Discovery of SHR2415, a Novel Pyrrole-Fused Urea Scaffold ERK1/2 Inhibitor

  • ACS Med Chem Lett. 2022 Apr 1;13(4):701-706. doi: 10.1021/acsmedchemlett.2c00029.
Xin Li  1 ,  Ping Dong  1 ,  Ting Zhang  1 ,  Guodong Cai  1 ,  Yang Chen  1 ,  Huaide Dong  1 ,  Fang Yang  1 ,  Lei Zhang  1 ,  Yuchang Mao  1 ,  Jun Feng  1 ,  Chang Bai  1 ,  Feng He  1 ,  Weikang Tao  1
Affiliations
  • 1. R&D Center, Shanghai Hengrui Pharmaceutical Co., LTD., 279 Wenjing Road, Shanghai 200245, China.
PMID: 35450372 DOI: 10.1021/acsmedchemlett.2c00029
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.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-151367
    SHR2415
    98.04%, ERK1/2 Inhibitor
    target: ERK
    Research Areas: Cancer