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A HAT inhibitor for KAT (KAT6A)

The lysine acetyltransferase KAT6A and its paralog KAT6B belong to the MYST family of KATs and act by acetylation of histone and nonhistone proteins. They regulate diverse biological processes and play essential roles in cell cycle progression, stem cell development and diverse cancers such as acute myeloid leukaemia, lung and breast cancers. ​

The chemical probe WM-1119 represents a novel class of inhibitors for the KAT family.  It strongly binds to KAT6A (KD 2 nM) and is competitive with acetyl-CoA. WM-1119 is effective in preventing the progression of lymphoma in mice by substantially reducing the proportion and overall number of tumor cells. ​

This class of inhibitors will help to accelerate the development of therapeutics that target gene transcription regulated by histone acetylation. ​

WM-1119 binding site WM-1119 spleen size

Left: Binding mode of WM-1119 in KAT6A (PDB 6CT2).​

Right: Spleen size in mice drastically reduced after WM-1119 treatment 4x per day for 14 days as compared to vehicle (left). ​

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For more information about the WM-1119 chemical probe visit the Chemical Probes Portal:  logo

WM-1119 chemical probe  Control compound

 

Chemical probe WM-1119                         Negative control of WM-1119: WM-2474