| 产品介绍 |
MLN8237 (Alisertib) is a highly potent and selective Aurora A inhibitor with an IC50 of 1.2 nM, >200-fold selective towards structurally related Aurora B (IC50 of 396.5 nM). It does not have any significant activity against 205 other kinases. MLN8237 treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 treatment also causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM).In recent studies, MLN8237 induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. MLN8237 is currently in Phase II study for treatment of patients with ovarian, fallopian tube, or peritoneal carcinoma.
|
