L002 is an inhibitor of p300 histone acetyltransferase (KAT3B; IC50 = 1.98 μM in vitro). It has weaker inhibitory effects against PCAF and GCN5 (IC50s = 35 and 34 μM, respectively) and is specific for p300 over a panel of additional acetyltransferases, deacetylases, and methyltransferases. L002 blocks acetylation of histones and p53 in cells treated with trichostatin A or etoposide, respectively, and reduces STAT3 phosphorylation, which requires p300-mediated acetylation of STAT3. It induces growth arrest and apoptosis in certain cancer cell lines and, when administered intraperitoneally in mice, suppresses the growth of triple-negative breast cancer xenografts.
