Category: naphthyridine

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

Zhao, Zhongwei; Zhang, Dengke; Wu, Fazong; Tu, Jianfei; Song, Jingjing; Xu, Min; Ji, Jiansong published the artcile< Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression>, Related Products of 6882-68-4, the main research area is hepatocellular carcinoma growth sophoridine lenvatinib RAS MEK ERK VEGFR2; VEGFR2; hepatocellular carcinoma; lenvatinib resistance; sophoridine.

This study aims to investigate the underlying mechanism of lenvatinib resistance and explore the potential drug to improve the treatment for lenvatinib-resistant (LR) HCC. Here, we developed two human LR HCC cell lines by culturing with long-term exposure to lenvatinib. Results showed that the vascular endothelial growth factor receptors (VEGFR)2 expression and its downstream RAS/MEK/ERK signalling were obviously up-regulated in LR HCC cells, whereas the expression of VEGFR1, VEGFR3, FGFR1-4 and PDGFRα/β showed no difference. Furthermore, ETS-1 was identified to be responsible for VEGFR2 mediated lenvatinib resistance. The cell models were further used to explore the potential strategies for restoration of sensitivity of lenvatinib. Sophoridine, an alkaloid extraction, inhibited the proliferation, colony formation, cell migration and increased apoptosis of LR HCC cells. In vivo and in vitro results showed Sophoridine could further sensitize the therapeutic of lenvatinib against LR HCC. Mechanism studies revealed that Sophoridine decreased ETS-1 expression to down-regulate VEGFR2 expression along with downstream RAS/MEK/ERK axis in LR HCC cells. Hence, our study revealed that up-regulated VEGFR2 expression could be a predicator of the resistance of lenvatinib treatment against HCC and provided a potential candidate to restore the sensitivity of lenvatinib for HCC treatment.

Journal of Cellular and Molecular Medicine published new progress about Angiogenesis. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Related Products of 6882-68-4.

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

ur Rashid, Haroon; Rasool, Shagufta; Ali, Yousaf; Khan, Kamin; Martines, Marco Antonio Utrera published the artcile< Anti-cancer potential of sophoridine and its derivatives: Recent progress and future perspectives>, Recommanded Product: (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 review antitumor cancer sophoridine derivative; Alkaloid; Cancer; Phytochemical; Sophoridine; Topoisomerase I.

A review. Cancer is the second leading cause of mortality and has resulted in about 9.6 million deaths around the world in 2018. Cancer-caused deaths are expected to be 11.5 million by 2030 all over the world. Because of the fatal nature of cancer, substantial efforts are made all over the world to combat it. Phytoconstituents such as certain alkaloids, saponins, tannins, polyphenols, and terpenoids exhibit anticancer effects. Sophoridine is a tetracyclic quinolizidine alkaloid isolated from the stem and leaves of medicinal plants Sophora alopecuroides L., and Euchresta japonica Benth, and roots of Sophora alopecuroides Ait. Chinese Food and Drug Administration (CFDA) approved sophoridine as an antitumor agent in 2005. This review covers the antitumor activities of sophoridine and its derivatives The efficacy of sophoridine analogs is expressed with respect to their half-maximal inhibitory concentration (IC50 values). Structure-activity relationship (SAR) study for most of the sophoridine derivatives has been explained. Moreover, the current market of anticancer drugs and its expected growth are discussed. Prospects provide suggestions and clues for novel sophoridine-based anticancer agents with enhanced expected efficacy and min. toxicity.

Bioorganic Chemistry published new progress about Antitumor agents. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Recommanded Product: (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

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

Zhou, Wei; Wu, Jiarui; Zhang, Jingyuan; Liu, Xinkui; Guo, Siyu; Jia, ShanShan; Zhang, Xiaomeng; Zhu, Yingli; Wang, Miaomiao published the artcile< Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology>, Reference of 6882-68-4, the main research area is esophageal cancer Kushen injection pharmacol bioinformatics.

Compound Kushen injection (CKI), a medicine in widespread clin. use in China, has proven therapeutic effects on cancer. However, few mol. mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network anal. with network pharmacol. methods were undertaken to elucidate the underlying mol. mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clin. traits of ESCA were analyzed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacol. Mol. docking simulation was performed to recognize the binding activity of hub genes with CKI compounds The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the mol. mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.

Scientific Reports published new progress about Animal gene, c-erbB Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Reference of 6882-68-4.

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

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>, Electric Literature of 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 Research published 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, Electric Literature of 6882-68-4.

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

Chen, Mengchun; Jiang, Qi; Zhang, Mingyao; Chen, Sailing; Lou, Junsheng; Chen, Yijie; Wang, Fang; Wang, Rongyue published the artcile< Establishment of quantitative methodology for sophoridine analysis and determination of its pharmacokinetics and bioavailability in rat>, Reference of 6882-68-4, the main research area is sophoridine detection blood circulation pharmacokinetics bioavailability rat; Sophoridine; UPLC–MS/MS; bioavailability; pharmacokinetics; rat plasma.

The aim of this study is to develop a rapid and sensitive UPLC-MS/MS approach to determine the sophoridine (SOP) level in rat plasma and the pharmacokinetics of the substance. Sophoridine is used as an anti-inflammatory, anti-virus, anti-microbial, and anti-tumor alkaloid. It is essential to explore specific detection methods for the quant. anal. of SOP in the blood circulation. The rat plasma samples were prepared by one-step protein precipitation with acetonitrile. Subsequently, the samples were separated by chromatog. using a UPLC BEH C18 reversed-phase with an initial mobile phase of methanol and 0.1% formic acid aqueous solution The gradient elution was performed at a fixed flow rate of 0.4 mL/min, and multiple reaction monitoring (MRM) mode with an electrospray pos. ionization source was employed to detect the transitions of m/z 249.1 → 84.2 for SOP and m/z 264.3 → 69.8 for dendrobine (IS). The entire process required 3.5 min for each sample. A linear correlation was established over the range of 2-2000 ng/mL (r2≥0.9954) for SOP in rat plasma with a lower limit of quantification (LLOQ) at 2 ng/mL. The range of accuracy was tested between 94.90% and 100.80%, and the relative standard deviations (RSDs) toward both intra- and inter-day precision were <10%. Thus, this method was successfully applied to a pharmacokinetic study, and the subsequent results demonstrated a low absolute bioavailability of 2.32%. The present study established a reliable method that quantified the SOP concentration in rat plasma after administering a dose of 2 mg/kg i.v. or 20 mg/kg orally. Drug Development and Industrial Pharmacy published new progress about Alkaloids Role: ANT (Analyte), BSU (Biological Study, Unclassified), THU (Therapeutic Use), ANST (Analytical Study), BIOL (Biological Study), USES (Uses). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Reference of 6882-68-4.

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