Category: pyrimidines

Histone deacetylase inhibitors antagonize distinct pathways to suppress tumorigenesis of embryonal rhabdomyosarcoma was written by Vleeshouwer-Neumann, Terra;Phelps, Michael;Bammler, Theo K.;MacDonald, James W.;Jenkins, Isaac;Chen, Eleanor Y.. And the article was included in PLoS One in 2015.SDS of cas: 219580-11-7 The following contents are mentioned in the article:

Embryonal rhabdomyosarcoma (ERMS) is the most common soft tissue cancer in children. The prognosis of patients with relapsed or metastatic disease remains poor. ERMS genomes show few recurrent mutations, suggesting that other mol. mechanisms such as epigenetic regulation might play a major role in driving ERMS tumor biol. In this study, we have demonstrated the diverse roles of histone deacetylases (HDACs) in the pathogenesis of ERMS by characterizing effects of HDAC inhibitors, trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; also known as vorinostat) in vitro and in vivo. TSA and SAHA suppress ERMS tumor growth and progression by inducing myogenic differentiation as well as reducing the self-renewal and migratory capacity of ERMS cells. Differential expression profiling and pathway anal. revealed downregulation of key oncogenic pathways upon HDAC inhibitor treatment. By gain-of-function, loss-of-function, and chromatin immunoprecipitation (ChIP) studies, we show that Notch1- and EphrinB1- mediated pathways are regulated by HDACs to inhibit differentiation and enhance migratory capacity of ERMS cells, resp. Our study demonstrates that aberrant HDAC activity plays a major role in ERMS pathogenesis. Druggable targets in the mol. pathways affected by HDAC inhibitors represent novel therapeutic options for ERMS patients. 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. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. 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

A KDM6 inhibitor potently induces ATF4 and its target gene expression through HRI activation and by UTX inhibition was written by Kitajima, Shojiro;Sun, Wendi;Lee, Kian Leong;Ho, Jolene Caifeng;Oyadomari, Seiichi;Okamoto, Takashi;Masai, Hisao;Poellinger, Lorenz;Kato, Hiroyuki. And the article was included in Scientific Reports 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:

UTX/KDM6A encodes a major histone H3 lysine 27 (H3K27) demethylase, and is frequently mutated in various types of human cancers. Although UTX appears to play a crucial role in oncogenesis, the mechanisms involved are still largely unknown. Here we show that a specific pharmacol. inhibitor of H3K27 demethylases, GSK-J4, induces the expression of transcription activating factor 4 (ATF4) protein as well as the ATF4 target genes (e.g. PCK2, CHOP, REDD1, CHAC1 and TRIB3). ATF4 induction by GSK-J4 was due to neither transcriptional nor post-translational regulation. In support of this view, the ATF4 induction was almost exclusively dependent on the heme-regulated eIF2伪 kinase (HRI) in mouse embryonic fibroblasts (MEFs). Gene expression profiles with UTX disruption by CRISPR-Cas9 editing and the following stable re-expression of UTX showed that UTX specifically suppresses the expression of the ATF4 target genes, suggesting that UTX inhibition is at least partially responsible for the ATF4 induction. Apoptosis induction by GSK-J4 was partially and cell-type specifically correlated with the activation of ATF4-CHOP. These findings highlight that the anti-cancer drug candidate GSK-J4 strongly induces ATF4 and its target genes via HRI activation and raise a possibility that UTX might modulate cancer formation by regulating the HRI-ATF4 axis. 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. 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. 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.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

Histone demethylase KDM6B regulates human podocyte differentiation in vitro was written by Guo, Yanyan;Xiong, Zuying;Guo, Xiaoqiang. And the article was included in Biochemical Journal in 2019.Electric Literature of C24H27N5O2 The following contents are mentioned in the article:

