| 產品描述： | ACY-775 is a potent and selective inhibitor of the of histone deacetylase 6 (HDAC6) with an IC50 of 7.5?nM. ACY775 also inhibits metallo-β-lactamase domain-containing protein?2 (MBLAC2) |
| 靶點： |
HDAC6:7.5 nM (IC50);HDAC1:2123 nM (IC50);HDAC2:2570 nM (IC50);HDAC3:11223 nM (IC50);HDAC |
| 體外研究： |
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 |
| 體內研究： |
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 |
| 參考文獻： |
1. Veronick Benoy, et al. Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-Tooth Disease. Neurotherapeutics. 2017 Apr; 14(2): 417-428. 2. Jeanine Jochems et al. Antidepressant-Like Properties of Novel HDAC6-Selective Inhibitors with Improved Brain Bioavailability. Neuropsychopharmacology. 2014 Jan; 39(2): 389-400. 3. Severin Lechner, et al. Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nat Chem Biol. 2022 Apr 28. |
| 溶解性： |
Soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
3.027 ml |
15.135 ml |
30.27 ml |
| 5 mM |
0.605 ml |
3.027 ml |
6.054 ml |
| 10 mM |
0.303 ml |
1.514 ml |
3.027 ml |
| 50 mM |
0.061 ml |
0.303 ml |
0.605 ml |
|
| 注意： |
部分產品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。 |
上海工商
危險品化學品經營許可證（不帶存儲）
營業執照(三證合一)
北京