X‑ray Crystal
Structure-Guided Design and Optimization
of 7H‑Pyrrolo[2,3‑d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active
Monopolar Spindle 1 Inhibitor
Version 3 2021-05-06, 15:37Version 3 2021-05-06, 15:37
Version 2 2021-05-05, 12:35Version 2 2021-05-05, 12:35
Version 1 2021-05-04, 09:29Version 1 2021-05-04, 09:29
dataset
posted on 2021-05-06, 15:37authored byYounho Lee, Hyunkyung Kim, Haelee Kim, Ha Yeon Cho, Jun-Goo Jee, Kyung-Ah Seo, Jung Beom Son, Eunhwa Ko, Hwan Geun Choi, Nam Doo Kim, Ikyon Kim
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.