Tag: 400-500

Jmjd3 Mediates Neuropathic Pain by Inducing Macrophage Infiltration and Activation in Lumbar Spinal Stenosis Animal Model was written by Lee, Jeeyoun;Choi, Haeyoung;Park, Chansol;Jeon, Sangryong;Yune, Taeyoung. And the article was included in International Journal of Molecular Sciences in 2021.Product Details of 1373423-53-0 The following contents are mentioned in the article:

Lumbar spinal stenosis (LSS) is a major cause of chronic neuropathic back and/or leg pain. Recently, we demonstrated that a significant number of macrophages infiltrated into the cauda equina after compression injury, causing neuroinflammation, and consequently mediating neuropathic pain development and/or maintenance. However, the mol. mechanisms underlying macrophage infiltration and activation have not been elucidated. Here, we demonstrated the critical role of histone H3K27 demethylase Jmjd3 in blood-nerve barrier dysfunction following macrophage infiltration and activation in LSS rats. The LSS rat model was induced by cauda equina compression using a silicone block within the epidural spaces of the L5-L6 vertebrae with neuropathic pain developing 4 wk after compression. We found that Jmjd3 was induced in the blood vessels and infiltrated macrophages in a rat model of neuropathic pain. The blood-nerve barrier permeability in the cauda equina was increased after compression and significantly attenuated by the Jmjd3 demethylase inhibitor, GSK-J4. GSK-J4 also inhibited the expression and activation of MMP-2 and MMP-9 and significantly alleviated the loss of tight junction proteins and macrophage infiltration. Furthermore, the activation of a macrophage cell line, RAW 264.7, by LPS was significantly alleviated by GSK-J4. Finally, GSK-J4 and a potential Jmjd3 inhibitor, gallic acid, significantly inhibited mech. allodynia in LSS rats. Thus, our findings suggest that Jmjd3 mediates neuropathic pain development and maintenance by inducing macrophage infiltration and activation after cauda equina compression and thus may serve as a potential therapeutic target for LSS-induced neuropathic pain. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Product Details of 1373423-53-0).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Product Details of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Radiosensitization by histone H3 Demethylase inhibition in diffuse intrinsic pontine glioma was written by Katagi, Hiroaki;Louis, Nundia;Unruh, Dusten;Sasaki, Takahiro;He, Xingyao;Zhang, Ali;Ma, Quanhong;Piunti, Andrea;Shimazu, Yosuke;Lamano, Jonathan B.;Carcaboso, Angel M.;Tian, Xiao;Seluanov, Andrei;Gorbunova, Vera;Laurie, Kathryn L.;Kondo, Akihide;Wadhwani, Nitin R.;Lulla, Rishi;Goldman, Stewart;Venneti, Sriram;Becher, Oren J.;Zou, Lihua;Shilatifard, Ali;Hashizume, Rintaro. And the article was included in Clinical Cancer Research in 2019.Synthetic Route of C24H27N5O2 The following contents are mentioned in the article:

Purpose: Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clin. benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG. Exptl. Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quant. real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochem. of DSB markers γH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts. Results: GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of γH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy. Conclusions: Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Synthetic Route of C24H27N5O2).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. Pyrimidine derivatives have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.Synthetic Route of C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

LncRNA H19 regulates macrophage polarization and promotes Freund’s complete adjuvant-induced arthritis by upregulating KDM6A was written by Zhu, Xiaodong;Zhu, Ye;Ding, Chen;Zhang, Weiting;Guan, Huilin;Li, Chunmei;Lin, Xiao;Zhang, Yang;Huang, Chunyan;Zhang, Luyao;Yu, Xin;Zhang, Xiaomin;Zhu, Wei. And the article was included in International Immunopharmacology in 2021.Recommanded Product: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate The following contents are mentioned in the article:

Aberrant expression of long non-coding RNA (lncRNA) H19 is tightly linked to multiple steps of tumorigenesis via the modulation of cell proliferation and apoptosis; however, the pathol. significance and regulatory mechanisms of lncRNA H19 in macrophages remain obscure. To investigate whether lncRNA H19 modulates macrophage activation in rheumatoid arthritis (RA), lncRNA H19 levels in PMA-induced PBMC from patients with RA and healthy volunteers were assessed. In addition, the distribution of macrophage subsets, macrophage phenotypic characteristics, and pro-inflammatory gene expression were examined in lncRNA H19 smart silencer- or pcDNA 3.1- H19-transfected macrophages and AAV8-mediated H19 overexpression in a Freunds complete adjuvant-induced arthritis mouse model. The level of lncRNA H19 was higher in RA patients than in healthy volunteers. Silencing of lncRNA H19 altered lipopolysaccharide plus interferon-induced M1 macrophage polarization and decreased IL-6, CD80, CCL8, and CXCL10 expression in macrophages of RA patients. LncRNA H19 overexpression markedly induced IL-6, CD80, HLA-DR, KDM6A, STAT1, IRF5, CCL8, CXCL9, CXCL10, and CXCL11 expression in macrophages and promoted macrophage migration. AAV8-mediated H19 overexpression aggravated arthritis in mice by promoting M1 macrophage polarization along with iNOS, IL-6, CCL8, CXCL9, CXCL10, CXCL11, MMP3, MMP13 and COX-2 expression in mononuclear cells isolated from the swollen ankle. GSK-J4, an inhibitor of KDM6A, suppressed the activity of lncRNA H19 in macrophages and ameliorated lncRNA H19-aggravated arthritis. In summary, the current study demonstrated that lncRNA H19 is upregulated in RA patients and arthritic mice. LncRNA H19 promotes M1 macrophage polarization and aggravates arthritis by upregulating KDM6A expression. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Recommanded Product: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Recommanded Product: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Upregulation of KDM6B contributes to lipopolysaccharide-induced anxiety-like behavior via modulation of VGLL4 in mice was written by Shentu, Yangping;Tian, Qiuyun;Yang, Jinge;Liu, Xiaoyuan;Han, Yujiao;Yang, Dichen;Zhang, Nan;Fan, Xiaofang;Wang, Ping;Ma, Jianshe;Chen, Ran;Li, Dantong;Liu, Shouting;Wang, Yongyu;Mao, Sunzhong;Gong, Yongsheng;Du, Congkuo;Fan, Junming. And the article was included in Behavioural Brain Research in 2021.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate The following contents are mentioned in the article:

Histone H3K27me3 demethylase KDM6B (also known as Jumonji domain-containing protein D3, JMJD3) plays vital roles in the etiol. of inflammatory responses; however, little is known about the role of KDM6B in neuroinflammation-induced anxiety-like behavior. The present study aimed to investigate the potential role of KDM6B in lipopolysaccharide (LPS)-induced anxiety-like behavior and to evaluate whether it is associated with the modulation of vestigial-like family member 4 (VGLL4). The elevated plus maze, light-dark box, and open-field test were performed to test the anxiety-like behavior induced by LPS in C57BL/6 J male mice. Levels of relative protein expression in the hippocampus were quantified by western blotting. KDM6B inhibitor GSK-J4 and microglia inhibitor minocycline as well as adeno-associated virus of Vgll4 shRNA were used to explore the underlying mechanisms. We found that KDM6B, VGLL4, interleukin-1β (IL-1β), and ionized calcium-binding adaptor mol.-1 (Iba-1, microglia marker) protein levels were increased in LPS-dose dependent manner in the hippocampus but not in prefrontal cortex. GSK-J4 treatment attenuated LPS-induced VGLL4, the signal transducer and activator of transcription 3 (STAT3), IL-1β and Iba-1 upregulation and anxiety-like behavior. Knockdown VGLL4 with Vgll4 shRNA prevented the increase of anxiety-like behavior and levels of STAT3, IL-1β, and Iba-1 expression in the hippocampus of LPS-treated mice. Moreover, minocycline, an inhibitor of microglia treatment blunted LPS-induced anxiety-like behavior. Collectively, these results demonstrate that the induction of neuroinflammation by LPS promotes KDM6B activation in the hippocampus, and LPS-induced anxiety-like behavior is associated with upregulation of VGLL4 by KDM6B in the hippocampus. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain was written by Liu, Shuxian;Wu, Mimi;Hua, Qianqian;Lu, Daiqiang;Tian, Yuan;Yu, Helin;Cheng, Linyan;Chen, Yinqi;Cao, Jiaxin;Hu, Xin;Tan, Feng. And the article was included in Parasites & Vectors in 2020.Electric Literature of C24H27N5O2 The following contents are mentioned in the article:

Toxoplasma gondii is a zoonotic pathogen that causes toxoplasmosis and leads to serious public health problems in developing countries. However, current clin. therapeutic drugs have some disadvantages, such as serious side effects, a long course of treatment and the emergence of drug-resistant strains. The urgent need to identify novel anti-Toxoplasma drugs has initiated the effective strategy of repurposing well-characterized drugs. As a principled screening for the identification of effective compounds against Toxoplasma gondii, in the current study, a collection of 666 compounds were screened for their ability to significantly inhibit Toxoplasma growth. The inhibition of parasite growth was determined using a luminescence-based β-galactosidase activity assay. Meanwhile, the effect of compounds on the viability of host cells was measured using CCK8. To assess the inhibition of the selected compounds on discrete steps of the T. gondii lytic cycle, the invasion, intracellular proliferation and egress abilities were evaluated. Finally, a murine infection model of toxoplasmosis was used to monitor the protective efficacy of drugs against acute infection of a highly virulent RH strain. A total of 68 compounds demonstrated more than 70% parasite growth inhibition. After excluding compounds that impaired host cell viability, we further characterized two compounds, NVP-AEW541 and GSK-J4 HCl, which had IC50 values for parasite growth of 1.17μM and 2.37μM, resp. In addition, both compounds showed low toxicity to the host cell. Furthermore, we demonstrated that NVP-AEW541 inhibits tachyzoite invasion, while GSK-J4 HCl inhibits intracellular tachyzoite proliferation by halting cell cycle progression from G1 to S phase. These findings prompted us to analyze the efficacy of the two compounds in vivo by using established mouse models of acute toxoplasmosis. In addition to prolonging the survival time of mice acutely infected with T. gondii, both compounds had a remarkable ability to reduce the parasite burden of tissues. Our findings suggest that both NVP-AEW541 and GSK-J4 could be potentially repurposed as candidate drugs against T. gondii infection.[graphic not available: see fulltext]. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Electric Literature of C24H27N5O2).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Electric Literature of C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Jmjd3 is involved in the susceptibility to depression induced by maternal separation via enhancing the neuroinflammation in the prefrontal cortex and hippocampus of male rats was written by Wang, Rui;Wang, Wei;Xu, Jingjing;Liu, Dexiang;Wu, Huiran;Qin, Xiaqing;Jiang, Hong;Pan, Fang. And the article was included in Experimental Neurology in 2020.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate The following contents are mentioned in the article:

