Rational adaptation of L3MBTL1 inhibitors to create small-molecule Cbx7 antagonists.

We report here our efforts to create low-molecular weight inhibitors of Cbx7 by making rational structural adaptations of inhibitors of a different methyl reader protein, L3MBTL1-inhibitors that had previously been reported to be inactive against Cbx7. We evaluated each new inhibitor for Cbx7 inhibition by a fluorescence-polarization assay (FP assay), and also confirmed binding of selected inhibitors to Cbx7 by saturation-transfer difference NMR (STD NMR) spectroscopy. This work identified multiple small-molecule inhibitors with modest (257-500 μM) potency.
PMID: 31254321 [PubMed - as supplied by publisher]

Source: ChemMedChem - June 27, 2019 Category: Chemistry Authors: Simhadri C, Daze KD, Douglas SF, Milosevich N, Monjas L, Dev A, Brown TM, Hirsch AKH, Wulff JE, Hof F Tags: ChemMedChem Source Type: research