ACY-775 - HDAC 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEACY-775Cat. No.: HY-19328CAS No.: 1375466-18-4分式: CHFNO分量: 330.36作靶點: HDAC作通路: Cell Cycle/DNA Damage; Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (302.70 mM; Need u

2、ltrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.0270 mL 15.1350 mL 30.2700 mL5 mM 0.6054 mL 3.0270 mL 6.0540 mL10 mM 0.3027 mL 1.5135 mL 3.0270 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 ACY-775個有效的，選擇性強的組蛋脫酰酶 6 (HDAC6) 抑制劑 IC50 值為 7.5 nM。IC50 & T

3、arget HDAC6 HDAC1 HDAC2 HDAC37.5 nM (IC50) 2123 nM (IC50) 2570 nM (IC50) 11223 nM (IC50)體外研究In vehicle-treated cells, -tubulin is mainly presented in the deacetylated form, while histone 3 is clearlyacetylated. Upon treatment with ACY-775, a clear enhancement of the acetylation of -tubulin is visibl

4、e, while1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEhistone acetylation remains unaltered. Acetylation of -tubulin is visualized by immunofluorescence and theintensity in the neurites of the neurons is quantified and normalized to the length of the fluorescent signal. Invehicle-treated DRG neur

5、ons, acetylated -tubulin is already present. Upon treatment with ACY-775 thesignal intensity of acetylated -tubulin increases significantly. Significant increase in motility of mitochondriaand also the total number of mitochondria within the neurites are observed compare with vehicle-treatedDRG neur

6、ons. A significantly higher number of retrogradely transport mitochondria is observed in DRGneurons treated with ACY-775 compare with vehicle-treated cells 1.體內(nèi)研究 Biodistribution profiles of ACY-738, ACY-775, and tubastatin A are examined after acute dosing at 5 or 50mg/kg over 2h. At t=30min after

7、acute 50mg/kg injection, respective plasma levels of ACY-738 and ACY-775 are 515ng/mL (1.9M) and 1359ng/mL (4.1M). Elimination from plasma is rapid, with plasmatic half-life of 12min and concentration below 10ng/mL after 2h. Nevertheless, areas under concentration timecurves for brain and plasm calc

8、ulated over 2h for both ACY-738 and ACY-775 lead to ratios 1. When ACY-738 (5mg/kg) or ACY-775 (50mg/kg) are administered repeatedly in wild-type mice at 24h, 4h, and 30minbefore killing, significant increases in -tubulin acetylation are observed in all tested brain regions 2.PROTOCOLCell Assay 2 Un

9、differentiated RN46A-B14 cells, a line of immortalized rat raphe neuronal precursors, are grown. They aretreated with 2.5M ACY-738, ACY-775, tubastatin A, 0.6M TSA or vehicle (0.1% DMSO) for 4h. Samplesare processed using histone extraction kit and quantified using protein assay.MCE has not independ

10、ently confirmed the accuracy of these methods. They are for reference only.Animal Mice are tested for immobility in the TST. At 30min or 2h after i.p. injection of ACY-738 (5, 50mg/kg), ACY-Administration 2 775 (5, 50mg/kg), and citalopram (0.5, 2, 20mg/kg), a combination of the previous, or vehicle

11、, mice areattached to the test rig and time immobile over 6min is recorded. For open-field activity mice are injected withACY-738 or ACY-775 at 5, 10, or 50mg/kg or vehicle and allowed to explore. Activity is recorded 2.MCE has not independently confirmed the accuracy of these methods. They are for

12、reference only.REFERENCES1. Veronick Benoy, et al. Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-ToothDisease. 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.McePdfHeightCautio