475216-25-2Relevant articles and documents
Aryl imidazole derivative and application thereof
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Paragraph 0649-0652, (2021/06/23)
The invention relates to an aryl imidazole derivative and application thereof. The aryl imidazole derivative is a compound shown as a formula (I) in the description or pharmaceutically acceptable salt thereof. The invention also discloses application of the aryl imidazole derivative in preparation of drugs for treating cancers. The invention further discloses application of the aryl imidazole derivative in preparation of drugs for treating diseases caused by EGFR mutation.
A Multifaceted Hit-Finding Approach Reveals Novel LC3 Family Ligands
Bruning, John M.,Burdick, Daniel J.,Cai, Jianping,Crawford, Terry,Decurtins, Willy,Dueber, Erin C.,Fang, Chunlin,Grubers, Felix,Helgason, Elizabeth,Holliday, Michael J.,Langley, Allyson,Li, Ke Sherry,Mulvihill, Melinda M.,Petersen, Ann,Popovych, Nataliya,Rougé, Lionel,Satz, Alexander Lee,Skelton, Nicholas,Song, Aimin,Staben, Steven T.,Steffek, Micah,Stoffler, Daniel,Strebel, Quentin,Tom, Jeffrey Y. K.,Wichert, Moreno,Xue, Jing
, (2022/01/19)
Autophagy-related proteins (Atgs) drive the lysosome-mediated degradation pathway, autophagy, to enable the clearance of dysfunctional cellular components and maintain homeostasis. In humans, this process is driven by the mammalian Atg8 (mAtg8) family of proteins comprising the LC3 and GABARAP subfamilies. The mAtg8 proteins play essential roles in the formation and maturation of autophagosomes and the capture of specific cargo through binding to the conserved LC3-interacting region (LIR) sequence within target proteins. Modulation of interactions of mAtg8 with its target proteins via small-molecule ligands would enable further interrogation of their function. Here we describe unbiased fragment and DNA-encoded library (DEL) screening approaches for discovering LC3 small-molecule ligands. Both strategies resulted in compounds that bind to LC3, with the fragment hits favoring a conserved hydrophobic pocket in mATG8 proteins, as detailed by LC3A-fragment complex crystal structures. Our findings demonstrate that the malleable LIR-binding surface can be readily targeted by fragments; however, rational design of additional interactions to drive increased affinity proved challenging. DEL libraries, which combine small, fragment-like building blocks into larger scaffolds, yielded higher-affinity binders and revealed an unexpected potential for reversible, covalent ligands. Moreover, DEL hits identified possible vectors for synthesizing fluorescent probes or bivalent molecules for engineering autophagic degradation of specific targets.
IMIDAZOLYL-IMIDAZOLES AS KINASE INHIBITORS
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Page/Page column 42-43, (2011/10/13)
Disclosed are compounds having the formula: wherein R1A, R1B, R2 and R3 are as defined herein, and methods of making and using the same.