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ACY-775
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
ACY-775图片
CAS NO:1375466-18-4
规格:≥98%
包装与价格:
包装价格(元)
5mg询价
10mg询价
25mg询价
50mg询价
100mg询价
250mg询价
500mg询价

理化性质和储存条件
Molecular Weight (MW) 330.36
Formula C17H19FN4O2
CAS No. 1375466-18-4
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 100 mg/mL
Water: N/A
Ethanol: N/A
Chemical Name 2-((1-(3-Fluorophenyl)cyclohexyl)amino)-N-hydroxypyrimidine-5-carboxamide
Synonyms ACY-775; ACY 775; ACY775
实验参考方法
In Vitro

In vitro activity: ACY-775, a novel pyrimidine hydroxyl amide small molecule, is a brain bioavailable, highly potent and isoform-selective inhibitor of HDAC6 with IC50 of 7.5 nM. ACY-738 and ACY-775 inhibit HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs. In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity, but more limited brain bioavailability, ACY-738 and ACY-775 induce dramatic increases in α-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments. Interestingly, despite a lack of detectable effect on histone acetylation, ACY-738 and ACY-775 share the antidepressant-like properties of other HDAC inhibitors, such as SAHA and MS-275, in the tail suspension test and social defeat paradigm. These effects of ACY-738 and ACY-775 are directly attributable to the inhibition of HDAC6 expressed centrally, as they are fully abrogated in mice with a neural-specific loss of function of HDAC6. Furthermore, administered in combination, a behaviorally inactive dose of ACY-738 markedly potentiates the anti-immobility activity of a subactive dose of the selective serotonin reuptake inhibitor citalopram. These results validate new isoform-selective probes for in vivo pharmacological studies of HDAC6 in the CNS and reinforce the viability of this HDAC isoform as a potential target for antidepressant development.


Kinase Assay: ACY-775, a novel pyrimidine hydroxyl amide small molecule, is a brain bioavailable, highly potent and isoform-selective inhibitor of HDAC6 with IC50 of 7.5 nM. ACY-738 and ACY-775 inhibit HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs. In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity, but more limited brain bioavailability, ACY-738 and ACY-775 induce dramatic increases in α-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments.


Cell Assay: ndifferentiated RN46A-B14 cells, a line of immortalized rat raphe neuronal precursors, are grown. They are treated with 2.5 μM ACY-738, ACY-775, tubastatin A, 0.6 μM TSA or vehicle (0.1% DMSO) for 4 h. Samples are processed using histone extraction kit and quantified using protein assay.

In VivoBiodistribution 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. Mice are tested for immobility in the TST. At 30 min or 2 h after i.p. injection of ACY-738 (5, 50 mg/kg), ACY-775 (5, 50 mg/kg), and citalopram (0.5, 2, 20 mg/kg), a combination of the previous, or vehicle, mice are attached to the test rig and time immobile over 6 min is recorded. For open-field activity mice are injected with ACY-738 or ACY-775 at 5, 10, or 50 mg/kg or vehicle and allowed to explore. Activity is recorded
Animal model Mice
Formulation & Dosage 5, 50 mg/kg; i.p.
References Neuropsychopharmacology. 2014 Jan;39(2):389-400; Neurotherapeutics. 2017 Apr;14(2):417-428.
 
 
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