Alisertib
Aurora A inhibitor; Destablizes Myc / Alisertib (MLN8237) 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.
Biochemicals & reagents
1028486-01-2
MLN8237
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
-20°C
TARGET: Kinase -- PATHWAY: Myc; Apoptosis inducer; Autophagy; Cell cycle -- RESEARCH AREA: Cell death -- DISEASE AREA: Cancer