HDAC6-IN-42 (compound 2b) is an HDAC6 inhibitor with an IC50 of 0.009 μM, demonstrating significant anti-leukemia activity and synergistic effects with Decitabine, indicating its potential use in the research of Acute Myeloid Leukemia (AML).

HDAC6:0.009 μM

HDAC6-IN-42 exhibits anti-proliferative activity that is more than five times greater than HPOB against three leukemia cell lines (HAL01: 2.32±0.77 μM, HL60: 2.04±0.62 μM, Jurkat: 3.08±0.59 μM). It shows higher selectivity for HDAC6 (IC50 = 0.787 μM; SIHDAC2/6=87) and HDAC3 (IC50 = 0.520 μM; SIHDAC3/6=58) compared to HDAC1 (IC50 = 0.228 μM; SIHDAC1/6=25). At a concentration of 1.5 μM for 48 hours, HDAC6-IN-42 displays no cytotoxicity to healthy fibroblasts and significantly increases the percentage of late apoptotic cells. Additionally, HDAC6-IN-42 demonstrates outstanding performance in inducing a synergistic effect with the drug Decitabine against AML cells.