SGF29 inhibitor DC60 is a small molecule inhibitor of Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 (SGF29, CCDC101) with IC50 of 6.4 uM, binds to SGF29 second Tudor domain (SGF29 Tudor 2) and blocks SGF29 chromatin binding domain.
DC60 inhibits interaction of SGF29 Tudor 2 with its natural ligand H3K4me3 peptide with IC50 of 6.4 uM in AlphaScreen assays.
DC60 shows broad spectrum anticancer activity against of hematopoietic cancer cells (MLL-r leukemia cells, IC50=5.7-16.0 uM), solid tumor cells are substantially less sensitive.
DC60 also reduces the SGF29 protein level in leukemic cells, as well as the level of KAT2A and KAT2B protein.
DC60 suppresses leukemia progression in mice receiving MLL-AF9 leukemia.
DC60 also suppresses the expression of RPL8 and RPS2, resembling the impact caused by SGF29 depletion in leukemia.
SGF29 is a component of SAGA/ATAC acetyltransferase complexes, as a crucial factor for H3K9 acetylation, ribosomal gene expression, and leukemogenesis.