Triple-negative breast cancer (TNBC) is an aggressive breast-cancer subtype associated with poor prognosis and high relapse rates. Monopolar spindle 1 kinase (MPS1) is an apical dual-specificity protein kinase that is over-expressed in TNBC. We herein report a highly selective MPS1 inhibitor based on a 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. In vivo evaluation of candidate (9) is shown to effectively mitigate human TNBC cell proliferation.
Bibliographical noteFunding Information:
We thank the National Research Foundation of Korea (NRF-2018R1A6A1A03023718 and NRF-2020R1A2C2005961 to I.K.) for generous financial support.
© 2021 American Chemical Society.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery