Design, Synthesis and Biological Evaluation of ERK Inhibitors with Isoindolin-1-one Structure

doi:10.7503/cjcu20250123

Chem. J. Chinese Universities

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Design, Synthesis and Biological Evaluation of ERK Inhibitors with Isoindolin-1-one Structure

ZHANG Lingzhi^1*, JU Qiurong², GUAN Zhe³, ZHU Qihua², ZHANG Tingting¹, YANG Shiqin¹, XU Yungen²

1. College of Biopharmacy, Suzhou Chien-Shiung Institute of Technology
2. Department of Medical Chemistry, China Pharmaceutical University
3. INNOVENT BIOLOGICS (SUZHOU) CO. LTD.

Received:2025-04-25 Revised:2025-06-24 Online First:2025-06-25 Published:2025-06-25
Contact: Yungen Xu
Supported by:
Supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 23KJB350008) and Taicang Research Foundation for Basic Research Plan General Project (No. TC2024JC21)

Abstract

Abstract: Using the ERK inhibitor EK-I-22 and MK-8353 as the lead compounds, 14 compounds were designed and synthesized by pharmacophore fusion strategy. Preliminary pharmacological activity assessments revealed that compounds 19a(16 nM), 19b(15 nM), 19e(20 nM), 30a(19 nM), and 30b(56 nM) exhibited significant inhibitory activity against ERK2 kinase. Notably, compound 30b demonstrated moderate inhibitory effects against four human tumor cell lines (Colo-205, A375, A2058, and HT-29).

Key words: MAPK pathway, ERK inhibitors, Synthesis, Antitumor activity

CLC Number:

O626.4

TrendMD:

ZHANG Lingzhi, JU Qiurong, GUAN Zhe, ZHU Qihua, ZHANG Tingting, YANG Shiqin, XU Yungen. Design, Synthesis and Biological Evaluation of ERK Inhibitors with Isoindolin-1-one Structure[J]. Chem. J. Chinese Universities, doi: 10.7503/cjcu20250123.

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Design, Synthesis and Biological Evaluation of ERK Inhibitors with Isoindolin-1-one Structure

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