Month: October 2022

Dai, Lin-Lin; Li, Dong-Dong; Zhao, Xiu-Mei; Zhi, Shuang; Shen, Hong-Sheng; Yang, Zi-Bo published the artcile< Synthesis and Antitumor Effect of Sophoridine Derivatives Bearing an Acyclic Aryloxy Phosphoramidate Mustard Functionality>, Computed Properties of 6882-68-4, the main research area is sophoridine aryloxy phosphoramidate mustard synthesis antitumor.

To elevate the potency of sophoridine, phosphoramidate mustard motif was incorporated to D-ring opened sophoridine scaffold. A series of acyclic aryloxy phosphoramidate mustard functionalized sophoridine derivatives were synthesized and screened for cytostatic activity in a range of different tumor cell lines (S180, H22, K562, MCF-7, SMMC-7721, and LoVo). All these compounds were shown to be more sensitive to S180 and H22 cells with IC50 values ranging from 2.10 to 7.21 μM. In addition, all targeted derivatives distinctly are more cytotoxic to cancer cells than normal cell L929. Compounds I (R = 3-ClC6H4, 4-BrC6H4, 1-naphthyl, 2-naphthyl) displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Their potential binding modes with DNA topoisomerase I complex have also been investigated.

Journal of Heterocyclic Chemistrypublished new progress about Antitumor agents. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Computed Properties of 6882-68-4.

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

Feehan, Robert P.; Nelson, Amanda M.; Shantz, Lisa M. published the artcile< Inhibition of mTORC2 enhances UVB-induced apoptosis in keratinocytes through a mechanism dependent on the FOXO3a transcriptional target NOXA but independent of TRAIL>, Product Details of C24H15F3N4O, the main research area is mTORC UVB keratinocyte apoptosis FOXOa transcription NOXA TRAIL; Apoptosis; NOXA; Non-melanoma skin cancer; TRAIL; UVB; mTOR.

The primary cause of non-melanoma skin cancer (NMSC) is UV B (UVB) radiation. We have shown previously that mTORC2 inhibition sensitizes keratinocytes to UVB-induced apoptosis mediated by the transcription factor FOXO3a. FOXO3a is a key regulator of apoptosis and a tumor suppressor in several cancer types. Activation of FOXO3a promotes apoptosis through the coordinated expression of a variety of target genes, including TRAIL and NOXA. We hypothesized that in the setting of mTORC2 inhibition, the UVB-induced expression of these factors would lead to apoptosis in a FOXO3a-dependent manner. Using spontaneously immortalized human keratinocytes (HaCaT cells), we observed that both TRAIL and NOXA expression increased in cells exposed to UVB and the TOR kinase inhibitor Torin 2. Similar to knockdown of FOXO3a, NOXA knockdown reversed the sensitization to UVB-induced apoptosis caused by mTORC2 inhibition. In contrast, loss of TRAIL by either knockdown or knockout actually enhanced expression of nuclear FOXO3a, which maintained apoptosis. These surprising results are not due to faulty death receptor signaling in HaCaT cells, as we found that the cells undergo extrinsic apoptosis in response to treatment with recombinant TRAIL. Even more striking, TRAIL knockout cells were sensitized to recombinant TRAIL-induced apoptosis compared to wild-type HaCaT cells, with the largest increase occurring in the presence of mTORC2 inhibition. Taken together, these studies provide strong evidence that mTORC2 controls UVB-induced apoptosis by regulating NOXA expression downstream of FOXO3a. Moreover, FOXO3a transcriptional activation by mTORC2 inhibitors may be a valuable target for prevention or therapy of NMSC, especially in cases with low endogenous TRAIL.

Cellular Signallingpublished new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (NOXA). 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

Hamed, Mohamed; Gladbach, Yvonne; Moeller, Steffen; Fischer, Sarah; Ernst, Mathias; Struckmann, Stephan; Storch, Alexander; Fuellen, Georg published the artcile< A workflow for the integrative transcriptomic description of molecular pathology and the suggestion of normalizing compounds, exemplified by Parkinson's disease>, Related Products of 1223001-51-1, the main research area is miRNA mRNA Parkinson disease mol pathol.

The volume of mol. observations on human diseases in public databases is continuously increasing at accelerating rates. A bottleneck is their computational integration into a coherent description, from which researchers may derive new well-founded hypotheses. Also, the need to integrate data from different technologies (genetics, coding and regulatory RNA, proteomics) emerged in order to identify biomarkers for early diagnosis and prognosis of complex diseases and therefore facilitating the development of novel treatment approaches. We propose here a workflow for the integrative transcriptomic description of the mol. pathol. in Parkinsons’s Disease (PD), including suggestions of compounds normalizing disease-induced transcriptional changes as a paradigmatic example. We integrated gene expression profiles, miRNA signatures, and publicly available regulatory databases to specify a partial model of the mol. pathophysiol. of PD. Six genetic driver elements (2 genes and 4 miRNAs) and several functional network modules that are associated with PD were identified. Functional modules were assessed for their statistical significance, cellular functional homogeneity, literature evidence, and normalizing small mols. In summary, our workflow for the joint regulatory anal. of coding and non-coding RNA, has the potential to yield clin. as well as biol. relevant information, as demonstrated here on PD data.

Scientific Reportspublished new progress about Auxilin 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Related Products of 1223001-51-1.

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

Huo, Zhixia; Chen, Lei published the artcile< Base-deactivated and alkaline-resistant chromatographic stationary phase based on functionalized polymethylsilsesquioxane microspheres>, Electric Literature of 6882-68-4, the main research area is base deactivated chromatog stationary phase functionalized polymethylsilsesquioxane microsphere; basic compounds; co-condensation; functionalization; polymethylsilsesquioxane; silanol activity.

Vinyl, chloropropyl, and mercaptopropyl functionalized particles were prepared by a two-step acidic/alk. catalyzed co-hydrolysis/condensation of methyltrimethoxysilane with a different silane precursor that carries chem. reactive functional group including vinyl, chloropropyl, and mercaptopropyl, resp. The morphol., pore structure, and functional groups of the synthesized packings were studied by SEM, nitrogen adsorption-desorption measurements, and solid-state 13C 29Si NMR spectroscopy, resp. The particles show ordered sphere, narrow particle size distribution, and mesoporous structure. The carbon contents of the microspheres are in the range of 17-19%, comparable to those of octadecyl-bonded silica packings. The three-kind of microspheres were directly used as packing materials for high-performance liquid chromatog. without size classification. The chromatog. performance of the columns was evaluated and compared with a com. available C18 phase. The results revealed that these columns possess typical reversed-phase chromatog. properties with increased hydrophobicity than polymethylsilsesquioxane and sym. peaks for basic compounds They were applied to the simultaneous separation of combination bendazol hydrochlorothiazide capsules containing polar and basic drugs with peaks identified by tandem with mass spectrometry. In general, a novel method is provided for the synthesis of different methyltrimethoxysilane-derived microspheres for high-performance liquid chromatog., which are advantageous for separating basic compounds

Journal of Separation Sciencepublished new progress about Chromatographic stationary phases (base-deactivated and alk.-resistant). 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

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