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ACY-775

CAS No. : 1375466-18-4

MCE 站：ACY-775

产品活性：ACY-775 是一个有效的，选择性强的组蛋白脱乙酰酶 6 (HDAC6) 抑制剂 IC₅₀ 值为 7.5 ?nM。

研究领域：Cell Cycle/DNA Damage  |  Epigenetics

作用靶点：HDAC

In Vitro: In vehicle-treated cells, α-tubulin is mainly presented in the deacetylated form, while histone 3 is clearly acetylated. Upon treatment with ACY-775, a clear enhancement of the acetylation of α-tubulin is visible, while histone acetylation remains unaltered. Acetylation of α-tubulin is visualized by immunofluorescence and the intensity in the neurites of the neurons is quantified and normalized to the length of the fluorescent signal. In vehicle-treated DRG neurons, acetylated α-tubulin is already present. Upon treatment with ACY-775 the signal intensity of acetylated α-tubulin increases significantly. Significant increase in motility of mitochondria and also the total number of mitochondria within the neurites are observed compare with vehicle-treated DRG neurons. A significantly higher number of retrogradely transport mitochondria is observed in DRG neurons treated with ACY-775 compare with vehicle-treated cells.

In Vivo: Biodistribution profiles of ACY-738, ACY-775, and tubastatin A are examined after acute dosing at 5 or 50?mg/kg over 2?h. At t=30?min after acute 50?mg/kg injection, respective plasma levels of ACY-738 and ACY-775 are 515?ng/mL (1.9?μM) and 1359?ng/mL (4.1?μM). Elimination from plasma is rapid, with plasmatic half-life of 12?min and concentration below 10?ng/mL after 2?h. Nevertheless, areas under concentration time curves for brain and plasm calculated over 2?h for both ACY-738 and ACY-775 lead to ratios >1. When ACY-738 (5?mg/kg) or ACY-775 (50?mg/kg) are administered repeatedly in wild-type mice at 24?h, 4?h, and 30?min before killing, significant increases in α-tubulin acetylation are observed in all tested brain regions.

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