Category: pyrimidines

Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response was written by Amin, Ruhul;Shukla, Anjali;Zhu, Jacqueline Jufen;Kim, Sohyoung;Wang, Ping;Tian, Simon Zhongyuan;Tran, Andy D.;Paul, Debasish;Cappell, Steven D.;Burkett, Sandra;Liu, Huaitian;Lee, Maxwell P.;Kruhlak, Michael J.;Dwyer, Jennifer E.;Simpson, R. Mark;Hager, Gordon L.;Ruan, Yijun;Hunter, Kent W.. And the article was included in Nature Communications in 2021.Application of 1373423-53-0 The following contents are mentioned in the article:

Mech. signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor pos. (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis. 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 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 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. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Application of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of H3K4 demethylation induces autophagy in cancer cell lines was written by Wang, Zhen;Long, Qiao-Yun;Chen, Lin;Fan, Jia-Dong;Wang, Zhao-Ning;Li, Lian-Yun;Wu, Min;Chen, Xuefeng. And the article was included in Biochimica et Biophysica Acta, Molecular Cell Research in 2017.COA of Formula: C24H27N5O2 The following contents are mentioned in the article:

Epigenetic factors and related small mols. have emerged to be strongly involved in autophagy process. Here we report that 2-PCPA and GSK-LSD1, two inhibitors of histone H3K4 demethylase KDM1A/LSD1, induce autophagy in multiple mammalian cell lines. The two small mols. induce accumulation of LC3II, formation of autophagosome and autolysosome, and SQSTM1/p62 degradation 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but does not inducing cell death. Exogenous expression of KDM1A/LSD1 impaired the autophagic phenotypes triggered by 2-PCPA. The autophagy induced by 2-PCPA requires LC3-II processing machinery. But depletion of BECN1 and ULK1 with siRNA did not affect the LC3-II accumulation triggered by 2-PCPA. 2-PCPA treatment induces the change of global gene expression program, including a series of autophagy-related genes, such as SQSTM1/p62. Taken together, our data indicate that KDM1A/LSD1 inhibitors induce autophagy through affecting the expression of autophagy-related genes and in a BECN1-independent manner. 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: 1373423-53-0COA of Formula: 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. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.COA of Formula: C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fibroblast growth factor receptor inhibitors was written by Suneel Kumar, B. V. S.;Narasu, Lakshmi;Gundla, Rambabu;Dayam, Raveendra;Sarma, J. A. R. P.. And the article was included in Current Pharmaceutical Design in 2013.Electric Literature of C28H41N7O3 The following contents are mentioned in the article:

A review. Fibroblast growth factor receptors (FGFRs) play an important role in embryonic development, angiogenesis, wound healing, cell proliferation and differentiation. The fibroblast growth factor receptor (FGFR) isoforms have been under intense scrutiny for effective anticancer drug candidates. The fibroblast growth factor (FGF) and its receptor (FGFR) provide another pathway that seems critical to monitoring angiogenesis. Recent findings suggest that FGFR mediates signaling, regulates the PKM2 activity, and plays a crucial role in cancer metabolism The current review also covers the recent findings on the role of FGFR1 in cancer metabolism This paper reviews the progress, mechanism, and binding modes of recently known kinase inhibitors such as PD173074, SU series and other inhibitors still under clin. development. Some of the structural classes that will be highlighted in this review include Pyrido[2,3-d]pyrimidines, Indolin-2-one, Pyrrolo[2,1-f][1,2,4]triazine, Pyrido[2,3-d]pyrimidin-7(8H)-one, and 1,6-Naphthyridin-2(1H)-ones. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Electric Literature of C28H41N7O3).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. 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.Electric Literature of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Epigenetic Regulation of Wnt Signaling by Carboxamide-Substituted Benzhydryl Amines that Function as Histone Demethylase Inhibitors was written by Zhang, Wen;Sviripa, Vitaliy M.;Xie, Yanqi;Yu, Tianxin;Haney, Meghan G.;Blackburn, Jessica S.;Adeniran, Charles A.;Zhan, Chang-Guo;Watt, David S.;Liu, Chunming. And the article was included in iScience in 2020.HPLC of Formula: 1373422-53-7 The following contents are mentioned in the article:

Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (å°?catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3鈥瞫 lysine 9 (H3K9Me2), a repressive marker for transcription. Inhibiting KDM3 increased H3K9Me2 levels, repressed Wnt target genes, and curtailed in vitro CRC cell proliferation. CBA-1 also exhibited in vivo inhibition of Wnt signaling in a zebrafish model without displaying in vivo toxicity. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7HPLC of Formula: 1373422-53-7).

3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. 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.HPLC of Formula: 1373422-53-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Integrated Drug Expression Analysis for leukemia: an integrated in silico and in vivo approach to drug discovery was written by Ung, M. H.;Sun, C.-H.;Weng, C.-W.;Huang, C.-C.;Lin, C.-C.;Liu, C.-C.;Cheng, C.. And the article was included in Pharmacogenomics Journal in 2017.COA of Formula: C28H41N7O3 The following contents are mentioned in the article:

Screening for drug compounds that exhibit therapeutic properties in the treatment of various diseases remains a challenge even after considerable advancements in biomedical research. Here, we introduce an integrated platform that exploits gene expression compendia generated from drug-treated cell lines and primary tumor tissue to identify therapeutic candidates that can be used in the treatment of acute myeloid leukemia (AML). Our framework combines these data with patient survival information to identify potential candidates that presumably have a significant impact on AML patient survival. We use a drug regulatory score (DRS) to measure the similarity between drug-induced cell line and patient tumor gene expression profiles, and show that these computed scores are highly correlated with in vitro metrics of pharmacol. activity. Furthermore, we conducted several in vivo validation experiments of our potential candidate drugs in AML mouse models to demonstrate the accuracy of our in silico predictions. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7COA of Formula: C28H41N7O3).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.COA of Formula: C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade was written by Romero, Octavio A.;Vilarrubi, Andrea;Alburquerque-Bejar, Juan J.;Gomez, Antonio;Andrades, Alvaro;Trastulli, Deborah;Pros, Eva;Setien, Fernando;Verdura, Sara;Farre, Lourdes;Martin-Tejera, Juan F.;Llabata, Paula;Oaknin, Ana;Saigi, Maria;Piulats, Josep M.;Matias-Guiu, Xavier;Medina, Pedro P.;Vidal, August;Villanueva, Alberto;Sanchez-Cespedes, Montse. And the article was included in Nature Communications in 2021.SDS of cas: 1373423-53-0 The following contents are mentioned in the article:

Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumors. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), had strong anti-tumor effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients. 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: 1373423-53-0SDS of cas: 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. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.SDS of cas: 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Drug-Induced Death Signaling Strategy Rapidly Predicts Cancer Response to Chemotherapy was written by Montero, Joan;Sarosiek, Kristopher A.;De Angelo, Joseph D.;Maertens, Ophelia;Ryan, Jeremy;Ercan, Dalia;Piao, Huiying;Horowitz, Neil S.;Berkowitz, Ross S.;Matulonis, Ursula;Janne, Pasi A.;Amrein, Philip C.;Cichowski, Karen;Drapkin, Ronny;Letai, Anthony. And the article was included in Cell (Cambridge, MA, United States) in 2015.Computed Properties of C28H41N7O3 The following contents are mentioned in the article:

There is a lack of effective predictive biomarkers to precisely assign optimal therapy to cancer patients. While most efforts are directed at inferring drug response phenotype based on genotype, there is very focused and useful phenotypic information to be gained from directly perturbing the patient’s living cancer cell with the drug(s) in question. To satisfy this unmet need, we developed the Dynamic BH3 Profiling technique to measure early changes in net pro-apoptotic signaling at the mitochondrion (“priming”) induced by chemotherapeutic agents in cancer cells, not requiring prolonged ex vivo culture. We find in cell line and clin. experiments that early drug-induced death signaling measured by Dynamic BH3 Profiling predicts chemotherapy response across many cancer types and many agents, including combinations of chemotherapies. We propose that Dynamic BH3 Profiling can be used as a broadly applicable predictive biomarker to predict cytotoxic response of cancers to chemotherapeutics in vivo. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Computed Properties of C28H41N7O3).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. 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.Computed Properties of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