Adverse childhood experience is a major risk factor for the onset of depression in adulthood. Neuroinflammation characterized by microglial activation and cytokine secretion is involved in susceptibility to depression induced by early life stress. Jumonji domain-containing protein 3 (Jmjd3), a trimethylated lysine 27 in histone 3 (H3K27me3) demethylase, can be activated by nuclear factor-kappa B (NF-κB), further regulating the expression of pro-inflammatory cytokines and resulting in neuroinflammation. However, its involvement in susceptibility to early life stress-related depression is unknown. In the current study, maternal separation (MS) was utilized as a model of early life stress and systemic lipopolysaccharide (LPS) administration in adulthood was used as a later-life challenge. Depressive- and anxiety-like behaviors and memory impairment were detected by behavioral tests. Microglial activation, pro-inflammatory cytokine expression, and NF-κB, Jmjd3, and H3K27me3 expression were detected in the prefrontal cortex and hippocampus in both infant and adult rats. Meanwhile, the Jmjd3 inhibitor GSK-J4 was used as an intervention in vivo and in vitro. Our results showed that MS induced depression-like behaviors and synchronously caused microglial activation, pro-inflammatory cytokine over-expression, NF-κB and Jmjd3 over-expression, and decreased H3K27me3 expression in infant rats. All these alterations could also be detected in adulthood. Seven-day LPS administration in adult rats induced similar changes of behaviors and biomarkers. Interestingly, compared with rats not exposed to MS, MS-exposed rats receiving LPS administration developed more severe depression-like behaviors and neuroinflammatory status, higher levels of NF-κB and Jmjd3 expression, and lower levels of H3K27me3 expression. In addition, LPS induced microglial activation, pro-inflammatory cytokine expression and increased Jmjd3 expression in vitro. Furthermore, GSK-J4 treatment alleviated these alterations in vivo and in vitro. Thus, our data indicate that Jmjd3 is involved in the susceptibility to depression induced by MS via enhancement of neuroinflammation in the prefrontal cortex and hippocampus of rats. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Targeting P16INK4A in uterine serous carcinoma through inhibition of histone demethylation was written by Xiao, Zhen;He, Yingying;Liu, Chongya;Xiang, Lin;Yi, Jingyan;Wang, Min;Shen, Tingting;Shen, Lanlin;Xue, Yijue;Shi, Hong;Liu, Pixu. And the article was included in Oncology Reports in 2019.Application In Synthesis of Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate The following contents are mentioned in the article:

Uterine serous carcinoma (USC) is a subtype of endometrial cancer. Compared with endometrial endometroid carcinoma, the majority of USC cases are more aggressive. Cyclin-dependent kinase inhibitor 2A (P16INK4A) is a canonical tumor suppressor that blocks cell cycle progression; however, P16INK4A is overexpressed in USC. The aim of the present study was to determine the role of P16INK4A in P16INK4A-pos. endometrial cancer, with the hope of elucidating a novel therapeutic approach for this type of malignancy. A total of 2 endometrial cancer cell lines, ETN-1 and EFE-184, were selected for further investigation, due to them being known to express high levels of P16INK4A. Using short hairpin RNA targeting P16INK4A, P16INK4A was downregulated in these cancer cell lines. Cell viability and migration were examined via 2D/3D clonogenic and wound healing assays. Subsequently, GSK-J4, a histone demethylase inhibitor, was employed to deplete P16INK4A in these cancer cell lines and an ex vivo culture system of a patient-derived xenograft (PDX) endometrial tumor sample. Following P16INK4A knockdown, the proliferation and migration of ETN-1 and EFE-184 cells markedly declined. When exposed to GSK-J4, the levels of KDM6B and P16INK4A were almost completely abrogated, and the cell viability was significantly reduced in these cell lines and the ex vivo-cultured PDX tumor explants. The association between the levels of P16INK4A, lysine demethylase 6B (KDM6B) and the methylation status of histone 3 lysine 27 (H3K27) in these cell lines and the human USC tumor sample was also demonstrated. P16INK4A appears to be oncogenic in a number of endometrial cancer cell lines. The level of P16INK4A is associated with the methylation status of H3K27. Increased methylation of H3K27 coexists with downregulation of KDM6B and, subsequently, P16INK4A, which reduces cell proliferation and invasiveness in endometrial cancer. The observations of the present study may enable the development of a novel therapeutic strategy for P16INK4A-pos. endometrial cancer, particularly USC. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Application In Synthesis of Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Application In Synthesis of Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

