Heterocyclic Building Blocks-Naphthyridine

Li, Jian-Chun; Zhang, Zhi-Jun; Liu, Dan; Jiang, Ming-Yan; Li, Rong-Tao; Li, Hong-Mei published the artcile< Quinolizidine alkaloids from the roots of Sophora flavescens>, HPLC of Formula: 6882-68-4, the main research area is quinolizidine alkaloid isolation Sophora flavescens cancer inflammation; Sophora; Sophora flavescens Alt; anti-inflammation; cytotoxicity; quinolizidine alkaloids.

Seventeen quinolizidine alkaloids, including a new matrine-type one, sophcence A, were isolated from the roots of Sophora flavescens Alt. The structure of compound was elucidated by means of 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The NMR data of (-)-Δ7-dehydrosophoramine () and oxy-N-methylcytisine () were reported for the first time. In addition, (+)-sophoranol () exhibited moderate inhibition on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 22.14 μM, while lupanine () was found to inhibit the growth of human glioma stem cells GSC-3# at 20 μg/mL.

Natural Product Researchpublished new progress about Alkaloids Role: NPO (Natural Product Occurrence), PAC (Pharmacological Activity), PUR (Purification or Recovery), THU (Therapeutic Use), BIOL (Biological Study), OCCU (Occurrence), PREP (Preparation), USES (Uses). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, HPLC of Formula: 6882-68-4.

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>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, 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 Therapeuticspublished new progress about Antitumor agents. 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

Zhao, Wu-li; Xing, Yan; Ye, Cheng; Qiu, Yu-han; Li, Yi; Liu, Xiu-jun; Wang, Meng-yan; Bi, Chong-wen; Song, Dan-qing; Shao, Rong-guang published the artcile< The novel sophoridine derivate IMB-HDC induced lessened phosphorylation of STAT5a at 694 and 780 and promoted DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation>, Category: naphthyridine, the main research area is cancer cell apoptosis sophoridine derivate STAT5a DNA breakage; DNA breakage; STAT5a; anticancer; nuclear location; shuttle.

Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. Meanwhile, IMB-HDC that induced the diminished expression of STAT5a target gene contributes to proliferation and leads to apoptosis. More importantly, we give the first evidence that promoting the effect of Tyr694 phosphorylation on nuclear location and subsequent STAT5a target gene transcription depends on Ser780 increased or unchanged phosphorylation and was not correlated with Ser726 phosphorylation.

Acta Pharmacologica Sinicapublished new progress about Animal gene, Bcl-2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Shen, Chen; Chen, Jin Hong; Lee, Youngyi; Hassan, Mehedi Md.; Kim, Su Jin; Choi, Eun Young; Hong, Seong-Tshool; Park, Byung-Hyun; Park, Ji Hyun published the artcile< mTOR- and SGK-mediated connexin 43 expression participates in lipopolysaccharide-stimulated macrophage>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is mTOR SGK connexin43 peritoneal macrophage bacterial peritonitis.

Connexin 43 (Cx43) deficiency was found to increase mortality in a mouse model of bacterial peritonitis, and Cx43 is upregulated in macrophages by LPS treatment. In this study, we characterized a novel signaling pathway for LPS-induced Cx43 expression in RAW264.7 cells and thioglycolate-elicited peritoneal macrophages (TGEMs). LPS alone or LPS-containing conditioned medium (CM) upregulated Cx43. Overexpression or silencing of Cx43 led to the enhancement or inhibition, resp., of CM-induced TGEM migration. This response involved the inducible NO synthase (iNOS)/focal adhesion kinase (FAK)/Src pathways. Moreover, CM-induced migration was compromised in TGEMs from Cx43+/2 mice compared with TGEMs from Cx43+/+ littermates. Cx43 was upregulated by a serum/glucocorticoid-regulated kinase 1 (SGK) activator and downregulated, along with inhibition of CM-induced TGEM migration, by knockdown of the SGK gene or blockade of the SGK pathway. LPS-induced SGK activation was abrogated by Torin2, whereas LPS-induced Cx43 was downregulated by both Torin2 and rapamycin. Anal. of the effects of FK506 and methylprednisolone, common immunosuppressive agents following organ transplantation, suggested a link between these immunosuppressive drugs and impaired macrophage migration via the Cx43/iNOS/Src/FAK pathway. In a model of Escherichia coli infectious peritonitis, GSK650349-, an SGK inhibitor, or Torin2-treated mice showed less accumulation of F4/80+CD11b+ macrophages in the peritoneal cavity, with a delay in the elimination of bacteria. Furthermore, following pretreatment with Gap19, a selective Cx43 hemichannel blocker, the survival of model mice was significantly reduced. Taken together, our study suggested that Cx43 in macrophages was associated with macrophage migration, an important immune process in host defense to infection.

