This week, NTRC published results from its TTK (Mps1) drug discovery programme in the Journal of Molecular Biology.
TTK is a promising new drug target for the treatment of aggressive cancers such as triple-negative breast cancer. NTRC combined the ResidenceTimer™ platform for determination of binding kinetics with protein crystallography to develop inhibitors with a unique mechanism of action.
Compared to reference inhibitors, NTRC’s TTK inhibitors bind in a unique ‘lysine trap’ binding mode that shifts the so-called glycine rich loop in TTK and locks the catalytic lysine in a dysfunctional state. As a result of these stabilizing rearrangements, the inhibitors have long target residence times which translate into very potent antiproliferative activities that rival those of classic cytotoxic therapy. This was measured in NTRC’s Oncolines™ cancer cell line panel. The unique properties and potent activity open up new and specific applications for TTK inhibitors in cancer treatment.
Follow this link to access the full article.