Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1).
AuthorsNaud S, Westwood IM, Faisal A, Sheldrake P, Bavetsias V, Atrash B, Cheung KM, Liu M, Hayes A, Schmitt J, Wood A, Choi V, Boxall K, Mak G, Gurden M, Valenti M, de Haven Brandon A, Henley A, Baker R, McAndrew C, Matijssen B, Burke R, Hoelder S, Eccles SA, Raynaud FI, Linardopoulos S, van Montfort RL, Blagg J,
Journal
PubMed ID24256217
'The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, ... More
Human Mps1 protein kinase is required for centrosome duplication and normal mitotic progression.
AuthorsFisk HA, Mattison CP, Winey M,
JournalProc Natl Acad Sci U S A
PubMed ID14657364
The mitotic spindle is essential for the maintenance of genetic stability, and in budding yeast its assembly and function depend on the Mps1 protein kinase. Mps1p is required for centrosome duplication and the spindle checkpoint. Several recent reports demonstrate that vertebrate Mps1 proteins regulate the spindle checkpoint, but reports conflict ... More