AES-350

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AES-350 是一种有效的口服活性 HDAC6 抑制剂（IC50 和 Ki 分别为 0.0244 μM 和 0.035 μM）。

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

In contrast, 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).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 (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. Apoptosis Analysis Cell 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.

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%).

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Cell Cycle/DNA Damage

HDAC

HDAC11|HDAC3|HDAC6

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847249-57-4

312.36

C18H20N2O3

>98% (HPLC)

DMSO:100 mg/mL (320.14 mM; Need ultrasonic)

CC(C)(C)C1=CC=C(C(NC2=CC=C(C(NO)=O)C=C2)=O)C=C1

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(-20℃)

With Ice Pack

≥ 2 years