AES-350 is a potent and orally active HDAC6 inhibitor (IC50 and Ki of 0.0244 μM and 0.035 μM, respectively), also exhibiting activity against HDAC-3, -8, and -11 in an enzymatic assay with IC50 values of 0.187 μM, 0.245 μM, and >1 μM, respectively. AES-350 triggers apoptosis in AML cells through HDAC inhibition and can be used for acute myeloid leukemia (AML) research.

HDAC3:187 nM, HDAC11:245 nM , HDAC6:24.4 nM

AES-350 (0.25-4 μM;?18 hours) induces MV4-11 cells apoptosis in a dose-dependent manner.?The late apoptosis ratios are 8.74%, 11.7%,16.08%, 30.97%, and 38.48%, respectively at 0.25 μM-4 μM.?AES-350 has submicromolar activity (IC50=0.58±0.13 μM) against MV4-11 cells than to that of vorinostat (IC50=0.31±0.061 μM).?AES-350 is more ligand efficient and exemplifies a large therapeutic index (IC50>30 μM in noncancerous MRC-9 cells).?AES-350 is also shown to be effective in AML-3 (acute myeloid leukemia) cells (IC50=0.73 ± 0.12 μM).?An ELISA is performed using HeLa cervical cancer cell lysates, and HeLa cells highly express HDAC6 and are sensitive to AES-350.?Correspondingly, ELISA assays depicted a dose-dependent increase in HDAC6 inhibition (IC50=0.58±0.13 μM), Western blot analysis shows that AES-350 (0.1-10 μM) induces a dose-dependent increase in acetylated α-tubulin (Ac-α-tubulin), a substrate of HDAC.