HDAC3-IN-2 (compound 4i), a pyrazinyl hydrazide-based HDAC3 inhibitor with an IC50 of 14 nM, effectively targets triple-negative breast cancer cells. Demonstrating cytotoxic activity, HDAC3-IN-2 exhibits an IC50 of 0.55 μM against 4T1 cells and 0.74 μM against MDA-MB-231 cells. In vivo, it shows anti-tumor efficacy in tumor-bearing mouse models by selectively elevating acetylation of histones H3K9, H3K27, and H4K12, enhancing apoptosis-inducing proteins caspase-3, caspase-7, and cytochrome c, and diminishing proliferation markers Bcl-2, CD44, EGFR, and Ki-67 [1].