Oss, November, 10th, 2017 – At GTC Bio’s European Pharma Summit to be held in Berlin on 16 and 17 November, Dr. Guido Zaman will present on NTRC’s TTK drug discovery program in a scientific session on “Target residence time in kinase drug development”.
Target residence time, that is the time a compound resides on it target, is thought to be a more important determinant of the biological activity of small molecule kinase inhibitors than their potency in enzyme assays, or their binding affinity at equilibrium. Dr. Zaman will present data on twelve TTK inhibitors from different chemical series, comprising NTRC proprietary compounds and compounds designed . Parallel testing showed that the cellular activity of these TTK inhibitors correlates with their binding affinity to TTK and, more strongly, with target residence time. X-ray structures and thermal stability experiments revealed that NTRC’s kinase inhibitor series induce a unique conformational shift in TTK that disrupts its catalytic machinery. This knowledge was applied to design a series of novel TTK inhibitors with unprecedented cellular potency. In addition, Dr. Zaman will present the discovery of a prospective drug sensitivity biomarker for TTK inhibitors using NTRC’s Oncolines™ cell line panel profiling.
Symposium: Kinase inhibitors in drug discovery
Title: Target residence-guided optimization of kinase
Presenter: Dr. Guido Zaman
Date and Time: Thursday, November 16th, 6:40 PM
- Uitdehaag et al. (2017) Target residence time-guided optimization on TTK kinase results in inhibitors with potent anti-proliferative activity. Journal of Molecular Biology, 429, 2211-2230.
- Zaman et al. (2017) TTK inhibitors as a targeted therapy for CTNNB1 (β-catenin) mutant cancers. Molecular Cancer Therapeutics, advanced online, July 27, 2017.
NTRC is a precision medicine company dedicated to the development of new anti-cancer drugs. NTRC facilitates the development of novel therapies by providing cancer cell line profiling services (Oncolines™, OncolinesProfiler™, SynergyFinder™ and SynergyScreen™) and target residence time measurements for protein kinases (ResidenceTimer™) on a fee-for-service basis. NFK GreenScreen™, an assay read-out for the cancer immunotherapy drug targets IDO1 and TDO, is supplied to clients globally. NTRC has internal drug discovery programs on TTK, IDO1 and TDO. For more information please visit www.ntrc.nl or contact [email protected]