Description
Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). SIRT2 deacetylates histone H4 and α-tubulin and functions as a regulator of cell cycle progression, a determinant of myelination, a modulator of autophagy, and a suppressor of brain inflammation. SirReal2 is an aminothiazole that acts as a SIRT-rearranging ligand to selectively inhibit SIRT2 (IC
50 = 140 nM). SirReal2 is >1,000-fold more potent at inhibiting the activity of SIRT2 than that of SIRT1 or SIRT3-6. This compound has been shown to be active in HeLa cells by significantly increasing α-tubulin acetylation.
in vivo
SirReal2 (4 mg/kg, i.p., every 3 days for 28 days) combined with VS-5584 (4mg/kg, i.p., every 3 days for 28 days) leads to an extension of the survival time of mice and exhibits significant anti-tumor effects[3].
SirReal2 (50 mg/kg, i.p., every 3 days for 19 days) inhibits the expression of SIRT2, resumes NK cell tumor infltration and suppresses melanoma progression in WT mice[4].
| Animal Model: | mouse tumor xenograft model[3] |
| Dosage: | 4 mg/kg |
| Administration: | i.p., every 3 days for 28 days |
| Result: | Restrained the growth of subcutaneous xenografts combined with VS-5584 in vivo. |