GSK-J4 induces cell cycle arrest and apoptosis via ER stress and the synergism between GSK-J4 and decitabine in acute myeloid leukemia KG-1a cells was written by Chu, Xuan;Zhong, Liang;Yu, Lihua;Xiong, Ling;Li, Jian;Dan, Wenran;Ye, Jiao;Liu, Chen;Luo, Xu;Liu, Beizhong. And the article was included in Cancer Cell International in 2020.Computed Properties of C24H27N5O2 The following contents are mentioned in the article:

GSK-J4 is the inhibitor of H3K27me3 demethylase. Recent studies demonstrated that GSK-J4 could affect the proliferation and apoptosis of a variety of cancer cells. However, the effects and underlying mechanisms of GSK-J4 on the proliferation and apoptosis of human acute myeloid leukemia (AML) KG-1a cells have not been explored thoroughly. The effect of GSK-J4 on cell proliferation was assessed with CCK8, while cell cycle distribution and apoptosis were analyzed using flow cytometry. The proteins related to cell cycle, cell apoptosis, endoplastic reticulum (ER) stress and PKC-α/p-Bcl2 pathway were detected by Western blotting. The expression level of PKC-α mRNA was measured by quant. real-time PCR. ER stress inhibitor 4-Ph butyric acid (4-PBA) was used to explore the role of ER stress in GSK-J4 induced cell-cycle arrest and cell apoptosis. The combination effects of Decitabine and GSK-J4 on KG-1a cells proliferation and apoptosis were also evaluated by CCK8, flow cytometry and immunoblot anal. Results: GSK-J4 reduced cell viability and arrested cell cycle progression at the S phase by decreasing the expression of CyclinD1 and CyclinA2 and increasing that of P21. Moreover, GSK-J4 enhanced the expression of apoptosis-related proteins (cle-caspase-9 and bax) and inhibited PKC-a/p-Bcl2 pathway to promote cell apoptosis. In addition, ER stress-related proteins (caspase-12, GRP78 and ATF4) were increased markedly after exposure to GSK-J4. The effects of GSK-J4 on cell cycle, apoptosis and PKC-a/p-Bcl2 pathway were attenuated after treatment with ER stress inhibitor. Furthermore, decitabine could significantly inhibit the proliferation and induce the apoptosis of KG-1a cells after combined treatment with GSK-J4. Taken together, this study provided evidence that ER stress could regulate the process of GSK-J4-induced cell cycle arrest, cell apoptosis and PKC-α/p-bcl2 pathway inhibition and demonstrated a potential combinatory effect of decitabine and GSK-J4 on leukemic cell proliferation and apoptosis. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Computed Properties of C24H27N5O2).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Computed Properties of C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of H3K27me3 demethylases attenuates asthma by reversing the shift in airway smooth muscle phenotype was written by Yu, Qijun;Yu, Xiaowei;Zhao, Wenxue;Zhu, Manni;Wang, Zhengxia;Zhang, Jiaxiang;Huang, Mao;Zeng, Xiaoning. And the article was included in Clinical & Experimental Allergy in 2018.Product Details of 1373423-53-0 The following contents are mentioned in the article:

