HDAC3-IN-4 is a selective and orally active HDAC3 inhibitor with an IC 50 of 89 nM. HDAC3-IN-4 induces the degradation of PD-L1 by regulating cathepsin B (CTSB) in the lysosomes, with a DC 50 of 5.7 μM. HDAC3-IN-4 shows better selectivity for HDAC3 over HDAC1 , HDAC6 , HDAC7 , and HDAC8.