ACY738 对重组 HDAC6 具有抑制活性IC50值为 1.7 nM。它也可抑制 HDAC1、HDAC2 和 HDAC3 的活性，IC50值分别为 94、128 和 218 nM。

ACY-738 demonstrates inhibitory activity against recombinant HDAC6 (IC50: 1.7 nM), with respective average selectivity over class I HDACs being 100-fold.

ACY-738 increases the acetylated (lysine 40) fraction of α-tubulin in RN46A-B14 cells at the concentration of 2.5?μM. The effect that ACY-738 (10 μM) induces cell death is similar to LBH589 and FK228.

ACY-738 (5?mg/kg) leads to obviously increase in α-tubulin acetylation in whole-brain lysates. ACY-738 (50?mg/kg) cannot produce an enhancement of locomotor activity in WT mice tested in a home cage environment. 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 (5 mg/kg) reaches a maximum plasma concentration of 1310 ng/mL at 0.0830 h following treatment. 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. It also 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. ACY-738 (5, 20 mg/kg) attenuates sera IL-1β production as the NZB/W mice aged.

Recombinant kinase domain of EGFR L858R and T790M-L858R mutants are incubated with EGF816 to confirm covalent modification of EGFR and site of adduction. Recombinant enzyme is incubated at room temperature with a 20-fold molar excess of compound in 40 mM Tris, pH 8, 500 mM NaCl, 1% glycerol, 5 mM TCEP for 1 h. The reaction is quenched by addition of dithiothreitol (DTT, 80-fold excess to compound) and transfer to ice. A third of the reaction (10 μL) is processed for intact MS by adding an equal volume of 6 M Guan HCl, 100 mM Tris, pH 8, 20 mM DTT, 10 mM TCEP and incubating at room temperature for 15 min. Intact MS analysis is performed on an Agilent 6520 QToF mass spectrometer equipped with a dual spray ion source (IS of 4500 V, fragmentor of 250 V, fas temp of 350°C, and skimmer of 75 V). The samples are injected onto a PLRP-S column (2.1 mm × 50 mm), heated to 60°C, and desalted for 2 min at 500 μL/min and 3% B prior to elution with a fast gradient of 3-50% B in 3 min (B, 0.1% formic acid). The data are analyzed in MassHunter for automatic peak selection, integration, and spectral deconvolution with a mass range of 15?000-75?000 Da.

1375465-91-0

C14H14N4O2

270.292

ACY 738

DMSO:32 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years