Alisertib | Potent and selective inhibitor of Aurora A / Destabilizes Myc

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 GABA_A (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.

References/Citations

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