Merck60

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Merck60（BRD 6929，Compound-60）是一种有效的、选择性的、脑渗透性的 HDAC1 和 HDAC2 抑制剂，IC50 分别为 1 nM 和 8 nM。

Merck60 (BRD 6929, Compound-60)?is a potent, selective and brain-penetrant inhibitor of HDAC1 and HDAC2 with IC50 of 1 nM and 8 nM respectively; displays 50-400 fold selectivity over class I HDAC3 (IC50?=?458 nM) and no appreciable inhibition of HDAC8 or of the class II HDACs (IC50>30 uM); alters gene expression in brain circuits involved in mood regulation, improves mood-related behaviors in mice.

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.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 <0.2 nM, 1.5nM, and 270 nM for HDAC 1, 2 and 3, respectively. The T1/2 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 EC50 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 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.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.

BRD 6929 | Compound-60

Cell Cycle/DNA Damage

HDAC

HDAC

——

——

849234-64-6

351.424

C19H17N3O2S

>98% (HPLC)

In Vitro:?DMSO : 5 mg/mL (14.23 mM助)

——

4-acetamido-N-(2-amino-5-(thiophen-2-yl)phenyl)benzamide

(-20℃)

With Ice Pack

≥ 2 years