer has been increasingly proposed as a potential tool to predict clin. outcomes and responses to chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal (“”non-type””) mol. subtypes. Protein and mRNA expression of mTOR signaling components from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype (T24 and J82) bladder cancer cell line subtypes were determined by Western blot and database mining anal. of the Cancer Cell Line Encyclopedia. Cell viability following treatment with either, Torin-2 or KU-0063794, 2 dual mTOR complex 1/2 inhibitors, was determined by MTT assay. Immunoblot anal. of cells treated with Torin-2 or KU-0063794 was performed to determine the effects of mTOR inhibition on expression and phosphorylation status of mTOR signaling components, Akt, 4E-BP1, and ribosomal protein S6. Mol. subtypes of bladder cancer cell lines each exhibited a distinct pattern of expression of mTOR-associated genes and baseline phosphorylation level of Akt and 4E-BP1. Cells with low levels of Akt Ser-473 phosphorylation were more resistant to the cytotoxic effects of mTOR inhibition with Torin-2, but not KU-0063794. Exposure to Torin-2 and KU-0063794 both potently and rapidly inhibited phosphorylation of Akt Ser-473 and Thr-308, and 4E-BP1 T37/46 in cell lines that included basal and nontype subtypes. Differential gene expression and protein activity associated with mTOR signaling is observed among bladder cancer cell lines stratified into basal, luminal, and nontype subtypes. Urothelial carcinomas characterized by high baseline Akt Ser-473 phosphorylation may be best suited for targeted mTOR therapies.

Urologic Oncology: Seminars and Original Investigations 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

Li, Wenxuan; Deng, Lijuan; Lei, Yuhe; Liu, Junshan published the artcile< Network-pharmacology and molecular docking-based investigation of mechanism of Sophora flavescens on cancer and inflammation>, Category: naphthyridine, the main research area is Sophora network pharmacol mol docking.

Objective: In order to explore the systematical regulatory mechanism of Kushen (Sophora flavescens, SF) on inflammation and cancer, we analyzed inter-mol. interactions between herbal ingredients of SF and human inflammation and cancer through network-pharmacol. and mol. docking-based approaches. Methods: Firstly, ingredients and potential targets were obtained from Traditional Chinese Medicine Systems Pharmacol. Database and Anal. Platform, GeneCards database, Therapeutic Targets Database and Online Mendelian Inheritance in Man database. Then, protein-protein interaction network and medicine-ingredient-target-disease network were established and analyzed via STRING and Cytoscape. Surflex-dock was performed by SybylX-2.0. Finally, functional enrichment and pathway enrichment were achieved by Gene Ontol. database and Kyoto Encyclopedia of Genes and Genomes database. Results: The results showed that 113 components of SF and 53 potential targets were related in the study. Conclusions: The study predicted the mechanism of SF on cancer and inflammation. According to the results, we suggest that the ingredients of SF effect on DNA bingding and transcription in nuclear receptors-like JUN, MYC, RELA, NCOA, PPARG. the receptors trigger several pathways including NF-κB pathway, the Bcl-2/Bax pathway and others. Eventually, it regulats inflammatory factors and cell proliferation, senescence and apoptosis.

TMR Modern Herbal Medicine published new progress about Aging, animal. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Category: naphthyridine.

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

Wu, H.; Hu, C.; Wang, A.; Weisberg, E. L.; Chen, Y.; Yun, C.-H.; Wang, W.; Liu, Y.; Liu, X.; Tian, B.; Wang, J.; Zhao, Z.; Liang, Y.; Li, B.; Wang, L.; Wang, B.; Chen, C.; Buhrlage, S. J.; Qi, Z.; Zou, F.; Nonami, A.; Li, Y.; Fernandes, S. M.; Adamia, S.; Stone, R. M.; Galinsky, I. A.; Wang, X.; Yang, G.; Griffin, J. D.; Brown, J. R.; Eck, M. J.; Liu, J.; Gray, N. S.; Liu, Q. published the artcile< Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia>, Synthetic Route of 1223001-51-1, the main research area is lymphoma leukemia Bruton tyrosine kinase MNK dual inhibitor.

Bruton’s tyrosine kinase (BTK) kinase is a member of the TEC kinase family and is a key regulator of the B-cell receptor (BCR)-mediated signaling pathway. It is important for B-cell maturation, proliferation, survival and metastasis. Pharmacol. inhibition of BTK is clin. effective against a variety of B-cell malignances, such as mantle cell lymphoma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and activated B-cell-diffuse large B-cell lymphoma. MNK kinase is one of the key downstream regulators in the RAF-MEK-ERK signaling pathway and controls protein synthesis via regulating the activity of eIF4E. Inhibition of MNK activity has been observed to moderately inhibit the proliferation of AML cells. Through a structure-based drug-design approach, we have discovered a selective and potent BTK/MNK dual kinase inhibitor (QL-X-138), which exhibits covalent binding to BTK and noncovalent binding to MNK. Compared with the BTK kinase inhibitor (PCI-32765) and the MNK kinase inhibitor (cercosporamide), QL-X-138 enhanced the antiproliferative efficacies in vitro against a variety of B-cell cancer cell lines, as well as AML and CLL primary patient cells, which respond moderately to BTK inhibitor in vitro. The agent can effectively arrest the growth of lymphoma and leukemia cells at the G0-G1 stage and can induce strong apoptotic cell death. These primary results demonstrate that simultaneous inhibition of BTK and MNK kinase activity might be a new therapeutic strategy for B-cell malignances.

