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In vitro IC ₅₀ for HDAC1-9 by BRD-6929 using recombinant human HDAC enzymes and HDAC class-specific substrates. BRD-6929 and substrate are incubated for 180 min (HDAC1-3) to control for HDAC1-3 inhibition, BRD-6929 is against HDAC1, HDAC2, HDAC3 and HDAC4-9 with IC ₅₀ s of 0.001 µM, 0.008 µM, 0.458 µM and >30 µM, respectively. In vitro binding affinity (K _i ) and kinetics (half-life ‘T _1/2 ′ in minutes) for HDAC 1, 2 and 3 incubated with BRD-6929 (10 µM), the K _i values are <0.2 nM, 1.5nM, and 270 nM for HDAC 1, 2 and 3, respectively. The T _1/2 values are >2400 mins, >4800 mins, and 1200 mins for HDAC 1, 2 and 3, respectively. BRD-6929 (1 and 10 uM) does not cause an increase or decrease in overall cell number in brain region specific primary cultures. Additionally, BRD-6929 (10 uM) causes an increase in H4K12 acetylation in brain region specific primary cultures (striatum).BRD-6929 (1-10 uM; 6 hours) causes a significant increase in H2B acetylation in primary neuronal cell cultures. BRD-6929 (1-20 uM; 24 hours) induces a dose-dependent acetylation of H4K12ac with an EC ₅₀ of 7.2 µM in cultured neurons.BRD-6929 potentiates the efficacy of gnidimacrin (a PKC Agonist) against latent HIV-1.

BRD-6929 (intraperitoneal injection; 45 mg/kg; single dose) exhibits a C _max , T _1/2 and AUC values of 17.7 μM, 7.2 hours, and 25.6 μM/L*hr, respectively in plasma. It shows a C _max , T _1/2 and AUC values of 0.83 μM, 6.4 hours, and 3.9 μM/L*hr, respectively in brain.BRD-6929 (intraperitoneal injection; 45 mg/kg; 10 days) acts as a deacetylase inhibitor in mouse brain. It significantly increases acetylation in each brain region by 1.5- to 2.0-fold compared to vehicle. The western blotting reveals that BRD-6929 significantly increases acetylation of histone H2B (tetra-acetylated), H3K9 and H4K12 in cortex, ventral striatum and hippocampus after the 10th daily treatment in adult male C57BL/6J mice.