- Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation
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Dysregulation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of β-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.
- Yang, Wei,Li, Yingjun,Ai, Yong,Obianom, Obinna N.,Guo, Dong,Yang, Hong,Sakamuru, Srilatha,Xia, Menghang,Shu, Yan,Xue, Fengtian
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p. 11151 - 11164
(2019/12/27)
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- Copper(I)-catalyzed cycloaddition of 4-bromosydnones and alkynes for the regioselective synthesis of 1,4,5-trisubstituted pyrazoles
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Copper-catalyzed cycloaddition of alkynes with 4-bromosydnones provides a convenient, mild, and regioselective method for the synthesis of a wide range of bromopyrazoles. The broad functional group tolerance of the cycloaddition reaction and further palla
- Decuypere, Elodie,Specklin, Simon,Gabillet, Sandra,Audisio, Davide,Liu, Hui,Plougastel, Lucie,Kolodych, Sergii,Taran, Frédéric
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supporting information
p. 362 - 365
(2015/01/30)
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- Herbicidal and algicidal 1,5-disubstituted-1H-pyrazole-4-carboxamides
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1,5-Disubstituted-1H-pyrazole-4-carboxamide derivatives, useful as herbicides and aquatic algicides.
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