| Identification | Back Directory | [Name]
2-(1-Phenyl-cyclopropylamino)-pyrimidine-5-carboxylic acid hydroxyamide | [CAS]
1375465-91-0 | [Synonyms]
ACY-738
CS-2244
ACY 738; ACY738
ACY738;ACY-738;ACY 738
2-(1-phenylcyclopropylamino)-N-hydroxypyrimidine-5-carboxamide
N-Hydroxy-2-[(1-phenylcyclopropyl)amino]-5-pyrimidinecarboxamide
5-Pyrimidinecarboxamide, N-hydroxy-2-[(1-phenylcyclopropyl)amino]-
2-(1-Phenyl-cyclopropylamino)-pyrimidine-5-carboxylic acid hydroxyamide | [Molecular Formula]
C14H14N4O2 | [MDL Number]
MFCD28347706 | [MOL File]
1375465-91-0.mol | [Molecular Weight]
270.29 |
| Chemical Properties | Back Directory | [density ]
1.433±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:32.0(Max Conc. mg/mL);118.39(Max Conc. mM) | [form ]
A crystalline solid | [pka]
7.75±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
ACY-738 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 1.7 nM).1 It is selective for HDAC6 over HDAC1-3 (IC50s = 94, 128, and 218 nM, respectively). ACY-738 (5 mg/kg) increases acetylation of α-tubulin in mouse brain. It increases exploratory activity in a novel open-field test and reduces immobility time in a tail suspension test in wild-type, but not neural cell-selective HDAC6 knockout, mice when administered at a dose of 50 mg/kg, indicating anxiolytic and antidepressant-like activity, respectively. ACY-738 (100 mg/kg in the diet) attenuates decreases in caudal nerve sensory nerve action potential (SNAP) amplitude and increases in hind paw mechanical hypersensitivity in a mouse model of peripheral neuropathy induced by vincristine (Item No. 11764).2 It decreases hepatorenal cystogenesis in a rat model of polycystic liver disease when administered at a dose of 30 mg/kg.3 | [Uses]
ACY-738 is a potent, selective and orally-bioavailable HDAC6 inhibitor, with an IC50 of 1.7 nM; ACY-738 also inhibits HDAC1, HDAC2, and HDAC3, with IC50s of 94, 128, and 218 nM. | [in vivo]
ACY-738 (5?mg/kg) leads to significant increase in α-tubulin acetylation in whole-brain lysates. ACY-738 (50?mg/kg) fails to produce an enhancement of locomotor activity in WT mice tested in a home cage environment[1]. ACY-738 (5 mg/kg) reaches a maximum plasma concentration of 1310 ng/mL at 0.0830 h following treatment. ACY-738 (5 mg/kg BW) alters BM B cell differentiation, but shows no significant effect on IgG and C3 deposition in NZB/W mice. ACY-738 (20 mg/kg) significantly attenuates the severity of proteinuria in NZB/W F1 mice. ACY-738 (5 mg/kg) shows a significant decrease in anti-dsDNA production in NZB/W mice as they aged. ACY-738 (5, 20 mg/kg) attenuates sera IL-1β production as the NZB/W mice aged. ACY-738 (5 mg/kg) significantly reduces glomerular IL-6 and IL-10 mRNA levels by more than 50% while treatment with 20 mg/kg ACY-738 reduced IL-6 and IL-10 mRNA to non-detectable levels[2]. | [IC 50]
HDAC6: 1.7 nM (IC50); HDAC1: 94 nM (IC50); HDAC2: 128 nM (IC50); HDAC3: 218 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Jochems J, et al. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400. DOI:10.1038/npp.2013.207
[2] Regna NL, et al. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73. DOI:10.1016/j.clim.2015.11.007
[3] Mithraprabhu S, et al. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013 Aug;162(4):559-62. DOI:10.1111/bjh.12388 |
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