KDM6B-dependent chromatin remodeling underpins effective virus-specific CD8+ T cell differentiation was written by Li, Jasmine;Hardy, Kristine;Olshansky, Moshe;Barugahare, Adele;Gearing, Linden J.;Prier, Julia E.;Sng, Xavier Y. X.;Nguyen, Michelle Ly Thai;Piovesan, Dana;Russ, Brendan E.;La Gruta, Nicole L.;Hertzog, Paul J.;Rao, Sudha;Turner, Stephen J.. And the article was included in Cell Reports in 2021.Reference of 1373423-53-0 The following contents are mentioned in the article:

Naive CD8⁺ T cell activation results in an autonomous program of cellular proliferation and differentiation. However, the mechanisms that underpin this process are unclear. Here, we profile genome-wide changes in chromatin accessibility, gene transcription, and the deposition of a key chromatin modification (H3K27me3) early after naive CD8⁺ T cell activation. Rapid upregulation of the histone demethylase KDM6B prior to the first cell division is required for initiating H3K27me3 removal at genes essential for subsequent T cell differentiation and proliferation. Inhibition of KDM6B-dependent H3K27me3 demethylation limits the magnitude of an effective primary virus-specific CD8⁺ T cell response and the formation of memory CD8⁺ T cell populations. Accordingly, we define the early spatiotemporal events underpinning early lineage-specific chromatin reprogramming that are necessary for autonomous CD8⁺ T cell proliferation and differentiation. 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: 1373423-53-0Reference 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. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. 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.Reference of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rotational Freedom, Steric Hindrance, and Protein Dynamics Explain BLU554 Selectivity for the Hinge Cysteine of FGFR4 was written by Lin, Xiaojing;Yosaatmadja, Yuliana;Kalyukina, Maria;Middleditch, Martin J.;Zhang, Zhen;Lu, Xiaoyun;Ding, Ke;Patterson, Adam V.;Smaill, Jeff B.;Squire, Christopher J.. And the article was included in ACS Medicinal Chemistry Letters in 2019.Product Details of 219580-11-7 The following contents are mentioned in the article:

Aberration in FGFR4 signaling drives carcinogenesis and progression in a subset of hepatocellular carcinoma (HCC) patients, thereby making FGFR4 an attractive mol. target for this disease. Selective FGFR4 inhibition can be achieved through covalently targeting a poorly conserved cysteine residue in the FGFR4 kinase domain. We report mass spectrometry assays and cocrystal structures of FGFR4 in covalent complex with the clin. candidate BLU554 and with a series of four structurally related inhibitors that define the inherent reactivity and selectivity profile of these mols. We further reveal the structure of FGFR1 with one of our inhibitors and show that off-target covalent binding can occur through an alternative conformation that supports targeting of a cysteine conserved in all members of the FGFR family. Collectively, we propose that rotational freedom, steric hindrance, and protein dynamics explain the exceptional selectivity profile of BLU554 for targeting FGFR4. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Product Details of 219580-11-7).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Product Details of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1 was written by Piechowicz, Katarzyna A.;Truong, Eric C.;Javed, Kashif M.;Chaney, Rachelle R.;Wu, Johnny Y.;Phuan, Puay W.;Verkman, Alan S.;Anderson, Marc O.. And the article was included in Journal of Enzyme Inhibition and Medicinal Chemistry in 2016.COA of Formula: C7H10N2OS The following contents are mentioned in the article:

Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca²⁺ activated Cl^– channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and elec. excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. The authors found that very little structural variation of was tolerated, with most compounds showing no activity at 10 渭M. The most potent compound in the series, which substitutes 4-methoxyphenyl in with 2-thiophene, had IC₅₀ 鈭? 渭M for inhibition of TMEM16A chloride conductance. This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3COA of Formula: C7H10N2OS).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.COA of Formula: C7H10N2OS

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia