Critical role of the fibroblast growth factor signalling pathway in Ewing’s sarcoma octamer-binding transcription factor 4-mediated cell proliferation and tumorigenesis was written by Kim, Junghoon;Kim, Hyo Sun;Shim, Jung-Jae;Lee, Jungwoon;Kim, Ah-young;Kim, Jungho. And the article was included in FEBS Journal in 2019.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:
Certain bone and soft tissue (BST) tumors harbor a chromosomal translocation [t(6;22)(p21;q12)], which fuses the Ewing’s sarcoma (EWS) gene at 22q12 with the octamer-binding transcription factor 4 (Oct-4) gene at 6p21, resulting in the chimeric EWS-Oct-4 protein that possesses high transactivation ability. Although abnormal activation of signalling pathways can lead to human cancer development, the pathways underlying these processes in human BST tumors remain poorly explored. Here, we investigated the functional significance of fibroblast growth factor (FGF) signalling in human BST tumors. To identify the gene(s) involved in the FGF signalling pathway and potentially regulated by EWS-Oct-4 (also called EWS-POU5F1), we performed RNA-Seq anal., electrophoretic mobility shift assays, chromatin immunoprecipitation assays, and xenograft assays. Treating GBS6 or ZHBTc4 cells-expressing EWS-Oct-4 with the small mol. FGF receptor (FGFR) inhibitors PD173074, NVPBGJ398, ponatinib, and dovitinib suppressed cellular proliferation. Gene expression anal. revealed that, among 22 Fgf and four Fgfr family members, Fgf-4 showed the highest upregulation (by 145-fold) in ZHBTc4 cells-expressing EWS-Oct-4. Computer-assisted anal. identified a putative EWS-Oct-4-binding site at +3017/+3024, suggesting that EWS-Oct-4 regulates Fgf-4 expression in human BST tumors. Fgf-4 enhancer constructs showed that EWS-Oct-4 transactivated the Fgf-4 gene reporter in vitro, and that overexpression of EWS-Oct-4 stimulated endogenous Fgf-4 gene expression in vivo. Finally, PD173074 significantly decreased tumor volume in mice. Taken together, these data suggest that FGF-4 signalling is involved in EWS-Oct-4-mediated tumorigenesis, and that its inhibition impairs tumor growth in vivo significantly. 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. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. 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.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