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

The Many Faces of the Thermo Scientific Vanquish Duo UHPLC System for Increased Productivity in Biopharma Analyses

Video

The Thermo Scientific Vanquish Duo UHPLC System can give analytical scientists a productivity boost for the many different analyses needs they might have to ensure fast and well-informed drug development.

WATCH NOW

In-operando X-ray diffraction (XRD) on a pouch cell battery

Video

This video shows a demonstration of how to set up in operando XRD experiments on full batteries.

WATCH NOW

Introducing the MALDI-2 on timsTOF fleX: MALDI-2, redefining ionization for >100x increased signal a

Video

timsTOF fleX is now available with the innovative and powerful MALDI-2 technology option. This post-ionization technique leads to both a significant boost in ion yields and reduction in ion suppression effects.

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