HDAC3-IN-2 (compound 4i) is a pyrazinyl hydrazide-based HDAC3 inhibitor ( IC 50 : 14 nM) that efficiently targets triple-negative breast cancer cells. HDAC3-IN-2 is cytotoxic with an IC 50 of 0.55 μM against 4T1 and an IC 50 of 0.74 μM against MDA-MB-231. HDAC3-IN-2 has anti-tumor efficacy in vivo in tumor-bearing mouse models, selectively increasing the acetylation levels of H3K9, H3K27 and H4K12, increasing the contents of apoptosis-related caspase-3 , caspase-7 and cytochrome c, and reducing Proliferation-related Bcl-2 , CD44 , EGFR , and Ki-67 levels.
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