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, causing 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, and exhibits significant antitumor activity.

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

Alisertib (MLN 8237) induces mitotic spindle abnormalities and accumulation in MM cells, leading to inhibition of cell proliferation via apoptosis and senescence. It also enhances the expression of p53 and the tumor suppressor genes p21 and p27[1]. The diminished efficacy of Alisertib (MLN 8237) against the T217D/W277E Aurora A/TPX2 complex might be due to the increased ATP affinity caused by cofactor binding to Aurora A[2]. Furthermore, Alisertib (MLN 8237) demonstrates inhibitory effects on various tumor cell lines with IC 50 values ranging from 15 to 469 nM[4].

Alisertib (MLN 8237), administered at 30 mg/kg orally, significantly lowers tumor burden and enhances overall survival in a xenograft murine model of human multiple myeloma (MM)[1]. Additionally, when given orally at doses ranging from 3 to 30 mg/kg daily for a duration of three weeks, Alisertib demonstrated the capacity to inhibit tumor growth in models of solid tumor xenografts[4]. In a specific study involving nude mice with HCT-116 colon tumor xenografts, dosage levels of 3, 10, or 30 mg/kg administered orally once daily for three weeks yielded a dose-dependent tumor growth inhibition (TGI) of 43.3%, 84.2%, and 94.7%, respectively, indicating a potent anti-tumor activity across varying doses[4].