HDAC8-IN-3 (compound P19) is a highly potent HDAC8 inhibitor with an IC50 value of 9.3 μM, inducing thermal stabilization, cytotoxicity, and apoptosis specifically in leukemic cell lines [1].

HDAC1:＞50 μM, HDAC5:＞50 μM, HDAC2:41 μM, HDAC8:9.3 μM, HDAC8:＞50 μM, HDAC3:＞50 μM, HDAC4:＞50 μM, HDAC6:17 μM

HDAC8-IN-3 (compound P19), at concentrations ranging from 5-200 μM over 48 hours, exhibits cytotoxic effects in leukemic cell lines, with specific activity demonstrated in HEK293T cells. When administered at 50 μM, this compound notably inhibits glucose transporter 1 (GLUT1)-mediated glucose transport by reducing GLUT1 expression, achieving a half-maximal inhibitory concentration (IC 50) of 28.2 μM. Additionally, at a concentration of 79.9 μM over 24 hours, HDAC8-IN-3 can induce apoptotic death in CEM leukemia cells, as evidenced by a significant increase in the percentage of apoptotic cells to 60.97%. Cytotoxicity assays conducted with a fixed concentration of 50 μM for 48 hours on K562, KCL22, and CEM leukemia cell lines reported IC 50 values of 79.9, 85.4, and 43.2 μM, respectively, thereby confirming the compound’s effectiveness in inhibiting cell viability across various leukemia models.