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

Advertisement

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
 
 
Advertisement
 

Recommended Videos

Quick guide to performing large-scale evaporation

Video

Benefit form a live demonstration of how to use industrial evaporator

WATCH NOW

2C or Not 2C: CYP2C Induction Studies for Successful Preclinical Risk Assessment (Webinar)

Video

This webinar will focus on CYP2C induction and will emphasize when to include CYP2C induction in a study, how to design the study to generate meaningful data and meet the regulatory requirements, what endpoints to measure, and how to interpret results.

WATCH NOW

Cleaning the Chemical Industry With a Hammer

Video

Throughout many years working in labs, the shocking impact of chemical enterprise on the environment has led chemist Thomas-Xavier Métro to explore the wonderful ways in which organic chemists can reduce their use of solvents, and help to protect our natural world. His talk hopes to show you how.

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