Day: November 22, 2022

Acquired Resistance of Non-Small Cell Lung Cancer Cells to MET Kinase Inhibition Is Mediated by a Switch to Epidermal Growth Factor Receptor Dependency was written by McDermott, Ultan;Pusapati, Raju V.;Christensen, James G.;Gray, Nathanael S.;Settleman, Jeff. And the article was included in Cancer Research in 2010.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:

Cancer cells harboring MET amplification display striking sensitivity to selective small mol. inhibitors of MET kinase, prompting their clin. evaluation. Similar to the experience with traditional therapeutics, most patients responding to treatment with such mol. targeted therapeutics ultimately relapse with drug-resistant disease. In this study we modeled acquired resistance to exptl. MET kinase inhibitor PF2341066 in MET-amplified non-small cell lung carcinoma (NSCLC) cell lines to identify drug resistance mechanisms that may arise in clinic. We found that activation of the epidermal growth factor receptor (EGFR) pathway emerges as a resistance mechanism in MET-amplified cells after prolonged exposure to PF2341066. Whereas combined inhibition of MET and EGFR kinases in MET-dependent NSCLC cells did not enhance their initial sensitivity to PF2341066, this combination dramatically suppressed the eventual emergence of drug-resistant clones after prolonged drug exposure. Conversely, activation of the EGFR pathway increased the yield of PF2341066-resistant clones, confirming the significance of this pathway in conferring resistance. Our findings support an intimate relationship between the EGFR and MET signaling pathways in NSCLC, and they suggest that combination treatment with MET and EGFR kinase inhibitors may be beneficial in MET-amplified NSCLC by reducing selection for drug resistant clones. Cancer Res; 70(4); 1625-34. 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. 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.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

Multikinase activity of fibroblast growth factor receptor (FGFR) inhibitors SU5402, PD173074, AZD1480, AZD4547 and BGJ398 compromises the use of small chemicals targeting FGFR catalytic activity for therapy of short-stature syndromes was written by Gudernova, Iva;Vesela, Iva;Balek, Lukas;Buchtova, Marcela;Dosedelova, Hana;Kunova, Michaela;Pivnicka, Jakub;Jelinkova, Iva;Roubalova, Lucie;Kozubik, Alois;Krejci, Pavel. And the article was included in Human Molecular Genetics in 2016.Formula: C28H41N7O3 The following contents are mentioned in the article:

Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) cause the most common genetic form of human dwarfism, achondroplasia (ACH). Small chem. inhibitors of FGFR tyrosine kinase activity are considered to be viable option for treating ACH, but little exptl. evidence supports this claim. We evaluated five FGFR tyrosine kinase inhibitors (TKIs) (SU5402, PD173074, AZD1480, AZD4547 and BGJ398) for their activity against FGFR signaling in chondrocytes. All five TKIs strongly inhibited FGFR activation in cultured chondrocytes and limb rudiment cultures, completely relieving FGFR-mediated inhibition of chondrocyte proliferation and maturation. In contrast, TKI treatment of newborn mice did not improve skeletal growth and had lethal toxic effects on the liver, lungs and kidneys. In cell-free kinase assays as well as in vitro and in vivo cell assays, none of the tested TKIs demonstrated selectivity for FGFR3 over three other FGFR tyrosine kinases. In addition, the TKIs exhibited significant off-target activity when screened against a panel of 14 unrelated tyrosine kinases. This was most extensive in SU5402 and AZD1480, which inhibited DDR2, IGF1R, FLT3, TRKA, FLT4, ABL and JAK3 with efficiencies similar to or greater than those for FGFR. Low target specificity and toxicity of FGFR TKIs thus compromise their use for treatment of ACH. Conceptually, different avenues of therapeutic FGFR3 targeting should be investigated. 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. 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.Formula: C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Small Molecule GSK-J1 Affects Differentiation of Specific Neuronal Subtypes in Developing Rat Retina was written by Raeisossadati, Reza;Movio, Marilia Ines;Walter, Lais Takata;Takada, Silvia Honda;Del Debbio, Carolina Beltrame;Kihara, Alexandre Hiroaki. And the article was included in Molecular Neurobiology in 2019.Electric Literature of C22H23N5O2 The following contents are mentioned in the article:

In this study, we focused on the role of potent histone demethylase inhibitor GSK-J1 as a blocker of Jumonji domain-containing protein 3 (Jmjd3) in early postnatal retinal development. Jmjd3 participates in different processes such as cell proliferation, apoptosis, differentiation, senescence, and cell reprogramming via demethylation of histone 3 lysine 27 trimethylation status (H3K27 me3). We observed that Jmjd3 accumulation is higher in the adult retina, which is consistent with the localization in the differentiated neurons, including ganglion cells in the retina of neonate rats. At this developmental age, we also observed the presence of Jmjd3 in undifferentiated cells. Interestingly, GSK-J1 specifically caused a significant decrease in the number of PKCa-pos. cells, which is a reliable marker of rod-on bipolar cells, showing no significant effects on the differentiation of other retinal subtypes. To our knowledge, these data provide the first evidence that in vivo pharmacol. blocking of histone demethylase by GSK-J1 affects differentiation of specific neuronal subtypes. In summary, our results indisputably revealed that the application of GSK-J1 could influence cell proliferation, maturation, apoptosis induction, and specific cell determination With this, we were able to provide evidence that this small mol. can be explored in therapeutic strategies for the abnormal development and diseases of the central nervous system. 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. 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.Electric Literature of C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A novel cell membrane affinity sample pretreatment technique for recognition and preconcentration of active components from traditional Chinese medicine was written by Bu, Yusi;He, Xiaoshuang;Hu, Qi;Wang, Cheng;Xie, Xiaoyu;Wang, Sicen. And the article was included in Scientific Reports in 2017.Safety 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:

We describe a novel biomembrane affinity sample pretreatment technique to quickly screen and preconc. active components from traditional Chinese medicine (TCM), which adopts cell membrane coated silica particles (CMCSPs) as affinity ligands which benefit the biomembrane’s ability to maximize simulation of drug-receptor interactions in vivo. In this study, the prepared CMCSPs formed by irreversible adsorption of fibroblast growth factor receptor 4 (FGFR4) cell membrane on the surface of silica were characterized using different spectroscopic and imaging instruments. Drug binding experiments showed the excellent adsorption rate and adsorption capacity of FGFR4/CMCSPs compared with non-coated silica particles. The FGFR4/CMCSPs were used as solid-phase extraction sorbents to pretreat the TCM Aconitum szechenyianum Gay. The resultant FGFR4/CMCSPs exhibited good performance. In addition, high selectivity and recognition ability of the FGFR4/CMCSPs were determined by selectivity experiments Four alkaloid were screened and identified, one of these alkaloid, napellonine, showed favorable anti-tumor activity in preliminary pharmacol. verification trials including cell proliferation and mol. docking assays. The proposed cell membrane affinity sample pretreatment method is a reliable, effective and time-saving method for fast screening and enriching active compounds and can be extended to pretreat other TCMs as leading compounds resources. 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: 219580-11-7Safety 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 ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. 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.Safety 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

FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage was written by Okada, Takeshi;Enkhjargal, Budbazar;Travis, Zachary D.;Ocak, Umut;Tang, Jiping;Suzuki, Hidenori;Zhang, John H.. And the article was included in Molecular Neurobiology in 2019.Computed Properties of C28H41N7O3 The following contents are mentioned in the article:

We investigated the anti-apoptotic property of fibroblast growth factor (FGF)-2 after SAH in rats. A total of 289 rats underwent endovascular perforation to induce SAH or sham operation. Three dosages (3, 9, or 27 ug) of recombinant FGF-2 (rFGF-2) or vehicle was administered intranasally to rats 30 min after SAH induction. The pan-FGF receptor (FGFR) inhibitor PD173074 or vehicle was administered intracerebroventricularly (i.c.v.) 1 h before modeling, in addition to rFGF-2 treatment. Small interfering RNA (siRNA) for FGFR1 and FGFR3 or scrambled siRNA was administered i.c.v. 48 h before SAH induction in addition to rFGF-2 treatment. Anti-FGF-2 neutralizing antibody or normal mouse IgG (IgG) was administered i.c.v. 1 h before SAH model. A rFGF-2 treatment improved motor skill learning and spatial memory and increased the number of surviving neurons postinjury to 28 days after SAH. PD173074 abolished the anti-apoptotic effects of rFGF-2 via suppression of the expression of PI3k, phosphorylated Akt (p-Akt), and Bcl-2 leading to enhancement of the expression of Bax. FGFR3 siRNA worsened neurobehavioral function and suppressed the expression of PI3k, p-Akt, and Bcl-2 rather than FGFR1 siRNA in SAH rats treated with rFGF-2. Anti-FGF-2 neutralizing antibody suppressed the expression of PI3k and p-Akt after SAH. FGF-2 may be a promising therapy to reduce post-SAH neuronal apoptosis via activation of the FGFR3/PI3k/Akt signaling pathway. 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. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Computed Properties of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