Leukemia published new progress about Acute myeloid leukemia. 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

Chernoryzh, Ya. Yu.; Fedorova, N. E.; Yurlov, K. I.; Simonov, R. A.; Kornev, A. B.; Karpov, D. S.; Zakirova, N. F.; Ivanov, A. V.; Kushch, A. A.; Gintsburg, A. L. published the artcile< Resistance of THP-1 Leukemia Cells Infected with Cytomegalovirus to Anti-tumor Antibiotic Doxorubicin and Restoration of the Sensitivity by Inhibitors of the PI3K/AKT/mTOR Molecular Pathway>, Computed Properties of 1223001-51-1, the main research area is doxorubicin anticancer agent antibiotic PI3K cytomegalovirus leukemia.

Abstract: Results obtained showed that infection with HCMV prevented the death of THP-1 cells treated with DOX in both active and latent forms of infection. In the presence of mTOR inhibitors (rapamycin and Torin2), the sensitivity of the infected cells to DOX was restored. Rapamycin inhibited the expression of the HCMV protein IE1-p72 and increased sensitivity to DOX. Mol. targets for the creation of new drugs for the treatment of leukemia in patients infected with HCMV were determined

Doklady Biochemistry and Biophysics published new progress about Antibiotics Role: THU (Therapeutic Use), BIOL (Biological Study), USES (Uses). 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

Hou, Zhifei; Sun, Guoxiang; Guo, Yong; Yang, Fangliang; Gong, Dandan published the artcile< Capillary electrophoresis fingerprints combined with Linear Quantitative Profiling Method to monitor the quality consistency and predict the antioxidant activity of Alkaloids of Sophora flavescens>, Safety of (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one, the main research area is Sophora antioxidant alkaloid determination capillary electrophoresis; Alkaloids of Sophora flavescens; Capillary electrophoresis fingerprints; Fingerprint-efficacy relationship; Quality consistency; The total antioxidant capacity.

Alkaloids of Sophora flavescens (ASF) has various pharmacol. effects, and it is widely used in clin. practice. The aim of this research was to develop an environmentally friendly methodol. that enables not only identification but also the quality consistency assessment of Alkaloids of Sophora flavescens. A background electrolyte composed of 50 mmol/L sodium tetraborate solution, 500 mmol/L boric acid and 1.2 mmol/L citric acid was used to conduct the fingerprint anal. coupled with quant. determination of three components. Linear quant. profiling method was used for comprehensive quality discrimination of the test samples from both qual. and quant. perspectives, and the 27 batches of samples were well differentiated. In addition, the fingerprint-efficacy relationship between chem. components and antioxidant activity in vitro was established using partial least squares regression model, which provided important medicinal efficacy information for quality control.

Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences published new progress about Alkaloids Role: ANT (Analyte), THU (Therapeutic Use), ANST (Analytical Study), BIOL (Biological Study), USES (Uses). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Safety of (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one.

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

Xu, Fei; Li, Xin; Yan, Lili; Yuan, Na; Fang, Yixuan; Cao, Yan; Xu, Li; Zhang, Xiaoying; Xu, Lan; Ge, Chaorong; An, Ni; Jiang, Gaoyue; Xie, Jialing; Zhang, Han; Jiang, Jiayi; Li, Xiaotian; Yao, Lei; Zhang, Suping; Zhou, Daohong; Wang, Jianrong published the artcile< Autophagy promotes the repair of radiation-induced DNA damage in bone marrow hematopoietic cells via enhanced STAT3 signaling>, Product Details of C24H15F3N4O, the main research area is gamma radiation autophagy DNA damage BM hematopoietic cell.

Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the mol. mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7. The autophagic regulation of STAT3 activation is likely mediated by induction of KAP1 degradation, because we showed that KAP1 directly interacted with STAT3 in the cytoplasm and knockdown of KAP1 increased the phosphorylation and nuclear translocation of STAT3. Subsequently, activated STAT3 transcriptionally upregulated the expression of BRCA1, which increased the ability of BM-MNCs to repair radiation-induced DNA damage. This novel finding that activation of autophagy can promote DNA damage repair in BM-MNCs via the ATG-KAP1-STAT3-BRCA1 pathway suggests that autophagy plays an important role in maintaining genomic integrity of BM-MNCs and its activation may confer protection of BM-MNCs against radiationinduced genotoxic stress.

Radiation Research published new progress about Autophagy. 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