Podocytes are terminally differentiated and highly specialized glomerular cells, which have an essential role as a filtration barrier against proteinuria. Histone methylation has been shown to influence cell development, but its role in podocyte differentiation is less understood. In this study, we first examined the expression pattern of histone demethylase KDM6B at different times of cultured human podocytes in vitro. We found that the expression of KDM6B and podocyte differentiation markers WT1 and Nephrin are increased in the podocyte differentiation process. In cultured podocytes, KDM6B knockdown with siRNA impaired podocyte differentiation and led to expression down-regulation of WT1 and Nephrin. The treatment of podocytes with GSK-J4, a specific KDM6B inhibitor, can also obtain similar results. Overexpression of WT1 can rescue differentiated phenotype impaired by disruption of KDM6B. ChIP (chromatin immunoprecipitation) assay further indicated that KDM6B can bind the promoter region of WT1 and reduce the histone H3K27 methylation. Podocytes in glomeruli from nephrotic patients exhibited increased KDM6B contents and reduced H3K27me3 levels. These data suggest a role for KDM6B as a regulator of podocyte differentiation, which is important for the understanding of podocyte function in kidney development and related diseases. 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. 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 C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors was written by Hu, Jianping;Wang, Xin;Chen, Lin;Huang, Min;Tang, Wei;Zuo, Jianping;Liu, Yu-Chih;Shi, Zhe;Liu, Rongfeng;Shen, Jingkang;Xiong, Bing. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2016.Product Details of 1373422-53-7 The following contents are mentioned in the article:

The histone methylation on lysine residues is one of the most studied posttranslational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure-activity relationship of this series of compounds Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development. To further elaborate the structure-activity relationship of selective JMJD3 inhibitors and to explore the novel chelating groups for Fe(II) ion, the authors initialized a medicinal chem. modification based on the GSK-J1 structure. Finally, the authors found that several compounds bearing different chelating groups showed similar activities with respect to GSK-J1 and excellent metabolic stability in liver microsomes. The Et ester prodrugs of these inhibitors also showed a better activity than GSK-J4 for inhibition of TNF-伪 production in LPS-stimulated murine macrophage cell line Raw 264.7 cells. Taking together, the current study not only discovered alternative potent JMJD3 inhibitors, but also can benefit other researchers to design new series of Jumonji demethylase inhibitors based on the identified chelating groups. 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: 1373422-53-7Product Details of 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. 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.Product Details of 1373422-53-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The histone demethylase KDM6B fine-tunes the host response to Streptococcus pneumoniae was written by Connor, Michael G.;Camarasa, Tiphaine M. N.;Patey, Emma;Rasid, Orhan;Barrio, Laura;Weight, Caroline M.;Miller, Daniel P.;Heyderman, Robert S.;Lamont, Richard J.;Enninga, Jost;Hamon, Melanie A.. And the article was included in Nature Microbiology in 2021.SDS of cas: 1373423-53-0 The following contents are mentioned in the article:

Streptococcus pneumoniae is a natural colonizer of the human respiratory tract and an opportunistic pathogen. Although epithelial cells are among the first to encounter pneumococci, the cellular processes and contribution of epithelial cells to the host response are poorly understood. Here, we show that a S. pneumoniae serotype 6B ST90 strain, which does not cause disease in a murine infection model, induces a unique NF-魏B signature response distinct from an invasive-disease-causing isolate of serotype 4 (TIGR4). This signature is characterized by activation of p65 and requires a histone demethylase KDM6B. We show, molecularly, that the interaction of the 6B strain with epithelial cells leads to chromatin remodelling within the IL-11 promoter in a KDM6B-dependent manner, where KDM6B specifically demethylates histone H3 lysine 27 di-Me. Remodelling of the IL-11 locus facilitates p65 access to three NF-魏B sites that are otherwise inaccessible when stimulated by IL-1尾 or TIGR4. Finally, we demonstrate through chem. inhibition of KDM6B with GSK-J4 inhibitor and through exogenous addition of IL-11 that the host responses to the 6B ST90 and TIGR4 strains can be interchanged both in vitro and in a murine model of infection in vivo. Our studies therefore reveal how a chromatin modifier governs cellular responses during infection. 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. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. 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.SDS of cas: 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of demethylase KDM6B sensitizes diffuse large B-cell lymphoma to chemotherapeutic drugs was written by Mathur, Rohit;Sehgal, Lalit;Havranek, Ondrej;Koehrer, Stefan;Khashab, Tamer;Jain, Neeraj;Burger, Jan A.;Neelapu, Sattva S.;Davis, R. Eric;Samaniego, Felipe. And the article was included in Haematologica in 2017.COA of Formula: C24H27N5O2 The following contents are mentioned in the article:

Histone methylation and demethylation regulate B-cell development, and their deregulation correlates with tumor chemoresistance in diffuse large B-cell lymphoma, limiting cure rates. Since histone methylation status correlates with disease aggressiveness and relapse, we investigated the therapeutic potential of inhibiting histone 3 Lys27 demethylase KDM6B, in vitro, using the small mol. inhibitor GSK-J4. KDM6B is overexpressed in the germinal center B-cell subtype of diffuse large B-cell lymphoma, and higher KDM6B levels are associated with worse survival in patients with diffuse large B-cell lymphoma treated with R-CHOP. GSK-J4-induced apoptosis was observed in five (SU-DHL-6, OCI-Ly1, Toledo, OCI-Ly8, SU-DHL-8) out of nine germinal center B-cell diffuse large B-cell lymphoma cell lines. Treatment with GSK-J4 predominantly resulted in downregulation of B-cell receptor signaling and BCL6. Cell lines expressing high BCL6 levels or CREBBP/EP300 mutations were sensitive to GSK-J4. Our results suggest that B-cell receptor-dependent downregulation of BCL6 is responsible for GSK-J4-induced cytotoxicity. Furthermore, GSK-J4-mediated inhibition of KDM6B sensitizes germinal center B-cell diffuse large B-cell lymphoma cells to chemotherapy agents that are currently utilized in treatment regimens for diffuse large B-cell lymphoma. 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. 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: C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas was written by Yabe, Shinichiro;Alexenko, Andrei P.;Amita, Mitsuyoshi;Yang, Ying;Schust, Danny J.;Sadovsky, Yoel;Ezashi, Toshihiko;Roberts, R. Michael. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2016.Reference of 219580-11-7 The following contents are mentioned in the article:

Human embryonic stem cells (ESCs) readily commit to the trophoblast lineage after exposure to bone morphogenetic protein-4 (BMP-4) and two small compounds, an activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83-01/PD173074; BAP treatment). During differentiation, areas emerge within the colonies with the biochem. and morphol. features of syncytiotrophoblast (STB). Relatively pure fractions of mononucleated cytotrophoblast (CTB) and larger syncytial sheets displaying the expected markers of STB can be obtained by differential filtration of dispersed colonies through nylon strainers. RNA-seq anal. of these fractions has allowed them to be compared with cytotrophoblasts isolated from term placentas before and after such cells had formed syncytia. Although it is clear from extensive gene marker anal. that both ESC- and placenta-derived syncytial cells are trophoblast, each with the potential to transport a wide range of solutes and synthesize placental hormones, their transcriptome profiles are sufficiently dissimilar to suggest that the two cell types have distinct pedigrees and represent functionally different kinds of STB. We propose that the STB generated from human ESCs represents the primitive syncytium encountered in early pregnancy soon after the human trophoblast invades into the uterine wall. 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: 219580-11-7Reference 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 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.Reference of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Role of JMJD3 Demethylase and Its Inhibitor GSK-J4 in Regulation of MGMT, TRA2A, RPS6KA2, and U2AF1 Genes in Prostate Cancer Cell Lines was written by Sanchez, Anna;El Ouardi, Driss;Houfaf Khoufaf, Fatma Zohra;Idrissou, Mouhamed;Boisnier, Tiphanie;Penault-Llorca, Frederique;Bignon, Yves-Jean;Guy, Laurent;Bernard-Gallon, Dominique. And the article was included in OMICS in 2020.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:

To provide evidence on involvement of JMJD3 demethylase in prostate tumor progression, & particularly on MGMT, TRA2A, RPS6KA2, & U2AF1 candidate gene expressions, anal. of H3K27me3 enrichment was performed by chromatin immunoprecipitation (ChIP)quant. polymerase chain reaction (qPCR) after inhibition of JMJD3 by GSK-J4 in prostate cancer cell lines. Subsequently, reverse transcription (RT)-qPCR conducted after inhibition of JMJD3 by siRNA/GSK-J4 inhibitor demonstrating its demethylase activity on expression of studied genes. In addn, inhibition of JMJD3 by siRNA was validated by Western blotting. Results: gene expression by RTqPCR anal. after inhibition of JMJD3 by siRNA & chem. inhibition by GSK-J4. JMJD3 inhibition by GSK-J4 exhibited non-vital decrease in JMJD3 expression in the 3 cell lines LNCaP, DU-145 & PC-3. The mRNA anal. confirmed that enrichment in H3K27me3 on target genes, led to an inhibition of MGMT, TRA2A, RPS6KA2, & U2AF1 exprsn, affirming H3K27me3 as a repressive epigenetic marker. Conclusion: The data anal. emphasized the link between JMJD3 and regulation of these genes in prostate cancer cell lines. JMJD3, regulated in vitro by siRNA/GSK-J4, making JMJD3 a potential therapeutic target. In future, it would be interesting to see effect of JMJD3 inhibition on those genes in vivo. 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. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. 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.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

Forskolin potentiates the effects of GSKJ4 in human acute myeloid leukemia cells through protein kinase A pathway was written by Illiano, Michela;Conte, Mariarosaria;Sapio, Luigi;Nebbioso, Angela;Spina, Annamaria;Altucci, Lucia;Naviglio, Silvio. And the article was included in Pharmakeutike in 2019.Category: pyrimidines The following contents are mentioned in the article:

Forskolin is a natural cAMP elevating agent that is emerging as one of the most promising mols. for its potential use in cancer therapy. The epigenetic marks play a relevant role in several cancer types, including in leukemia. In particular, GSKJ4 has been recently demonstrated to act as a potent proliferation inhibitor in many tumor cell lines. Due to the failure of the single agent therapy, recently the chemotherapy combination has received more attention in order to increase the therapeutic index and to reduce the side effects. In this scenario, naturally occurring mols. represent the ideal candidates to investigate cooperative responses with conventional and new antineoplastic drugs. Here, we investigate the capability of forskolin to potentiate the effects of GSKJ4 in human leukemia U937 cells. We provide evidence that forskolin markedly sensitizes GSKJ4-induced antiproliferative effects through apoptosis induction (caspase-3 activation and PARP cleavage). In addition, we demonstrate that this phenomenon is mediated by cAMP elevation and Protein Kinase A (PKA) involvement, as indicated by the use of PKA inhibitor (KT-5720). In conclusion, our findings provide initial evidence about the efficacy of forskolin/GSKJ4 combination in leukemia cells and suggest a new possible therapeutic approach for AML treatment. 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: 1373423-53-0Category: pyrimidines).

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. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations was written by Traer, Elie;Javidi-Sharifi, Nathalie;Agarwal, Anupriya;Dunlap, Jennifer;English, Isabel;Martinez, Jacqueline;Tyner, Jeffrey W.;Wong, Melissa;Druker, Brian J.. And the article was included in Blood in 2014.COA of Formula: C28H41N7O3 The following contents are mentioned in the article:

Development of resistance to kinase inhibitors remains a clin. challenge. Kinase domain mutations are a common mechanism of resistance in chronic myeloid leukemia (CML), yet the mechanism of resistance in the absence of mutations remains unclear. We tested proteins from the bone marrow microenvironment and found that FGF2 promotes resistance to imatinib in vitro. Fibroblast growth factor 2 (FGF2) was uniquely capable of promoting growth in both short- and long-term assays through the FGF receptor 3/RAS/c-RAF/mitogen-activated protein kinase pathway. Resistance could be overcome with ponatinib, a multikinase inhibitor that targets BCR-ABL and FGF receptor. Clin., we identified CML patients without kinase domain mutations who were resistant to multiple ABL kinase inhibitors and responded to ponatinib treatment. In comparison to CML patients with kinase domain mutations, these patients had increased FGF2 in their bone marrow when analyzed by immunohistochem. Moreover, FGF2 in the marrow decreased concurrently with response to ponatinib, further suggesting that FGF2-mediated resistance is interrupted by FGF receptor inhibition. These results illustrate the clin. importance of ligand-induced resistance to kinase inhibitors and support an approach of developing rational inhibitor combinations to circumvent resistance. 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 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.COA of Formula: C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia