292170-96-8Relevant articles and documents
Strategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors**
Anantharajan, Jothi,Baburajendran, Nithya,Foo, Klement,Joy, Joma K.,Keller, Thomas H.,Kwek, Perlyn Z.,Li, Rong,Liu, Boping,Poulsen, Anders,Quach, David,Retna, Priya,Tang, Guanghui,Tee, Doris H. Y.,Wee, John L. K.,Yang, Wan-Qi,Yao, Shao Q.,Zhang, Chong-Jing
supporting information, p. 17131 - 17137 (2021/06/28)
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 molecular 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.
IMIDAZOLE DERIVATIVE
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Page/Page column 99, (2009/09/05)
A CB2 receptor modulator comprising an imidazole derivative represented by the general formula (I): [wherein, R1 represents optionally substituted lower alkyl or the like; R2 represents optionally substituted cycloalkyl or the like; R3 represents optionally substituted aryl or the like; and n represents an integer of 0 to 3] or a pharmaceutically acceptable salt thereof as an active ingredient, and the like are provided.
Pyrrolo-pyridine kinase modulators
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Page/Page column 27, (2010/02/15)
The present invention provides novel pyrrolo-pyridine kinase modulators and methods of using the novel pyrrolo-pyridine kinase modulators to treat diseases mediated by kinase activity.