Premkumar, Kavitha published the artcileIdentification of EPZ004777 and FG2216 as inhibitors of TGF-β1 induced Treg cells by screening a library of epigenetic compounds, Computed Properties of 1338466-77-5, the publication is Life Sciences (2022), 120643, database is CAplus and MEDLINE.
Regulatory T cells play an essential role in immune tolerance and homeostasis. Their long-term stability depends on epigenetic modifications and identification of small mol. modulators of Treg differentiation therefore has many applications. In this study, we performed a novel functional screen of an epigenetic compound library to identify compounds that can modulate generation of TGF-β1 induced T regulatory cells. A screening strategy based on IFN-γ ELISA was designed to screen epigenetic compound library. Effect of hit compounds on Treg phenotype and function was assessed by RT-PCR, flow cytometry and suppression assays. TGF-β signalling proteins were assayed by western blotting. Chromatin Immunoprecipitation (ChIP) assay was used to assess epigenetic modifications at Foxp3 gene locus. We screened 160 compounds to identify hits capable of reversing TGF-β induced inhibition of IFN-γ production in activated spleen cells and CD4+ T cells. Two compounds EPZ004777 and FG-2216 consistently reversed TGF-β1 iTregs in terms of (a) differentiation of naive T cells into CD4+CD25+Foxp3+Treg cells, (b) Foxp3 target gene expression and (c) Treg suppressive function without affecting TGF-β downstream signalling. ChIP assay revealed that the compounds were able to reverse – TGF- β mediated decrease in epigenetic marks H3K27me3 and 5-mC and an increase in epigenetic marks H3K4me3 and H3K27Ac in the promoter and conserved non coding sequence (CNS1) regions of the Foxp3 gene. EPZ004777 and FG-2216 have been identified as potent epigenetic modulators that can reverse TGF-β1 induced T regulatory cells and may be used to treat diverse immune disorders.
Life Sciences published new progress about 1338466-77-5. 1338466-77-5 belongs to tetrahydrofurans, auxiliary class Epigenetics,Histone Methyltransferase, name is 1-(3-((((2R,3S,4R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea, and the molecular formula is C28H41N7O4, Computed Properties of 1338466-77-5.
Referemce:
https://en.wikipedia.org/wiki/Tetrahydrofuran,
Tetrahydrofuran | (CH2)3CH2O – PubChem