Targeted inhibition of KDM6 histone demethylases eradicates tumor-initiating cells via enhancer reprogramming in colorectal cancer was written by Zhang, Junbao;Ying, Ying;Li, Meiqi;Wang, Maolin;Huang, Xiaoyan;Jia, Min;Zeng, Junhui;Ma, Canjie;Zhang, Yixiang;Li, Chen;Wang, Xiaomei;Shu, Xing-Sheng. And the article was included in Theranostics in 2020.COA of Formula: C24H27N5O2 The following contents are mentioned in the article:
Tumor-initiating cells (TICs) maintain heterogeneity within tumors and seed metastases at distant sites, contributing to therapeutic resistance and disease recurrence. In colorectal cancer (CRC), strategy that effectively eradicates TICs and is of potential value for clin. use still remains in need. The anti-tumorigenic activity of a small-mol. inhibitor of KDM6 histone demethylases named GSK-J4 in CRC was evaluated by in vitro assays and in vivo imaging of xenografted tumors. Sphere formation, flow cytometry anal. of cell surface markers and intestinal organoid formation were performed to examine the impact of GSK-J4 on TIC properties. Transcriptome anal. and global profiling of H3K27ac, H3K27me3, and KDM6A levels by ChIP-seq were conducted to elucidate how KDM6 inhibition reshapes epigenetic landscape and thereby eliminating TICs. GSK-J4 alleviated the malignant phenotypes of CRC cells in vitro and in vivo, sensitized them to chemotherapeutic treatment, and strongly repressed TIC properties and stemness-associated gene signatures in these cells. Mechanistically, KDM6 inhibition induced global enhancer reprogramming with a preferential impact on super-enhancer-associated genes, including some key genes that control stemness in CRC such as ID1 . Besides, expression of both Kdm6a and Kdm6b was more abundant in mouse intestinal crypt when compared with upper villus and inhibition of their activities blocked intestinal organoid formation. Finally, we unveiled the power of KDM6B in predicting both the overall survival outcome and recurrence of CRC patients. Our study provides a novel rational strategy to eradicate TICs through reshaping epigenetic landscape in CRC, which might also be beneficial for optimizing current therapeutics. 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