Quach, David published the artcileStrategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors, HPLC of Formula: 292170-96-8, the main research area is BCR ABL inhibitor lysine drug design; cancer; covalent inhibitors; lysine; proteomics; reversibility.
Targeted covalent inhibitors have re-emerged as validated drugs to overcome acquired resistance in cancer treatment. Herein, by using a carbonyl boronic acid (CBA) warhead, we report the structure-based design of BCR-ABL inhibitors via reversible covalent targeting of the catalytic lysine with improved potency against both wild-type and mutant ABL kinases, especially ABLT315I bearing the gatekeeper residue mutation. We show the evolutionarily conserved lysine can be targeted selectively, and the selectivity depends largely on mol. recognition of the non-covalent pharmacophore in this class of inhibitors, probably due to the moderate reactivity of the warhead. We report the first co-crystal structures of covalent inhibitor-ABL kinase domain complexes, providing insights into the interaction of this warhead with the catalytic lysine. We also employed label-free mass spectrometry to evaluate off-targets of our compounds at proteome-wide level in different mammalian cells.
Angewandte Chemie, International Edition published new progress about Antiproliferative agents. 292170-96-8 belongs to class amides-buliding-blocks, name is 5-Bromo-N,N-dimethylnicotinamide, and the molecular formula is C8H9BrN2O, HPLC of Formula: 292170-96-8.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics