Alisertib sodium (MLN 8237) is a potent and specific inhibitor (IC50 = 1.2 nM) of Aurora A kinase, an enzyme involved in cell division. By binding to Aurora A kinase, Alisertib sodium disrupts the formation of the mitotic spindle and causes abnormal cell division. At the molecular level, it acts on the AKT/mTOR/AMPK/p38 pathway, leading to the induction of apoptosis and autophagy in leukemic cells. This compound exhibits significant antitumor activity.

Aurora A:12.5 nM (IC50), Aurora B:396.5 nM (IC50)

Alisertib (MLN 8237) leads the MM cells to mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. Alisertib up-regulates p53 and tumor suppressor genes p21 and p27[1]. The decreased activity of Alisertib (MLN 8237) for the T217D/W277E Aurora A/TPX2 complex may reflect the increased affinity for ATP induced by cofactor binding to Aurora A[2]. Alisertib (MLN 8237) inhibits cell proliferation with IC 50 s ranging from 15 to 469 nM in different tumer cell lines[4].

Alisertib (MLN 8237) (30 mg/kg, p.o.) significantly reduces tumor burden and increases overall survival in xenograft-murine model of human-MM[1]. Alisertib (3-30 mg/kg; P.o.; once daily for 3 weeks) causes tumor growth inhibition in solid tumor xenograft models[4]. Animal Model: Nude mice bearing HCT-116 colon tumor xenograft[4]Dosage: 3, 10, or 30 mg/kg Administration: P.o.; once daily for 3 weeks Result: Resulted in a dose-dependent TGI (tumor growth inhibition) of 43.3%, 84.2%, and 94.7% for the 3, 10, and 30 mg/kg groups,respectively.