Journal of Immunologypublished new progress about Adhesion G protein-coupled receptor E1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Hussain, Azhar R.; Al-Romaizan, Maha; Ahmed, Maqbool; Thangavel, Saravanan; Al-Dayel, Fouad; Beg, Shaham; Uddin, Shahab; Siraj, Abdul K.; Al-Kuraya, Khawla S. published the artcile< Dual targeting of mTOR activity with Torin2 potentiates anticancer effects of cisplatin in epithelial ovarian cancer>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is Torin2 cisplatin antitumor mTOR signaling epithelial ovarian cancer.

Mammalian target of rapamycin (mTOR) and phosphatidylinositol 3-kinase (PI3K) are two key components of PI3K/Akt/mTOR signaling pathway. Dysregulation of these pathways have been found in many cancers, including epithelial ovarian cancer (EOC), however, the role of mTOR has not been fully elucidated in Middle Eastern EOC. Therefore, we investigated the activation of mTOR complexes (mTORC1 and mTORC2) in a cohort of 156 EOC from Saudi Arabia by immunohistochem. in a tissue microarray format. mTORC1 and mTORC2 were found to be activated in 55 of 146 (37.7%) and 63 of 140 (45%) of EOC samples, resp. mTORC1 was significantly associated with mTORC2 (p < 0.0001) activation and both mTOR complexes were significantly associated with p-AKT (p = 0.0205 and 0.0298) and p-P70S6 (p < 0.0001 and 0.0035), resp. Interestingly, mTOR activation incurred a poor progression-free survival (PFS) (p = 0.0188) in EOC. Next, the in vitro effect of inactivation of mTOR complexes was evaluated using a second-generation mTOR inhibitor, Torin2, on a panel of EOC cell lines. Torin2 treatment decreased cell viability and induced apoptosis in a dose-dependent manner via inactivation of mTORC1 and mTORC2 and their downstream targets in EOC cell lines. Furthermore, treatment of EOC cells with a subtoxic dose of Torin2 potentiated a cisplatin-induced apoptotic response in EOC cell lines. Finally, we studied the in vivo effect of a combination of Torin2 and cisplatin and found that this combination synergistically inhibited tumor growth in nude mice. These studies highlight the importance of targeting the mTOR survival pathway and suggest that cotreatment with cisplatin and Torin2 may be beneficial for the management of EOC. Molecular Medicine (Manhasset, NY, United States)published new progress about Antitumor agents. 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

Yang, Diane; Patel, Sanjeet; Szlachcic, Wojciech J.; Chmielowiec, Jolanta; Scaduto, Diane; Putluri, Nagireddy; Sreekumar, Arun; Suliburk, James; Metzker, Michael; Balasubramanyam, Ashok; Borowiak, Malgorzata published the artcile< Pancreatic differentiation of stem cells reveals pathogenesis of a syndrome of ketosis-prone diabetes>, Synthetic Route of 1223001-51-1, the main research area is human ketosis prone diabetes stem cell pancreatic differentiation PDX1.

Genetic anal. of an adult patient with an unusual course of ketosis-prone diabetes (KPD) and lacking islet autoantibodies demonstrated a nucleotide variant in the 5′-untranslated region (UTR) of PDX1, a β-cell development gene. When differentiated to the pancreatic lineage, his induced pluripotent stem cells stalled at the definitive endoderm (DE) stage. Metabolomics anal. of the cells revealed that this was associated with leucine hypersensitivity during transition fromthe DE to the pancreatic progenitor (PP) stage, and RNA sequencing showed that defects in leucine- sensitive mTOR pathways contribute to the differentiation deficiency. CRISPR/Cas9 manipulation of the PDX1 variant demonstrated that it is necessary and sufficient to confer leucine sensitivity and the differentiation block, likely due to disruption of binding of the transcriptional regulator NFY to the PDX1 5′-UTR, leading to decreased PDX1 expression at the early PP stage. Thus, the combination of an underlying defect in leucine catabolism characteristic of KPD with a functionally relevant heterozygous variant in a critical β-cell gene that confers increased leucine sensitivity and inhibits endocrine cell differentiation resulted in the phenotype of late-onset β-cell failure in this patient. We define themol. pathogenesis of a diabetes syndrome and demonstrate the power of multiomics anal. of patient-specific stemcells for clin. discovery.

Diabetespublished new progress about 5′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Rizvi, Syed Arif Hussain; Ling, Siquan; Tian, Fajun; Liu, Jiali; Zeng, Xinnian published the artcile< Interference mechanism of Sophora alopecuroides L. alkaloids extract on host finding and selection of the Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera: Psyllidae)>, SDS of cas: 6882-68-4, the main research area is Sophora Diaphorina Murraya seedling alkaloid host selection; Alkaloids; Behavioral effect; Botanical pesticides; Diaphorina citri; Host selection; Sophora alopecuroides.

