Thrilled to share our story on the first rationally designed #covalent #HDAC inhibitor! YSR734 uses an SNAr-reactive electrophile to engage a noncatalytic nitrosylation site cysteine in #HDAC2, showing in vitro activity in AML & #DuchenneMuscularDystrophy!
https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01236

The November Issue of @CellChemBiol is Online! Read it at: https://www.cell.com/cell-chemical-biology/current?utm_source=dlvr.it&utm_medium=mastodon #chemicalbiology #GPCR #RAF #STING #SARSCOV2 #ASO #PDL1 #HDAC #indoxylsulfate #E3ligase #UPS10 #targetID #luciferin #forwardgenetics

"In this work, we explored possibility of using drug-sensitivity data together with basal gene expression data on pancreatic cell lines to predict the combinatorial options available for HDACi and developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC. "

#Preprint #PDAC #HDAC

https://www.biorxiv.org/content/10.1101/2022.10.10.511584v3

Our recent work has focused on the development of small-molecule inhibitors for #HDAC enzymes as well as the "undruggable" transcription factors #STAT3 and #STAT5 as potential treatments for hematological malignancies and other cancers.
https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.0c01922
https://www.nature.com/articles/s41467-019-10422-7
https://www.nature.com/articles/s41375-017-0005-9