We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience, read our Cookie Policy

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

Investigating the World's Lightest Solid

Video

Aerogels are the world's lightest (least dense) solids. They are also excellent thermal insulators and have been used in numerous Mars missions and the Stardust comet particle-return mission. The focus of this video is silica aerogels, though graphene aerogels are now technically the lightest.

WATCH NOW

Agilent 8700 LDIR chemical imaging system – What’s in the tablet?

Video

Learn how to minimize the time you spend on sample analysis and data review—so you can increase productivity and minimize costs.

WATCH NOW

Looking for active responders to oxidative stress at the U. of Alabama | Behind the Science, S3 Ep10

Video

In Behind the Science, Jen visits the Redox Lab at the University of Alabama to see the difference between active and non-active responders for to oxidative stress for high-fat diets. Can lycopene help?

WATCH NOW

 

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