BRD6688

BRD6688 is a selective HDAC inhibitor with IC₅₀ values of 0.021 μM and 0.100 μM for HDAC1 and HDAC2, respectively. BRD6688 induces histone H4K12 and H3K9 acetylation. BRD6688 decreases CK2-induced HDAC2 phosphorylation. BRD6688 induces macrophage M1 to M2 polarization and renal cell proliferation. BRD6688 can be used for research on neurodegenerative diseases, acute kidney injury, pain, and anxiety disorders^{[1][2][3][4][5][6][7]}. In Vitro:BRD6688 (3-fold serial dilution starting from 33.33 μM; 60 min) is a potent inhibitor of human recombinant HDAC1 and HDAC2 with an IC₅₀ of 0.100 μM for HDAC2, demonstrating greater than 115-fold selectivity for HDAC1/2 over HDAC3^[1].
BRD6688 exhibits kinetically selective inhibition of HDAC2 with a residence time half-life of 381 min, compared to 65 min for HDAC1^[1].
BRD6688 (10 μM; 24 h) increases H4K12 and H3K9 histone acetylation in primary mouse forebrain neuronal cultures at 10 μM^[1].
BRD6688 (5-10 μM) suppresses LTA4H gene expression in HREpiC cells under H/R conditions^[2].
BRD6688 (5 μM) decreases LTB₄ secretion in HREpiC cells under H/R conditions^[2].
BRD6688 (5 μM) reduces the proportion of LTA4H-positive HREpiC cells^[2].
BRD6688 (5 μM) reduces p-HDAC levels in HREpiC cells^[2].
BRD6688 (5 μM) inhibits CK2 activity in HREpiC cells under hypoxia/reoxygenation^[2].
BRD6688 inhibits p-HDAC2 and LTA4H expression in HDAC2-overexpressing HREpiC cells^[2].
BRD6688 reduces LTB₄ production in HDAC2-overexpressing HREpiC cells^[2].
BRD6688 (5-10 μM; 48 h) reduces BLT1 expression but not BLT2 expression in RAW264.7 macrophages^[2].
BRD6688 (5 μM; 2 days) promotes M2 phenotype and suppresses M1 phenotype in RAW264.7 macrophages^[2].
Selective HDAC2 inhibition by BRD6688 and BRD4884 rescues memory deficits in impaired mice through increased H4K12 and H3K9 acetylation without affecting episodic memory^[3].
BRD6688 (4 μM; 24 h) acts as a high-ranking activator of Srrm4-dependent microexon splicing in N2A cells^[7].
BRD6688 (10 μM; 24 h) promotes microexon splicing inclusion with a relatively limited impact on global gene expression in N2A cells^[7].
BRD6688 (10 μM) promotes microexon splicing largely independently of effects on Srrm4 expression, and its effects are additive with RDR00572 in N2A cells^[7].
The HDAC 2 inhibitor BRD6688 (10-100 nM; 24 h) reduces the mRNA expression of IL-1β, TNF, MIP-1α, and MCP-1 in TNF-stimulated human PBMCs/monocytes in a dose-dependent manner^[6].
The HDAC 2 inhibitor BRD6688 (10-100 nM; 24 h) significantly reduces the protein secretions of IL-1β and MCP-1 from TNF-stimulated human PBMCs/monocytes, but does not affect secreted TNF, MIP-1α, RANTES, IFN-γ, or IL-10 levels^[6].
The HDAC 2 inhibitor BRD6688 (10-1000 nM; 10 days) significantly reduces the bone-resorbing activity of TNF-stimulated human osteoclasts at 1000 nM, but has minimal effect on osteoclast formation in the absence of TNF^[6].
BRD6688 (10 nM; 10 days) reduces the mRNA expression of osteoclast-related factors TRAF-6, TRAP, Cathepsin K, and DC-STAMP at day 14 in TNF-stimulated human osteoclasts, but does not affect MCP-1, MIP-1α, or RANTES expression^[6]. In Vivo:BRD6688 (1 mg/kg; i.p.; daily; 10 days) rescues memory deficits and increases H4K12 acetylation in hippocampal CA1 neurons in CK-p25 mice^[1].
BRD6688 (1 mg/kg; i.p.; daily; 10 days) significantly attenuates Paclitaxel (HY-B0015)-induced mechanical allodynia and partially reverses spinal glutamate accumulation in a rat model of chemotherapy-induced peripheral neuropathy^[4].
Pharmacological inhibition of Hdac2 by BRD6688 (1 mg/kg; i.p.; single dose; 6 h before extinction training) before extinction training reduces spontaneous fear memory recovery and decreases Acan/Aggrecan expression in wild-type mice, but this effect is occluded in PV+ cell-specific Hdac2 conditional knockout mice^[5].