Optimization of Covalent MKK7 Inhibitors <i>via</i> Crude Nanomole-Scale Libraries
Paul Gehrtz, Shir Marom, Mike Bührmann, Julia Hardick, Silke Kleinbölting, Amit Shraga, Christian Dubiella, Ronen Gabizon, Jan N. Wiese, Matthias Müller, Galit Cohen, Ilana Babaev, Khriesto A. Shurrush, Liat Avram, Efrat Resnick, Haim Barr, Daniel Rauh, Nir London
Abstract
conventional biological and biochemical methods such as western blots and liquid chromatography-mass spectrometry (LC-MS) labeling, and successfully co-crystallized. Two of these compounds showed over 20-fold increased inhibitory activity compared to the parental compound. This study demonstrates that high-throughput LSF of covalent inhibitors at the nanomole-scale level can be an auspicious approach in improving the properties of lead chemical matter.
Topics & Concepts
ChemistryCovalent bondCombinatorial chemistryAlkyneHigh-throughput screeningCycloadditionChemical synthesisClick chemistryAzideBiochemistryOrganic chemistryCatalysisIn vitroClick Chemistry and ApplicationsProtein Degradation and InhibitorsCAR-T cell therapy research