Day: November 28, 2022

Pancreatic cancer organoids recapitulate disease and allow personalized drug screening was written by Driehuis, Else;van Hoeck, Arne;Moore, Kat;Kolders, Sigrid;Francies, Hayley E.;Gulersonmez, M. Can;Stigter, Edwin C. A.;Burgering, Boudewijn;Geurts, Veerle;Gracanin, Ana;Bounova, Gergana;Morsink, Folkert H.;Vries, Robert;Boj, Sylvia;van Es, Johan;Offerhaus, G. Johan A.;Kranenburg, Onno;Garnett, Mathew J.;Wessels, Lodewyk;Cuppen, Edwin;Brosens, Lodewijk A. A.;Clevers, Hans. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2019.SDS of cas: 219580-11-7 The following contents are mentioned in the article:

We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histol. and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-neg. tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-pos. tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs. 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: 219580-11-7SDS of cas: 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. 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. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.SDS of cas: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mesenchymal-Mode Migration Assay and Antimetastatic Drug Screening with High-Throughput Microfluidic Channel Networks was written by Zhang, Yuanqing;Zhang, Weijia;Qin, Lidong. And the article was included in Angewandte Chemie, International Edition in 2014.Synthetic Route of C28H41N7O3 The following contents are mentioned in the article:

Increasing evidence shows that activated mesenchymal migration is a key process of the metastatic cascade. Cancer cells usually gain such migratory capability through an epithelial-to-mesenchymal transition. Herein we present a high-throughput microfluidic device with 3120 microchambers to specifically monitor mesenchymal migration. Through imaging of the whole chip and statistical anal., we can evaluate the two key factors of velocity and percentage related to cell migratory capacity at different cell densities in culture. We also used the device to screen antimetastatic drugs for their inhibition of mesenchymal migration and prevention of metastatic malignancy. This device will provide an excellent platform for biologists to gain a better understanding of cancer metastasis. 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: 219580-11-7Synthetic Route 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. 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 also play an important role in drug development, either in concert with other compounds or on their own.Synthetic Route of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

NMR backbone assignments of the tyrosine kinase domain of human fibroblast growth factor receptor 3 in apo state and in complex with inhibitor PD173074 was written by Sanfelice, Domenico;Koss, Hans;Bunney, Tom D.;Thompson, Gary S.;Farrell, Brendan;Katan, Matilda;Breeze, Alexander L.. And the article was included in Biomolecular NMR Assignments in 2018.Name: 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea The following contents are mentioned in the article:

Fibroblast growth factors receptors (FGFR) are transmembrane protein tyrosine kinases involved in many cellular process, including growth, differentiation and angiogenesis. Dysregulation of FGFR enzymic activity is associated with developmental disorders and cancers; therefore FGFRs have become attractive targets for drug discovery, with a number of agents in late-stage clin. trials. Here, we present the backbone resonance assignments of FGFR3 tyrosine kinase domain in the ligand-free form and in complex with the canonical FGFR kinase inhibitor PD173074. Anal. of chem. shift changes upon inhibitor binding highlights a characteristic pattern of allosteric network perturbations that is of relevance for future drug discovery activities aimed at development of conformationally-selective FGFR inhibitors. 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: 219580-11-7Name: 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea).

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. 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.Name: 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Human UTY(KDM6C) is a male-specific Nε-methyl lysyl demethylase was written by Walport, Louise J.;Hopkinson, Richard J.;Vollmar, Melanie;Madden, Sarah K.;Gileadi, Carina;Oppermann, Udo;Schofield, Christopher J.;Johansson, Catrine. And the article was included in Journal of Biological Chemistry in 2014.COA of Formula: C22H23N5O2 The following contents are mentioned in the article:

The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of Nε-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochem. studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallog. analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors. 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: 1373422-53-7COA of Formula: C22H23N5O2).

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. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.COA of Formula: C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors was written by Reigan, Philip;Gbaj, Abdul;Stratford, Ian J.;Bryce, Richard A.;Freeman, Sally. And the article was included in European Journal of Medicinal Chemistry in 2008.Name: 5-Chloro-7H-pyrrolo[2,3-d]pyrimidine The following contents are mentioned in the article:

Thymidine phosphorylase (TP) is over-expressed in various tumor types and plays an important role in tumor angiogenesis, growth, invasion and metastasis. The enzymic activity of TP is required for the angiogenic effect of TP, therefore, inhibitors of TP are of significant interest in cancer chemotherapy. A series of xanthine oxidase (XO) activated prodrugs of known inhibitors of TP have been designed and synthesized with the ultimate intent of improving tumor selectivity and pharmacokinetic characteristics. These prodrugs were not inhibitors of TP, but were selectively oxidized by XO at C-2 and/or C-4 of the uracil ring moiety to generate the desired TP inhibitor. Mol. modeling of both the TP inhibitors and XO-activated prodrugs rationalized their binding in the active site of the human TP crystal structure. This study involved multiple reactions and reactants, such as 5-Chloro-7H-pyrrolo[2,3-d]pyrimidine (cas: 1041864-02-1Name: 5-Chloro-7H-pyrrolo[2,3-d]pyrimidine).

5-Chloro-7H-pyrrolo[2,3-d]pyrimidine (cas: 1041864-02-1) 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.Name: 5-Chloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1 was written by Yoza, Kaito;Himeno, Rika;Amano, Shinjiro;Kobashigawa, Yoshihiro;Amemiya, Shun;Fukuda, Natsuki;Kumeta, Hiroyuki;Morioka, Hiroshi;Inagaki, Fuyuhiko. And the article was included in Genes to Cells in 2016.Category: pyrimidines The following contents are mentioned in the article:

Over-expression and aberrant activation of tyrosine kinases occur frequently in human cancers. Various tyrosine kinase inhibitors (TKIs) are under clin. use, but acquisition of resistance to these drugs is a major problem. Here, we studied the interaction between two drug-resistant mutants of fibroblast growth factor receptor 1 (FGFR1), N546K and V561M, and four ATP-competitive inhibitors, ponatinib, dovitinib, PD173074 and BGJ-398. Among these protein-drug systems, the only marked reduction in affinity was that of PD173074 for the V561M mutant. We also examined the interaction of these FGFR1 variants to AMP-PNP, a nonhydrolyzable analog of ATP, and showed that N546K showed increased affinity for the ATP analog as compared with the wild type. These findings will help to clarify the mechanism of drug resistance in mutant tyrosine kinases. 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: 219580-11-7Category: pyrimidines).

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. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis was written by Leng, Xue-Yuan;Yang, Jia;Fan, Heng;Chen, Qian-Yun;Cheng, Bing-Jie;He, Hong-Xia;Gao, Fei;Zhu, Feng;Yu, Ting;Liu, Yu-Jin. And the article was included in International Immunopharmacology in 2022.Electric Literature of C22H23N5O2 The following contents are mentioned in the article:

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiol. and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of mol. biol. and immunol. techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theor. basis for understanding the pathogenesis and potential therapeutic targets of UC. 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: 1373422-53-7Electric Literature of C22H23N5O2).

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. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. 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.Electric Literature of C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A Structure-Guided Approach to Creating Covalent FGFR Inhibitors was written by Zhou, Wenjun;Hur, Wooyoung;McDermott, Ultan;Dutt, Amit;Xian, Wa;Ficarro, Scott B.;Zhang, Jianming;Sharma, Sreenath V.;Brugge, Joan;Meyerson, Matthew;Settleman, Jeffrey;Gray, Nathanael S.. And the article was included in Chemistry & Biology (Cambridge, MA, United States) in 2010.Category: pyrimidines The following contents are mentioned in the article:

Summary: The fibroblast growth factor receptor tyrosine kinases (FGFR1, 2, 3, and 4) represent promising therapeutic targets in a number of cancers. We have developed the first potent and selective irreversible inhibitor of FGFR1, 2, 3, and 4, which we named FIIN-1 that forms a covalent bond with cysteine 486 located in the P loop of the FGFR1 ATP binding site. We demonstrated that the inhibitor potently inhibits Tel-FGFR1-transformed Ba/F3 cells (EC₅₀ = 14 nM) as well as numerous FGFR-dependent cancer cell lines. A biotin-derivatized version of the inhibitor, FIIN-1-biotin, was shown to covalently label FGFR1 at Cys486. FIIN-1 is a useful probe of FGFR-dependent cellular phenomena and may provide a starting point of the development of therapeutically relevant irreversible inhibitors of wild-type and drug-resistant forms of FGFR kinases. 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: 219580-11-7Category: pyrimidines).

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. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Osmometric studies on self-association of pyrimidines in aqueous solutions: evidence for involvement of hydrophobic interactions was written by Plesiewicz, Ewa;Stepien, Elzbieta;Bolewska, Krystyna;Wierzchowski, K. L.. And the article was included in Biophysical Chemistry in 1976.HPLC of Formula: 39513-47-8 The following contents are mentioned in the article:

Vapor pressure osmometric studies were performed on stacking self-association of 25 uracil derivatives variously C- and N-substituted with polar and alkyl groups in aqueous solution at various temperatures The respective equilibrium association constants KSt were computed on the assumption of the isodesmic model of self-association Enthalpies of association for most of the compounds studied were obtained from the temperature-dependence of KSt, according to the van’t Hoff equation. Anal. of the equilibrium and thermodn. parameters in terms of the association mechanism demonstrated the involvement of classical hydrophobic interactions in the stabilization of complexes of di- and higher alkylated uracils. Data for the derivatives substituted with polar groups proved consistent with the predominant involvement of dipole-induced dipole forces in the association This study involved multiple reactions and reactants, such as Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8HPLC of Formula: 39513-47-8).

Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.HPLC of Formula: 39513-47-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors was written by Bavetsias, Vassilios;Lanigan, Rachel M.;Ruda, Gian Filippo;Atrash, Butrus;McLaughlin, Mark G.;Tumber, Anthony;Mok, N. Yi;Le Bihan, Yann-Vai;Dempster, Sally;Boxall, Katherine J.;Jeganathan, Fiona;Hatch, Stephanie B.;Savitsky, Pavel;Velupillai, Srikannathasan;Krojer, Tobias;England, Katherine S.;Sejberg, Jimmy;Thai, Ching;Donovan, Adam;Pal, Akos;Scozzafava, Giuseppe;Bennett, James M.;Kawamura, Akane;Johansson, Catrine;Szykowska, Aleksandra;Gileadi, Carina;Burgess-Brown, Nicola A.;von Delft, Frank;Oppermann, Udo;Walters, Zoe;Shipley, Janet;Raynaud, Florence I.;Westaway, Susan M.;Prinjha, Rab K.;Fedorov, Oleg;Burke, Rosemary;Schofield, Christopher J.;Westwood, Isaac M.;Bountra, Chas;Muller, Susanne;van Montfort, Rob L. M.;Brennan, Paul E.;Blagg, Julian. And the article was included in Journal of Medicinal Chemistry in 2016.Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid The following contents are mentioned in the article:

We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-Me lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity vs. the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me₃ and H3K4Me₃ demethylation in a cell-based assay. 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: 1373422-53-7Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid).

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. 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. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia