2. Academic Validation
  3. Discovery of SHR2415, a Novel Pyrrole-Fused Urea Scaffold ERK1/2 Inhibitor

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

Affiliation

  • 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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-151367
    98.63%, ERK1/2 Inhibitor
    ERK