Day: November 22, 2022

An IFNγ/STAT1/JMJD3 axis induces ZEB1 expression and promotes aggressiveness in lung adenocarcinoma was written by Yang, Jianjian;Wang, Xue;Huang, Bing;Liu, Rong;Xiong, Hui;Ye, Fan;Zeng, Chenxi;Fu, Xiangning;Li, Lequn. And the article was included in Molecular Cancer Research in 2021.Computed Properties of C24H27N5O2 The following contents are mentioned in the article:

Active IFNγ signaling is a common feature of tumors responding to PD-1 checkpoint blockade. IFNγ exhibits both anti- and protumor activities. Here, we show that the treatment of lung adenocarcinoma cells with IFNγ led to a rapid increase of ZEB1 expression and a significant change in epithelial-to-mesenchymal transition (EMT)-associated gene expression pattern. Moreover, functional analyses show that IFNγ promoted cell migration in vitro and metastasis in vivo. We demonstrate that ZEB1 is required for IFNγ-promoted EMT, cell migration, and metastasis, as RNAi-mediated knockdown of ZEB1 abrogated EMT, cell migration, and metastasis induced by IFNγ. We show that IFNγ induced upregulation of JMJD3 significantly reduced H3K27 trimethylation in the promoter of the ZEB1 gene, which led to activation of ZEB1 gene transcription. IFNγ-induced JMJD3 expression was JAK1/2-STAT1 dependent. Inhibition of JMJD3 abrogated IFNγ-induced ZEB1 expression. IFNγ-induced ZEB1 also reduced miR-200 expression. Downregulation of ZEB1 increased miR-200 expression, which led to a reduction of PD-L1 expression induced by IFNγ. It is worth noting that knockdown of ZEB1 did not affect IFNγ-mediated antiproliferation and induction of CXCL9 and CXCL10. Thus, downregulation of ZEB1 may prevent the protumor activity of IFNγ while retaining its antitumor function. This study expands our understanding of IFNγ-mediated signaling and helps to identify therapeutic targets to improve current immunotherapies. 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. 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.Computed Properties of C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically regulating the PTEN/AKT signaling pathway was written by Wang, Lihui;Dong, Xiaoyu;Ren, Yong;Luo, Juanjuan;Liu, Pei;Su, Dongsheng;Yang, Xiaojun. And the article was included in Cell Death & Disease in 2018.Application of 1373422-53-7 The following contents are mentioned in the article:

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Epigenetic alterations have been shown to be involved in NSCLC oncogenesis; however, their function in EGFR-TKI resistance remains uncharacterized. Here, we found that an EHMT2 inhibitor, UNC0638, can significantly inhibit cell growth and induce apoptosis in EGFR-TKI-resistant NSCLC cells. Addnl., we also found that EHMT2 expression and enzymic activity levels were elevated in EGFR-TKI-resistant NSCLC cells. Moreover, we determined that genetic or pharmacol. inhibition of EHMT2 expression enhanced TKI sensitivity and suppressed migration and tumor sphere formation in EGFR-TKI-resistant NSCLC cells. Further investigation revealed that EHMT2 contributed to PTEN transcriptional repression and thus facilitated AKT pathway activation. The neg. relationship between EHMT2 and PTEN was confirmed by our clin. study. Furthermore, we determined that combination treatment with the EHMT2 inhibitor and Erlotinib resulted in enhanced antitumor effects in a preclin. EGFR-TKI-resistance model. We also found that high EHMT2 expression along with low PTEN expression can predict poor overall survival in patients with NSCLC. In summary, our findings showed that EHMT2 facilitated EGFR-TKI resistance by regulating the PTEN/AKT pathway in NSCLC cells, suggesting that EHMT2 may be a target in the clin. treatment of EGFR-TKI-resistant NSCLC. 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: 1373422-53-7Application 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. 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. 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 of 1373422-53-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing was written by Davis, Frank M.;denDekker, Aaron;Joshi, Amrita D.;Wolf, Sonya J.;Audu, Christopher;Melvin, William J.;Mangum, Kevin;Riordan, Mary O.;Kunkel, Steven L.;Gallagher, Katherine A.. And the article was included in European Journal of Immunology in 2020.SDS of cas: 1373423-53-0 The following contents are mentioned in the article:

