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Discovery and in vivo profiling of the MPS1 inhibitor and Phase 1 candidate CCT289346/BOS172722


Discovery and in vivo profiling of the MPS1 inhibitor and Phase 1 candidate  CCT289346/BOS172722
Dr Swen Hoelder
Cancer Research UK Cancer Therapeutics Unit at the Institute of Cancer Research

MPS1 (also known as TTK), is a dual-specificity protein kinase and one of the main components of the spindle assembly checkpoint. Cancer cells heavily rely on MPS1 to cope with aneuploidy resulting from aberrant numbers of chromosomes and the kinase has been found to be upregulated in a large number of tumor types making it an attractive cancer target.

In this webinar we will focus on two aspects of our MPS1 drug discovery project. The first aspect is the discovery of CCT289346, our preclinical candidate currently undergoing early clinical development. The medicinal chemistry effort started with an azaindole screening hit. Structure based optimization led to compounds with greatly improved potency and selectivity exemplified by the chemical probe CCT251455. In addition, using knowledge based design we discovered a second class of MPS1 inhibitors, the pyridopyrimidines. Multidimensional optimization of this class ultimately yielded CCT289346/BOS172722. CCT289346/BOS172722 shows excellent potency, kinase selectivity, and ADME properties. We will describe key medicinal chemistry challenges on route to the drug, particularly optimization of metabolic stability.

The second part of this webinar will be focused on our efforts to identify specific patient populations and tumor types, that may maximally benefit from treatment with MPS1 inhibitors. We will describe our work to identify such patient populations, leading to clinical hypotheses that are underpinned by in vivo data and that we have recently started to test in early clinical trials.

Attend this webinar to learn about:

  • Multidimensional medicinal chemistry optimization approaches for the identification of drug candidates.
  • Hypothesis driven identification of clinical patient populations for MPS1 inhibitors.
  • Drug discovery in an academic setting.


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