Discovery of Potent and Selective Inhibitors of Monopolar Spindle 1 (MPS1) Kinase

Video   Oct 06, 2016

 

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 tumours with chromosomal instability and aneuploidy; PTEN-deficient breast tumour cells are particularly dependent upon MPS1 for their survival making it a target of significant interest in oncology. In this talk I will present the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition. Our research yielded the potent and selective chemical tool compound CCT251455, which stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP- and substrate peptide-binding. CCT251455 displays a favorable oral pharmacokinetic profile and shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model. It is therefore an attractive tool compound to further elucidate the therapeutic potential of MPS1 inhibition.

 
Company Information
 
 
 

Recommended Videos

Behind the Science, S2 Ep7: Lauren Mullin and the flight of the bees

Video

What's the buzz about bees? Lauren Mullin talks about how she performed an experiment to test samples of bee pollen for exposure to the neonicotinoid pesticide imidacloprid, which may be a cause of colony collapse disorder

WATCH NOW

Thermo Scientific™ NanoDrop™ One Microvolume UV-Vis spectrophotometer

Video

Quantify and qualify DNA, RNA, and protein samples with only 1-2 µL and have full-spectral data in seconds using the Thermo Scientific™ NanoDrop™ One Microvolume UV-Vis spectrophotometer.

WATCH NOW

MicroCal PEAQ-ITC: The gold standard for measuring binding affinities

Video

This video describes the 4 main reasons why MicroCal PEAQ-ITC is the ideal instrument for measuring binding affinities.

WATCH NOW

 

Comments | 0 ADD COMMENT

Like what you just watched? You can find similar content on the communities below.

Analysis & Separations Drug Discovery

To personalize the content you see on Technology Networks homepage, Log In or Subscribe for Free

LOGIN SUBSCRIBE FOR FREE