Histone Acetyltransferase Inhibitor VIII; NU9056

Biochem/physiol Actions

Reversible: yes

Primary TargetKAT5

Cell permeable: yes

General description

A cell-permeable disulfane compound that is reported to be more potent against KAT5/Tip60 than PCAF, p300, and GCN5 in cell-free HAT activity assays (IC₅₀ ≤2, ≤36, ≤60, and >100 µM, respectively) and effectively reduce H3K14, H4K8, H4K16, but not α-tubulin, acetylation level in LNCaP prostate cancer cells (max inhibition at 5-10 µM). Shown to induce cell cycle arrest and apoptosis (17 to 24 µM) in LNCaP cultures and exhibit antiproliferation activity in both androgen-responsive and androgen-independent CaP cultures (GI₅₀ from 7.5 to 27 µM).Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

A cell-permeable disulfane compound that is reported to be more potent against KAT5/Tip60 than PCAF, p300, and GCN5 in cell-free HAT activity assays (IC₅₀ ≤2, ≤36, ≤60, and >100 µM, respectively) and effectively reduce H3K14, H4K8, H4K16, but not α-tubulin, acetylation level in LNCaP prostate cancer cells (max inhibition at 5-10 µM; 2 µM TSA, Cat. No. 647925, added in the last 4 h of 6 h NU9056 treatment to block HDAC activity). Shown to induce cell cycle arrest (% subG1 population after 24 h/48 h/72 h/ 96 h/dose = 9.3%/15%/22%/61%/17 µM and 12%/23%/25%/92%/24 µM) and apoptosis (fold caspase-9 cleavage increase/dose in 24 h = 2.5/17 µM & 3.5/24 µM; fold caspase-3 cleavage increase/dose in 96 h = 6.3/17 µM & 11/24 µM) in LNCaP cultures and exhibit antiproliferation activity in both androgen-responsive and androgen-independent CaP cultures (GI₅₀ in three doubling time = 7.5, 12, 16, 24, and 27 µM, respectively, against WR22rvl, LNCaP-CdxR, LNCaP-AI, LNCaP, and PC3 cells).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Coffey, K., et al. 2012. PLoS One.7, e45539.

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Standard Handling (A)