L002, a potent, cell-permeable, reversible, and specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 μM, directly binds the acetyl-CoA pocket and competitively inhibits the FATp300 catalytic domain. By blocking histone acetylation, p53 acetylation, and STAT3 activation, L002 shows potential in the treatment of hypertension‐induced cardiac hypertrophy and fibrogenesis.

GCN5:34 µM , PCAF:35 µM , KAT3B:1.98 uM

L002 also has weak inhibitory effects against PCAF and GCN5 (IC50s =35 and 34 μM, respectively) and is specific for p300 over a panel of deacetylases, additional acetyltransferases, and methyltransferases.

L002 reverses hypertension‐induced cardiac hypertrophy and fibrosis by treatment of mice after inducing hypertension for two weeks significantly.It also reduces the levels of perivascular and interstitial collagen in the myocardium compared to non-treated hypertensive mice.