Benzoic acid, 4-[[[[5-[(phenylamino)methyl]-2-thiazolyl]carbonyl]amino]methyl]-, 2-propylhydrazide

HDAC3-IN-4 is a selective and orally active HDAC3 inhibitor with an IC50 of 89 nM. HDAC3-IN-4 induces the degradation of PD-L1 by regulating cathepsin B (CTSB) in the lysosomes, with a DC50 of 5.7 μM. HDAC3-IN-4 shows better selectivity for HDAC3 over HDAC1, HDAC6, HDAC7, and HDAC8[1].

HDAC3: 89 nM (IC₅₀); HDAC1: 730 nM (IC₅₀); HDAC6: >10 μM (IC₅₀); HDAC7: >10 μM (IC₅₀); HDAC8: >10 μM (IC₅₀)

[1] Zhiqiang Sun, et al. Discovery of Novel HDAC3 Inhibitors with PD-L1 Downregulating/Degrading and Antitumor Immune Effects. J Med Chem. 2024 Jul 20. DOI:10.1021/acs.jmedchem.4c01062