BRD-6929

BRD-6929 is a potent, selective brain-penetrant inhibitor of class I histone deacetylase HDAC1 and HDAC2 inhibitor with IC₅₀ of 1 nM and 8 nM, respectively. BRD-6929 shows high-affinity to HDAC1 and HDAC2 with K_i of 0.2 and 1.5 nM, respectively. BRD-6929 can be used for mood-related behavioral model research^[3]. In Vitro: In vitro IC₅₀ 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 IC₅₀s of 0.001 μM, 0.008 μM, 0.458 μM and >30 μM, respectively^[1].
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^[1].
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)^[1].
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 EC₅₀ of 7.2 μM in cultured neurons^[1].
BRD-6929 potentiates the efficacy of gnidimacrin (a PKC Agonist) against latent HIV-1^[3].
In Vivo: 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^[1].
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^[1].