| Bioactivity | 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 Ki of 0.2 and 1.5 nM, respectively. BRD-6929 can be used for mood-related behavioral model research[3]. | |||||||||
| Invitro | 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 (Ki) and kinetics (half-life ‘T1/2′ in minutes) for HDAC 1, 2 and 3 incubated with BRD-6929 (10 µM), the Ki 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 Cmax, T1/2 and AUC values of 17.7 μM, 7.2 hours, and 25.6 μM/L*hr, respectively in plasma. It shows a Cmax, T1/2 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]. | |||||||||
| Name | BRD-6929 | |||||||||
| CAS | 849234-64-6 | |||||||||
| Formula | C19H17N3O2S | |||||||||
| Molar Mass | 351.42 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [1]. Li-Huei Tsai, et al. Inhibition of hdac2 to promote memory. patent/US20120101147 [2]. Schroeder FA, et al. A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and altersmouse behavior in two mood-related tests. PLoS One. 2013 Aug 14;8(8):e71323. [3]. Huang L, et al. Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor. ACS Med Chem Lett. 2018 Feb 6;9(3):268-273. |