Discovery of SHR2415, a Novel Pyrrole-Fused Urea Scaffold ERK1/2 Inhibitor.
ACS Med Chem Lett
; 13(4): 701-706, 2022 Apr 14.
Article
em En
| MEDLINE
| ID: mdl-35450372
ABSTRACT
ERK1/2 kinase is a key downstream node of the RAS-RAF-MEK-ERK signaling pathway. A highly potent and selective ERK1/2 inhibitor is a promising option for cancer treatment that will provide a potential solution for overcoming drug resistance. Herein we designed and synthesized a novel scaffold featuring a pyrrole-fused urea template. The lead compound, SHR2415, was shown to be a highly potent ERK1/2 inhibitor that exhibited high cell potency based on the Colo205 assay. In addition, SHR2415 displayed favorable PK profiles across species as well as robust in vivo efficacy in a mouse Colo205 xenograft model.
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MEDLINE
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En
Ano de publicação:
2022
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Article