The shift in airway smooth muscle cells (ASMCs) phenotype between proliferation and contraction during asthma has been reported recently, highlighting a role of ASMCs plasticity in the pathophysiol. of asthma. As an event involved in epigenetic post-translational modification, histone H3 lysine27 (H3K27) demethylation has attracted significant attention with respect to the epigenetic changes in diverse cells; however, little is known about its contribution to the switching of ASMCs phenotype in asthma. To investigate the role of trimethylated H3K27 (H3k27me3) demethylation in ASM remodeling as well as the underling mechanism. Mice were exposed five times a week to house dust mite (HDM) extract for 5 wk. Lung function was measured following the final HDM challenge. Airway inflammation and remodeling were then assessed in lungs of individual mice. Human ASMCs were purchased from Sciencell Research Laboratories Proliferation, synthesis, migration and contraction of ASMCs were analyzed, resp. We observed demethylation at H3k27me3 sites in lungs harvested from mice exposed to HDM extract Administration of a selective inhibitor of H3K27 demethylase (GSK-J4) could ameliorate the classical hallmarks of asthma, such as airway hyperresponsiveness, airway inflammation and remodeling. We established a proliferative as well as a contractive model of human ASMCs to explore the impacts of H3K27 demethylase inhibition on ASMCs phenotype. Our results indicated that GSK-J4 decreased ASMCs proliferation and migration elicited by PDGF through the Akt/JNK signalling; GSK-J4 also prevented the upregulation of contractile proteins in ASMCs induced by TGF-β through the Smad3 pathway. Inhibition of H3K27me3 demethylation alleviated the development of asthmatic airway disease in vivo and modulated ASMCs phenotype in vitro. Collectively, our findings highlight a role of H3K27me3 demethylation in exptl. asthma and ASMCs phenotype switch. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Product Details of 1373423-53-0).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Product Details of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays was written by Lobo-Silva, Jessica;Cabral, Fernanda J.;Amaral, Murilo S.;Miyasato, Patricia A.;de Freitas, Rafaela Paula;Pereira, Adriana S. A.;Khouri, Mariana I.;Barbosa, Mayra M. F.;Ramos, Pablo I. P.;Leite, Luciana C. C.;Asojo, Oluwatoyin A.;Nakano, Eliana;Verjovski-Almeida, Sergio;Farias, Leonardo P.. And the article was included in Parasites & Vectors in 2020.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate The following contents are mentioned in the article:

Abstract: Background: Schistosomiasis chemotherapy is largely based on praziquantel (PZQ). Although PZQ is very safe and tolerable, it does not prevent reinfection and emerging resistance is a primary concern. Recent studies have shown that the targeting of epigenetic machinery in Schistosoma mansoni may result in severe alterations in parasite development, leading to death. This new route for drug discovery in schistosomiasis has focused on classes of histone deacetylases (HDACs) and histone acetyltransferases (HATs) as epigenetic drug targets. Schistosoma histone demethylases also seem to be important in the transition of cercariae into schistosomula, as well as sexual differentiation in adult worms. Methods: The Target-Pathogen database and mol. docking assays were used to prioritize the druggability of S. mansoni histone demethylases. The transcription profile of Smp_03400 was re-analyzed using available databases. The effect of GSK-J4 inhibitor in schistosomula and adult worms’ motility/viability/oviposition was assessed by in vitro assays. Ultrastructural anal. was performed on adult worms exposed to GSK-J4 by SEM, while internal structures and muscle fiber integrity was investigated by confocal microscopy after Langeron’s carmine or phalloidin staining. Results: The present evaluation of the potential druggability of 14 annotated S. mansoni demethylase enzymes identified the S. mansoni ortholog of human KDM6A/UTX (Smp_034000) as the most suitable druggable target. In silico anal. and mol. modeling indicated the potential for cofactor displacement by the chem. probe GSK-J4. Our re-anal. of transcriptomic data revealed that Smp_034000 expression peaks at 24 h in newly transformed schistosomula and 5-wk-old adult worms. Moreover, this gene was highly expressed in the testes of mature male worms compared to the rest of the parasite body. In in vitro schistosome cultures, treatment with GSK-J4 produced striking effects on schistosomula mortality and adult worm motility and mortality, as well as egg oviposition, in a dose- and time-dependent manner. Unexpectedly, western blot assays did not demonstrate overall modulation of H3K27me3 levels in response to GSK-J4. Confocal and SEM revealed the loss of original features in muscle fibers and alterations in cell-cell contact following GSK-J4 treatment. Conclusions: GSK-J4 presents promising potential for antischistosomal control; however, the underlying mechanisms warrant further investigation.[graphic not available: see fulltext]. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia