Alisertib (MLN8237, 1028486-01-2) is a highly selective and potent (IC50 = 1 nM) cell permeable inhibitor of Aurora A with off-target binding at GABAA (IC50 = 490 nM).1 It disrupts the Aurora A-Myc complex leading to Myc degradation2 in Myc amplified neuroblastomas3 and p53-mutant human hepatocellular carcinoma cell4. Alisertib has been found to induce apoptosis and autophagy in breast cancer5 and melanoma6 cells via suppression of activation of the p38 MAPK pathway.
1) Sells et al. (2015), MLN8054 and Alisertib (MLN8237):Discovery of Selective Oral Aurora A Inhibitors; ACS Med. Chem. Lett. 6 630
2) Richards et al. (2016), Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors; Proc. Natl. Acad. Sci. USA 113 13726
3) Brockmann et al. (2013), Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma; Cancer Cell 24 75
4) Dauch et al. (2016), A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer; Nat. Med. 22 744
5) Li et al. (2015), The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells; Drug Des. Devel. Ther. 16 1627
6) Shang et al. (2017), Alisertib promotes apoptosis and autophagy in melanoma through p38 MAPK-mediated aurora a signaling; Oncotarget 8 107076