HMGN1 plays a significant role in CRLF2 driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort was written by Page, Elyse C.;Heatley, Susan L.;Eadie, Laura N.;McClure, Barbara J.;de Bock, Charles E.;Omari, Sofia;Yeung, David T.;Hughes, Timothy P.;Thomas, Paul Q.;White, Deborah L.. And the article was included in Oncogene in 2022.Quality Control 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:

The genetic basis of the predisposition for Down Syndrome (DS) patients to develop cytokine receptor-like factor 2 rearranged (CRLF2r) acute lymphoblastic leukemia (ALL) is currently unknown. Genes located on chromosome 21 and expressed in hematopoietic cells are likely candidates for investigation of CRLF2r DS-ALL pathogenesis. We explored the high-mobility group nucleosome-binding protein 1 (HMGN1), located in the DS critical region, in an inducible CRISPR/Cas9 knockout (KO) xenograft model to assess the effect of HMGN1 loss of function on the leukemic burden. We demonstrated HMGN1 KO-mitigated leukemic phenotypes including hepatosplenomegaly, thrombocytopenia, and anemia, commonly observed in leukemia patients, and significantly increased survival in vivo. HMGN1 overexpression in murine stem cells and Ba/F3 cells in vitro, in combination with P2RY8-CRLF2, resulted in cytokine-independent transformation and upregulation of cell signaling pathways associated with leukemic development. Finally, in vitro screening demonstrated successful targeting of P2RY8-CRLF2 and HMGN1 co-expressing cell lines and patient samples with fedratinib (JAK2 inhibitor), and GSK-J4 (demethylase inhibitor) in combination. Together, these data provide critical insight into the development and persistence of CRLF2r DS-ALL and identify HMGN1 as a potential therapeutic target to improve outcomes and reduce toxicity in this high-risk cohort of young 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: 1373423-53-0Quality Control 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. 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.Quality Control 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

UTX-1 regulates Tat-induced HIV-1 transactivation via changing the methylated status of histone H3 was written by Zhang, Hong-Sheng;Du, Guang-Yuan;Liu, Yang;Zhang, Zhong-Guo;Zhou, Zhen;Li, Hu;Dai, Ke-Qing;Yu, Xiao-Ying;Gou, Xiao-Meng. And the article was included in International Journal of Biochemistry & Cell Biology in 2016.Category: pyrimidines The following contents are mentioned in the article:

Epigenetic modifications are thought to be important for gene expression changes during HIV-1 transcription and replication. The removal of histone H3 lysine27 (H3K27) trimethylation mark by UTX-1 is important for the robust induction of many specific genes during Tat-mediated HIV-1 transactvation. We found that UTX-1 enzymic activity is needed for Tat to remove a repressive mark H3K27me3 in the HIV-1 long terminal repeat (LTR). UTX-1 converted the chromatin structure to a more transcriptionally active state by up-regulation of H3K4 methylation and down-regulation of H3K27 methylation on the specific regions of HIV-1 LTR. The increase in H3K27me3 and the decrease in H3K4me3 induced by UTX-1 knockdown was detected on the HIV-1 LTR, but not by control siRNA. Addnl., UTX-1 promotes HIV-1 gene expression by enhancing both the NF-κB p65’s nuclear translocation and its p65 binding to HIV-1 LTR. And we further demonstrated that H3K27 demethylase activity was required for increased HIV-1 transactivation induced by UTX-1. Together, our data reveal key roles for UTX-1 in a timely transition from poised to active chromatin in HIV-1 LTR during HIV-1 transcription and a fundamental mechanism by which a H3K27 demethylase triggers tissue-specific chromatin changes. Our findings provide a mechanistic link between UTX-1 and enhanced HIV-1 replication, and suggest that targeting at epigenetic mechanism may have a therapeutic benefit for HIV-1 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: 1373423-53-0Category: 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 ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

H19-dependent transcriptional regulation of β3 and β4 integrins upon estrogen and hypoxia favors metastatic potential in prostate cancer was written by Bacci, Lorenza;Aiello, Aurora;Ripoli, Cristian;Loria, Rossella;Pugliese, Dario;Pierconti, Francesco;Rotili, Dante;Strigari, Lidia;Pinto, Francesco;Bassi, Pier Francesco;Mai, Antonello;Grassi, Claudio;Pontecorvi, Alfredo;Falcioni, Rita;Farsetti, Antonella;Nanni, Simona. And the article was included in International Journal of Molecular Sciences in 2019.Category: pyrimidines The following contents are mentioned in the article:

Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion mols.’expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR andWestern blot. The mol. mechanism was addressed by chromatin immunoprecipitations, overexpression, and silencing assays. PCa cells’ metastatic potential was analyzed by in vitro cell-cell adhesion, motility test, and trans-well invasion assay. We found that combined treatment caused a significant H19 down-regulation as compared with hypoxia. In turn, H19 acts as a transcriptional repressor of cell adhesion mols., as revealed by up-regulation of both β3 and β4 integrins and E-cadherin upon H19 silencing or combined treatment. Importantly, H19 down-regulation and β integrins induction were also observed in treated OSCs. Combined treatment increased both cell motility and invasion of PCa cells. Lastly, reduction of β integrins and invasion was achieved through epigenetic modulation of H19-dependent transcription. Our study revealed that estrogen and hypoxia transcriptionally regulate, via H19, cell adhesion mols. redirecting metastatic dissemination from EMT to a β integrin-mediated invasion. 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 ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention was written by Ho, Han Kiat;Pok, Sharon;Streit, Sylvia;Ruhe, Jens E.;Hart, Stefan;Lim, Kah Suan;Loo, Hooi Linn;Aung, Myat Oo;Lim, Seng Gee;Ullrich, Axel. And the article was included in Journal of Hepatology in 2008.Related Products of 219580-11-7 The following contents are mentioned in the article:

FGFR4, a member of the fibroblast growth factor receptor family, has been recently associated with progression of melanoma, breast and head and neck carcinoma. Given its uniquely high expression in the liver, we investigated its contributory role to hepatocellular carcinoma (HCC). We performed a comprehensive sequencing of full-length FGFR4 transcript in 57 tumor/normal HCC tissue pairs, and quantified their mRNA expressions. Notable mutations and expression patterns were correlated with patient data. Clin. significant trends were examined in in vitro models. We found eight genetic alterations including two highly frequent polymorphisms (V10I and G338R). Secretion of alpha-fetoprotein (AFP), a HCC biomarker, was increased among patients bearing homozygous Arg388 alleles. One-third of these patients exhibited increased FGFR4 mRNA expression in the matched tumor/normal tissue. Subsequent in vitro perturbation of FGFR4 signaling through both FGF19-stimulation and FGFR4 silencing confirmed a mechanistic link between FGFR4 activities and tumor aggressiveness. More importantly, inhibition of FGFR activity with PD173074 exquisitely blocked HuH7 (high FGFR4 expression) proliferation as compared to control cell lines. FGFR4 contributes significantly to HCC progression by modulating AFP secretion, proliferation and anti-apoptosis. Its frequent overexpression in patients renders its inhibition a novel and much needed pharmacol. approach against HCC. 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: 219580-11-7Related Products 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 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. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Related Products of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Therapeutically targeting head and neck squamous cell carcinoma through synergistic inhibition of LSD1 and JMJD3 by TCP and GSK-J1 was written by Zhang, Wei;Cheng, Jie;Diao, Pengfei;Wang, Dongmiao;Jiang, Hongbing;Wang, Yanling. And the article was included in British Journal of Cancer in 2020.Recommanded Product: 1373422-53-7 The following contents are mentioned in the article:

Background: The histone demethylase LSD1 is a key mediator driving tumorigenesis, which holds potential as a promising therapeutic target. However, treatment with LSD1 inhibitors alone failed to result in complete cancer regression. Methods: The synergistic effects of TCP (a LSD1 inhibitor) and GSK-J1 (a JMJD3 inhibitor) against HNSCC were determined in vitro and in preclin. animal models. Genes modulated by chem. agents or siRNAs in HNSCC cells were identified by RNA-seq and further functionally interrogated by bioinformatics approach. Integrative siRNA-mediated gene knockdown, rescue experiment and ChIP-qPCR assays were utilized to characterize the mediators underlying the therapeutic effects conferred by TCP and GSK-J1. Results: Treatment with TCP and GSK-J1 impaired cell proliferation, induced apoptosis and senescence in vitro, which were largely recapitulated by simultaneous LSD1 and JMJD3 knockdown. Combinational treatment inhibited tumor growth and progression in vivo. Differentially expressed genes modulated by TCP and GSK-J1 were significantly enriched in cell proliferation, apoptosis and cancer-related pathways. SPP1 was identified as the mediator of synergy underlying the pro-apoptosis effects conferred by TCP and GSK-J1. Co-upregulation of LSD1 and JMJD3 associated with worse prognosis in patients with HNSCC. Conclusions: Our findings revealed a novel therapeutic strategy of simultaneous LSD1 and JMJD3 inhibition against HNSCC. 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: 1373422-53-7Recommanded Product: 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. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Recommanded Product: 1373422-53-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia