AES-350 is a potent and orally active HDAC6 inhibitor with an IC 50 and a K i of 0.0244 μM and 0.035 μM, respectively. AES-350 is also against HDAC3 , HDAC8 in an enzymatic activity assay with IC 50 values of 0.187 μM and 0.245 μM, respectively. AES-350 triggers apoptosis in AML cells through HDAC inhibition and can be used for acute myeloid leukemia (AML) research
In Vitro
In contrast, AES-350 has submicromolar activity (IC 50 =0.58±0.13 μM) against MV4-11 cells than to that of vorinostat (IC 50 =0.31±0.061 μM). AES-350 is more ligand efficient and exemplifies a large therapeutic index (IC 50 >30 μM in noncancerous MRC-9 cells). AES-350 is also shown to be effective in AML-3 (acute myeloid leukemia) cells (IC 50 =0.73 ± 0.12 μM). 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. 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 (IC 50 =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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Apoptosis AnalysisCell Line: MV4-11 cells Concentration: 0.25 μM; 0.5 μM; 1.00 μM; 2.00 μM; 4.00 μM Incubation Time: 18 hours Result: Revealed a clear dosedependent increase in the percentage of cells entering late-stage apoptosis, similar to SAHA.
In Vivo
AES-350 (oral gavage; 20 mg/kg; single dose) exhibits a relative good pharmacokinetic (PK) properties in CD-1 mice. The single dose oral bioavailability (F%) of 51 is 19.8%. In comparison, the reported F% for SAHA in mice is significantly lower (8%) . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:HDAC6 24.4 nM (IC 50 ) HDAC3 187 nM (IC 50 ) HDAC11 245 nM (IC 50 )
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