Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism was written by Cribbs, Adam P.;Terlecki-Zaniewicz, Stefan;Philpott, Martin;Baardman, Jeroen;Ahern, David;Lindow, Morten;Obad, Susanna;Oerum, Henrik;Sampey, Brante;Mander, Palwinder K.;Penn, Henry;Wordsworth, Paul;Bowness, Paul;de Winther, Menno;Prinjha, Rab K.;Feldmann, Marc;Oppermann, Udo. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2020.Electric Literature of C24H27N5O2 The following contents are mentioned in the article:
T helper (Th) cells are CD4+ effector T cells that play a critical role in immunity by shaping the inflammatory cytokine environment in a variety of physiol. and pathol. situations. Using a combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A and KDM6B as central regulators of human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels of the repressive H3K27me3 chromatin mark and leads to suppression of the key transcription factor RORγt during Th17 differentiation. In mature Th17 cells, GSK-J4 induces an altered transcriptional program with a profound metabolic reprogramming and concomitant suppression of IL-17 cytokine levels and reduced proliferation. Single-cell anal. reveals a specific shift from highly inflammatory cell subsets toward a resting state upon demethylase inhibition. The root cause of the observed antiinflammatory phenotype in stimulated Th17 cells is reduced expression of key metabolic transcription factors, such as PPRC1. Overall, this leads to reduced mitochondrial biogenesis, resulting in a metabolic switch with concomitant antiinflammatory effects. These data are consistent with an effect of GSK-J4 on Th17 T cell differentiation pathways directly related to proliferation and include regulation of effector cytokine profiles. This suggests that inhibiting KDM6 demethylases may be an effective, even in the short term, therapeutic target for autoimmune diseases, including ankylosing spondylitis. 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).
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Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia