1047680-61-4Relevant articles and documents
Demonstrating Ligandability of the LC3A and LC3B Adapter Interface
Hartmann, Markus,Huber, Jessica,Kramer, Jan S.,Heering, Jan,Pietsch, Larissa,Stark, Holger,Odadzic, Dalibor,Bischoff, Iris,Fürst, Robert,Schr?der, Martin,Akutsu, Masato,Chaikuad, Apirat,D?tsch, Volker,Knapp, Stefan,Biondi, Ricardo M.,Rogov, Vladimir V.,Proschak, Ewgenij
, p. 3720 - 3746 (2021/05/04)
Autophagy is the common name for a number of lysosome-based degradation pathways of cytosolic cargos. The key components of autophagy are members of Atg8 family proteins involved in almost all steps of the process, from autophagosome formation to their selective fusion with lysosomes. In this study, we show that the homologous members of the human Atg8 family proteins, LC3A and LC3B, are druggable by a small molecule inhibitor novobiocin. Structure-activity relationship (SAR) studies of the 4-hydroxy coumarin core scaffold were performed, supported by a crystal structure of the LC3A dihydronovobiocin complex. The study reports the first nonpeptide inhibitors for these protein interaction targets and will lay the foundation for the development of more potent chemical probes for the Atg8 protein family which may also find applications for the development of autophagy-mediated degraders (AUTACs).
Design, synthesis, and biological studies of novel 3-benzamidobenzoic acid derivatives as farnesoid X receptor partial agonist
Hu, Lijun,Ren, Qiang,Deng, Liming,Zhou, Zongtao,Cai, Zongyu,Wang, Bin,Li, Zheng
supporting information, (2020/12/25)
Farnesoid X receptor (FXR), a bile acid-activated nuclear receptor, regulates the metabolism of bile acid and lipids as well as maintains the stability of internal environment. FXR was considered as a therapeutic target of liver disorders, such as drug-induced liver injury, fatty liver and cholestasis. The previous reported FXR partial agonist 6 was a suitable lead compound in terms of its high potent and low molecular size, while the docking study of compound 6 suggested a large unoccupied hydrophobic pocket, which might be provided more possibility of structure-activity relationship (SAR) study. In this study, we have performed comprehensive SAR and molecular modeling studies based on lead compound 6. All of these efforts resulted in the identification of a novel series of FXR partial agonists. In this series, compound 41 revealed the best activity and strong interaction with binding pocket of FXR. Moreover, compound 41 protected mice against acetaminophen-induced hepatotoxicity by the regulation of FXR-related gene expression and improving antioxidant capacity. In summary, these results suggest that compound 41 is a promising FXR partial agonist suitable for further investigation.
ARYL SULFONOHYDRAZIDES
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Page/Page column 41; 46; 57, (2016/12/26)
Compound of formula (I) wherein A is selected from (i), where RF1 is H or F; (ii); (iii) a N-containing C6 heteroaryl group; and B is (B), where X1 is either CRF2 or N, where RF2 is H or F; X2 is either CR3 or N, where R3 is selected from H, Me, CI, F OMe; X3 is either CH or N; X4 is either CRF3 or N, where RF3 is H or F; where only one or two of X1, X2, X3 and X4 may be N; and R4 is selected from I, optionally substituted phenyl, optionally substituted C5-6 heteroaryl; optionally substituted C1-6 aIkyI and optionally substituted C1-6 alkoxy, which are useful in the treatment of a condition ameliorated by the inhibition of MOZ.
BICYCLIC COMPOUND
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Paragraph 1027; 1028, (2014/09/03)
The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
