MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors

Todd B Sells; Ryan Chau; Jeffrey A Ecsedy; Rachel E Gershman; Kara Hoar; Jessica Huck; David A Janowick; Vivek J Kadambi; Patrick J LeRoy; Matthew Stirling; Stephen G Stroud; Tricia J Vos; Gabriel S Weatherhead; Deborah R Wysong; Mengkun Zhang; Suresh K Balani; Joseph B Bolen; Mark G Manfredi; Christopher F Claiborne

doi:10.1021/ml500409n

MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors

ACS Med Chem Lett. 2015 Apr 22;6(6):630-4. doi: 10.1021/ml500409n. eCollection 2015 Jun 11.

Authors

Todd B Sells¹, Ryan Chau¹, Jeffrey A Ecsedy¹, Rachel E Gershman¹, Kara Hoar¹, Jessica Huck¹, David A Janowick¹, Vivek J Kadambi¹, Patrick J LeRoy¹, Matthew Stirling¹, Stephen G Stroud¹, Tricia J Vos¹, Gabriel S Weatherhead¹, Deborah R Wysong¹, Mengkun Zhang¹, Suresh K Balani¹, Joseph B Bolen¹, Mark G Manfredi¹, Christopher F Claiborne¹

Affiliation

¹ Takeda Pharmaceuticals International Co. , 40 Landsdowne Street, Cambridge, Massachusetts 02139, United States.

Abstract

The Aurora kinases are essential for cell mitosis, and the dysregulation of Aurora A and B have been linked to the etiology of human cancers. Investigational agents MLN8054 (8) and alisertib (MLN8237, 10) have been identified as high affinity, selective, orally bioavailable inhibitors of Aurora A that have advanced into human clinical trials. Alisertib (10) is currently being evaluated in multiple Phase II and III clinical trials in hematological malignancies and solid tumors.

Keywords: Alisertib; Aurora A kinase; MLN8054; MLN8237.