UM-002 is a highly potent, selective, brain penetrant BRD4 bromodomain inhibitor with IC50 of 8.8 and 2.4 nM for BRD4-1 and BRD4-2, respectively.
UM-002 is more potent than JQ1 at inhibiting BRD2-1, BRD4-1, and BRD4-2.
UM-002 reduces GBM cell proliferation more than JQ1, or the brain penetrant BET inhibitor MK-8628.
UM-002 not affect the enzymatic activity of histone deacetylases, histone acetyltransferases.
UM-002 inhibits GBM cell proliferation in vitro with EC50 of 0.13 and 0.24 uM for GBM22 cells and GBM39 cells, repectively.
UM-002 reduces proliferation of GBM cells co-cultured with cerebral brain organoids, reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors.