Chronic macrophage inflammation is a hallmark of (T2D) and linked to the development of secondary diabetic complications. T2D is characterized by excess concentrations of saturated fatty acids (SFA) that activate innate immune inflammatory responses, however, mechanism(s) by which SFAs control inflammation is unknown. Using monocyte-macrophages isolated from human blood and murine models, we demonstrate that (C16:0), the most abundant circulating SFA in T2D, increases expression of the histone demethylase, Jmjd3. Upregulation of Jmjd3 results in removal of the repressive (H3K27me3) mark on NFκB-mediated inflammatory gene promoters driving macrophage-mediated inflammation. We identify that the effects of palmitate are fatty acid specific, as laurate (C12:0) does not regulate Jmjd3 and the associated inflammatory profile. Further, palmitate-induced Jmjd3 expression is controlled via TLR4/MyD88-dependent signaling mechanism, where genetic depletion of TLR4 (Tlr4^-/-) or MyD88 (MyD88^-/-) negated the palmitate-induced changes in Jmjd3 and downstream NFκB-induced inflammation. Pharmacol. inhibition of Jmjd3 using a small mol. inhibitor (GSK-J4) reduced macrophage inflammation and improved diabetic wound healing. Together, we conclude that palmitate contributes to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy may represent a novel treatment for nonhealing diabetic wounds. 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. 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.SDS of cas: 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A transcriptomic dataset used to derive biomarkers of chemically induced histone deacetylase inhibition (HDACi) in human TK6 cells was written by Cho, Eunnara;Williams, Andrew;Yauk, Carole L.. And the article was included in Data in Brief in 2021.Application of 1373423-53-0 The following contents are mentioned in the article:

Transcriptomic biomarkers facilitate mode of action anal. of toxicants by detecting specific patterns of gene expression perturbations. We identified an 81-gene transcriptomic biomarker of histone deacetylase inhibitors (HDACi) using whole transcriptome data sets of TK6 human lymphoblastoid cells generated by Templated Oligo-Sequencing (TempO-Seq) after 4 h of exposure to 20 reference compounds (10 HDACi and 10 non-HDACi) [1]. The biomarker, named TGx-HDACi, was derived using the nearest shrunken centroid (NSC) method and can distinguish HDACi from non-HDACi compounds based on the expression pattern across the 81 genes. The classification capability of TGx-HDACi was evaluated by NSC probability anal. of 11 external validation compounds (4 HDACi and 7 non-HDACi) with a probability cut-off of 90%. Thus far, TGx-HDACi has demonstrated 100% accuracy in classifying the reference and validation compounds as HDACi or non-HDACi. Of the 81 TGx-HDACi genes, 19 genes are part of the S1500+ gene panel containing 2753 genes, developed for toxicol. assessments [2]. Herein, we assessed the classification performance of the biomarker with this reduced gene set to determine if TGx-HDACi can be applied to analyze S1500+ gene expression profiles. The 20 reference compounds and 11 validation compounds were correctly classified as HDACi or non-HDACi by the NSC probability anal., principal component anal., and hierarchical clustering based on the expression of the 19 genes, demonstrating 100% accuracy. 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 pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. 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

Combined action of FOXO1 and superoxide dismutase 3 promotes MDA-MB-231 cell migration was written by Kamiya, Tetsuro;Yamaguchi, Yuji;Oka, Manami;Hara, Hirokazu. And the article was included in Free Radical Research in 2022.COA of Formula: C24H27N5O2 The following contents are mentioned in the article:

Superoxide dismutase 3 (SOD3), one of SOD isoenzymes, maintains extracellular redox homeostasis through the dismutation reaction of superoxide. Loss of SOD3 in tumor cells induces oxidative stress and exacerbates tumor progression; however, interestingly, overexpression of SOD3 also promotes cell proliferation through the production of hydrogen peroxide. In this study, we investigated the functional role of SOD3 in human breast cancer MDA-MB-231 cell migration and the mol. mechanisms involved in high expression of SOD3 in MDA-MB-231 cells and human monocytic THP-1 cells. The level of histone H3 trimethylation at lysine 27 (H3K27me3), a marker of gene silencing, was decreased in 12-O-tetra-decanoylphorbol-13-acetate (TPA)-treated THP-1 cells. Also, that reduction was observed within the SOD3 promoter region. We then investigated the involvement of H3K27 demethylase JMJD3 in SOD3 induction. The induction of SOD3 and the reduction of H3K27me3 were inhibited in the presence of JMJD3 inhibitor, GSK-J4. Addnl., it was first determined that the knockdown of the transcription factor forkhead box O1 (FOXO1) significantly suppressed TPA-elicited SOD3 induction. FOXO1-mediated SOD3 downregulation was also observed in MDA-MB-231 cells, and knockdown of FOXO1 and SOD3 suppressed cell migration. Our results provide a novel insight into epigenetic regulation of SOD3 expression in tumor-associated cells, and high expression of FOXO1 and SOD3 would participate in the migration of MDA-MB-231 cells. 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 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.COA of Formula: C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Pyrimidines. LXIV. Synthesis of 4-Methyl-5-ethyleytosine was written by Johnson, Treat B.;Bailey, George C.. And the article was included in Journal of the American Chemical Society in 1913.Application of 39083-15-3 The following contents are mentioned in the article:

2-Thio-4-methyl-5-ethyl-6-oxypyrimidine, from CS(NH₂)₂, AcCHEtCO₂Et and Na in alc. 3-4 hrs. on the H₂O bath, prisms, m. 212° (yield, 60%); its Na. salt in alc. gives with PhCH₂Cl the 2-benzyltnercapto derivative, blocks, m. 160°; 2-ethylmercapto derivative, m. 138°, converted by PCl₆ at 100° after 10-12 hrs. into 2-ethylmercapto-4-methyl-5-ethyl-6-chloropyrimidine, b_23-1 177-80°, and by PhNH₂ in hot alc. into 2-anilino-4-methyl-5-ethyl-6-oxypyrimidine, m. 195°, while alc. NH₃, 3 hrs. at 150-60, instead of PhNH₂ gives the 2-amino compound, Minute Prisms, m. 281-20 (decompose); hydrobromide, needles, m. 160-75°, depending on the rate of heating; hydrochloride, apparently seps. with 1 H₂O, shrivels 80°, m. 11.5°. 2-Ethylmercapto-4-methyl-5-etlzyl-6-aminopyrimidine, from the above 6-Cl compound and alc. NH₃ at 140-50°, stout blocks, m. 89-91°, hydrolyzed by b. concentrate HCl to the hydrochloride, powder, decompose 125°, of 2-oxy-4-methyl-5-ethyl-6-aminopyrimidine (methylethylcylosine), blocks or rectangular prisms, m. 295° (decompose); hydrobromide, blocks, dedomp. about 260°. 4-Methyl-5-ethyluracil is obtained quant. by b. 2-ethylmereapto-4-methyl-5-ethyl-6-oxypyrimidine with 2 parts of ClCH₂CO₂H in H₂O. 2-Diphenylmethylmercapto-4-methyl-6-oxypyrimidine, from Ph₂CHBr, 2-thio-4-methyluracil and Na in alc., m. 214. This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3Application of 39083-15-3).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) 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.Application of 39083-15-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells was written by Grygielewicz, Paulina;Dymek, Barbara;Bujak, Anna;Gunerka, Pawel;Stanczak, Aleksandra;Lamparska-Przybysz, Monika;Wieczorek, Maciej;Dzwonek, Karolina;Zdzalik, Daria. And the article was included in Gastric Cancer in 2016.Formula: C28H41N7O3 The following contents are mentioned in the article:

Background: Up to 10 % of primary gastric cancers are characterized by FGFR2 amplification, and fibroblast growth factor receptor (FGFR) inhibitors may represent therapeutic agents for patients with these malignancies. However, long-term benefits of the treatment might be limited owing to the occurrence of drug resistance. Methods: To investigate the mechanisms of resistance to selective FGFR inhibitors, we established three FGFR2-amplified SNU-16 gastric cancer cell lines resistant to AZD4547, BGJ398, and PD173074, resp. Results: The resistant cell lines (SNU-16R) demonstrated changes characteristic of epithelial-to-mesenchymal transition (EMT). In addition, they displayed loss of expression of FGFR2 and other tyrosine kinase receptors concurrent with activation of downstream signaling proteins and upregulation of the transforming growth factor β (TGF-β) level. However, treatment of parental SNU-16 cells with TGF-β₁ did not evoke EMT, and pharmacol. inhibition of TGF-β receptor I was not sufficient to reverse EMT changes in the resistant cells. Finally, we showed that the SNU-16R cell lines were sensitive to the human epidermal growth factor receptor 2 inhibitor mubritinib and the heat shock protein 90 inhibitor AUY922. Conclusion: In conclusion, we provide exptl. evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these 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: 219580-11-7Formula: 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. 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.Formula: C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cancer genomics and genetics of FGFR2 (Review) was written by Katoh, Masaru. And the article was included in International Journal of Oncology in 2008.Application In Synthesis of 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:

A review. FGFR2 gene encodes FGFR2b in epithelial cells, and FGFR2c in mesenchymal cells. FGFR2b is a high affinity receptor for FGF1, FGF3, FGF7, FGF10 and FGF22, while FGFR2c for FGF1, FGF2, FGF4, FGF6, FGF9, FGF16 and FGF20. Here genomics and genetics of FGFR2, and therapeutics targeted to FGFR2 will be reviewed. Single nucleotide polymorphisms (SNPs) of FGFR2 are associated with increased risk of breast cancer. Gene amplification or missense mutation of FGFR2 occurs in gastric cancer, lung cancer, breast cancer, ovarian cancer, and endometrial cancer. Genetic alterations of FGFR2 induce aberrant FGFR2 signaling activation due to release of FGFR2 from autoinhibition, or creation of FGF signaling autocrine loop. Class switch of FGFR2b to FGFR2c is associated with more malignant phenotype. FGF and canonical WNT signals synergize during mammary carcinogenesis, but counteract during osteogenesis and adipogenesis. Among PD173074, SU5402, and AZD2171 functioning as FGFR inhibitors, AZD2171 is the most promising anti-cancer drug. Cancer genomics and genetics are utilized to predict cancer-driving pathway for therapeutic optimization. FGFR2ome is defined as a complete data set of SNP, copy number variation (CNV), missense mutation, gene amplification, and predominant isoform of FGFR2. FGFR2ome analyses in patients with several tumor types among various populations should be carried out to establish integrative database of FGFR2 for the rational clin. application of FGFR2-targeted cancer therapy. 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: 219580-11-7Application In Synthesis of 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. 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 In Synthesis of 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

Integrative and Personalized QSAR Analysis in Cancer by Kernelized Bayesian Matrix Factorization was written by Ammad-ud-din, Muhammad;Georgii, Elisabeth;Gonen, Mehmet;Laitinen, Tuomo;Kallioniemi, Olli;Wennerberg, Krister;Poso, Antti;Kaski, Samuel. And the article was included in Journal of Chemical Information and Modeling in 2014.Product Details of 219580-11-7 The following contents are mentioned in the article:

With data from recent large-scale drug sensitivity measurement campaigns, it is now possible to build and test models predicting responses for more than one hundred anticancer drugs against several hundreds of human cancer cell lines. Traditional quant. structure-activity relation (QSAR) approaches focus on small mols. in searching for their structural properties predictive of the biol. activity in a single cell line or a single tissue type. We extend this line of research in two directions: (1) an integrative QSAR approach predicting the responses to new drugs for a panel of multiple known cancer cell lines simultaneously and (2) a personalized QSAR approach predicting the responses to new drugs for new cancer cell lines. To solve the modeling task, we apply a novel kernelized Bayesian matrix factorization method. For maximum applicability and predictive performance, the method optionally utilizes genomic features of cell lines and target information on drugs in addition to chem. drug descriptors. In a case study with 116 anticancer drugs and 650 cell lines, we demonstrate the usefulness of the method in several relevant prediction scenarios, differing in the amount of available information, and analyze the importance of various types of drug features for the response prediction. Furthermore, after predicting the missing values of the data set, a complete global map of drug response is explored to assess treatment potential and treatment range of therapeutically interesting anticancer drugs. 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. 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.Product Details of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors was written by Wilson, Timothy R.;Fridlyand, Jane;Yan, Yibing;Penuel, Elicia;Burton, Luciana;Chan, Emily;Peng, Jing;Lin, Eva;Wang, Yulei;Sosman, Jeff;Ribas, Antoni;Li, Jiang;Moffat, John;Sutherlin, Daniel P.;Koeppen, Hartmut;Merchant, Mark;Neve, Richard;Settleman, Jeff. And the article was included in Nature (London, United Kingdom) in 2012.Application In Synthesis of 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:

Mutationally activated kinases define a clin. validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumors harbor such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme-the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors-most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumor-cell production, paracrine contribution from tumor stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signaling output. Here, using a panel of kinase- addicted’ human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clin. implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signaling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic 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: 219580-11-7Application In Synthesis of 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. 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.Application In Synthesis of 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