ImproveCRC

Potent and sustained inhibition of p38 for the treatment of colorectal cancer

01/05/2018 to 01/05/2021

Advanced Colorectal Cancer (CRC) represents a major health problem with very limited therapeutic options and a dismal prognosis. It was recently reported that genetic ablation of Mapk14 (p38α) in CRC mouse models results in pronounced tumor remissions and improved survival of tumor bearing mice. Available p38α inhibiting compounds do not mimic the phenotype observed upon genetic Mapk14 ablation due to incomplete pathway inhibition, thus pointing out a strong need for compounds with extreme (picomolar) activity, strongly enhanced or irreversible target residence time and high selectivity. Building upon our recent description of the development of such inhibitors, we are now aiming to advance such compounds into proof of concept studies and to test their potential in predictive CRC mouse models. These studies are prerequisite for later first in man studies in humans.