An HDAC6 inhibitor
ACY-775 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 0.0075 ?M).1 It is selective for HDAC6 over HDAC1, HDAC2, and HDAC3 (IC50s = 2.1, 2.5, and 11.2 ?M, respectively). ACY-775 (2.5 ?M) increases α-tubulin acetylation at lysine 40 in RN46A-B14 serotonergic cells. It increases the distance traveled in the center of the open field test and decreases immobility time in the tail suspension test, indicating anxiolytic- and antidepressant-like activities, respectively, in mice when administered at a dose of 50 mg/kg.
1.Jochems, J., Boulden, J., Lee, B.G., et al.Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailabilityNeuropsychopharmacology39(2)389-400(2014)
Cell experiment: | Undifferentiated 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. |
Animal experiment: | 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[2]. |
参考文献: [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. | |
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