Molecular Formula | C24H27N5O3 |
Molar Mass | 433.5 |
Density | 1.239±0.06 g/cm3(Predicted) |
Melting Point | 189 - 191°C |
Solubility | DMSO (Slightly), Methanol (Slightly) |
Appearance | Solid |
Color | White to Off-White |
pKa | 9.47±0.20(Predicted) |
Storage Condition | -20°C Freezer |
MDL | MFCD22666356 |
In vitro study | ACY-1215 is a kind of hydroxamic acid derivatives. ACY-1215 was 12,10, and 11 times less effective at HDAC1, HDAC2, And HDAC3 (type I HDACs), respectively. ACY-1215 lowest activity for (IC50>1 μm) HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and for HDAC8(IC50 = 0.1 μm) it has slight activity. The IC50 value for the ACY-1215 effect on T-cell toxicity was 2.5 μm. ACY-1215 acts on the bone marrow (BM) environment to overcome the growth and survival of tumor cells conferred by BMSCs and cytokines. ACY-1215 in combination with Bortezomib induces synergistic anti-MM activity. ACY-1215, at very low doses, induced potent α-tubulin acetylation, and only at higher doses, triggered histone H3 and H4 histone lysine acetylation, its specific inhibitory effect on HDAC6 activity was confirmed. |
In vivo study | ACY-1215, in combination with Bortezomib, inhibited tumor growth and prolonged survival without significant adverse effects in two plasmacytoma models and a diffuse MM model. It has more significant anti-MM activity than used alone. ACY-1215 is easily absorbed by tumor tissue. In addition, the drug did not accumulate in the tumor tissue, and the acetylated α-tubulin of blood cells and tumor tissue decreased in parallel after 24 h of treatment. |