Manipulating insect behavior through the deployment of semiochems. offers a promising opportunity for protecting crops in a sustainable manner. Therefore, there is still a significant opportunity for the development of natural crop protectants as eco-friendly tools in pest management. In this context, the aim of the current investigation is to find a novel prophylactic against the Asian citrus psyllid (ACP) and to gain a better understanding of the host-finding and selection ability of the ACP towards Murraya paniculata seedlings treated with Sophora alopecuroides alkaloids extract (SAAE). Our results indicate that foliar application of SAAE influences the psyllid host-finding and selection process. The behavioral assay with M. paniculata seedlings treated with 15 and 30 mg/mL of SAAE, with masked visual cues, revealed that only 6.6 and 10.4% psyllids were able to locate the host in the vials. The results also indicate that citrus psyllids mainly rely on both visual and olfaction in host-finding and selection. In choice settling experiments, psyllids settled almost completely on control seedlings rather than on seedlings treated with SAAE at a concentration of 30 mg/mL. Chem. analyses of the alkaloids extract revealed the presence of sophocarpine (33.90%), sophoridine (6.23%), anagyrine (2.77%), matrine (2.38%), lupanine (1.68%) aphylline (0.89%), and sophoramine (0.75%). In further behavioral bioassays with the dominant alkaloids sophocarpine and sophoridine, the alkaloids repelled ACP at higher concentrations of 50 and 70 mg/mL as compared to SAAE. Furthermore, the 50 mg/mL (1:1, volume/volume) combination of sophocarpine and sophoridine displayed a synergistic effect and showed the maximum behavioral effect as compared to the individual alkaloid. Based on our results, SAAE makes M. paniculata seedlings unattractive to the psyllids, and therefore, alkaloids could be used in reducing the colonization of citrus plants, subsequently curtailing HLB infection.

Environmental Science and Pollution Researchpublished new progress about Agrochemical sprays. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, SDS of cas: 6882-68-4.

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>, Electric Literature of 6882-68-4, 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 Medicinepublished new progress about Aging, animal. 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

Yu, Pan; Cao, Weiya; Yang, Shilong; Wang, Yuan; Xia, Aixin; Tan, Xinlan; Wang, Luyi published the artcile< Design, synthesis and antitumor evaluation of novel quinazoline analogs in hepatocellular carcinoma cell>, HPLC of Formula: 1223001-51-1, the main research area is quinazoline preparation antitumor activity mol docking protein kinase inhibitor.

In this paper, five quinazoline analogs I (R = Cl, 1H-indol-5-yl, 4-chlorophenyl, pyridin-3-yl, 4-aminophenyl) were preliminary designed through scaffold shopping from mTOR inhibitors and synthesized in four steps. Five compounds I exhibited potent antitumor activity against the HepG2 cell line by MTT assay. Compound I (R = 1H-indol-5-yl) (II) (IC50 = 4.06μM) was found as the most potent analog and showed better antiproliferative ability than sorafenib (IC50 = 6.14μM). The result of the wound healing assay and transwell migration assay indicated II strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. The underlying mechanism of its cytotoxicity was also investigated and the results of western blotting confirmed that compound II exposure could block the cell cycle, promote apoptosis and inhibit AKT and mTOR phosphorylation in HepG2 cells. Mol. docking further supported that compound II showed a high affinity to mTOR kinase. The results favored rational design intention and hinted that the new quinazolines I might be helpful in the further explorations of potent agents.

Journal of Molecular Structurepublished new progress about Antitumor agents. 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

Tamir, Tigist Y.; Bowman, Brittany M.; Agajanian, Megan J.; Goldfarb, Dennis; Schrank, Travis P.; Stohrer, Trent; Hale, Andrew E.; Siesser, Priscila F.; Weir, Seth J.; Murphy, Ryan M.; LaPak, Kyle M.; Weissman, Bernard E.; Moorman, Nathaniel J.; Ben Major, M. published the artcile< Gain-of-function genetic screen of the kinome reveals BRSK2 as an inhibitor of the NRF2 transcription factor>, Quality Control of 1223001-51-1, the main research area is nuclear erythroid transcription factor brain specific kinase human disease; AMPK; BRSK1; BRSK2; Functional genomics; Kinase; NRF2; Oxidative stress response; Phosphoproteomics; mTOR.

Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, but conversely NRF2 activity diminishes with age and in neurodegenerative and metabolic disorders. Although NRF2-activating drugs are clin. beneficial, NRF2 inhibitors do not yet exist. Here, we describe use of a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the under-studied protein kinase brain-specific kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives 5′-AMP-activated protein kinase α2 (AMPK) signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppresses ribosome-RNA complexes, global protein synthesis and NRF2 protein levels. Collectively, our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis might prove useful for therapeutically targeting NRF2 in human disease.

Journal of Cell Sciencepublished new progress about Activating transcription factor 3 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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