2. Academic Validation
  3. Discovery of JND3229 as a New EGFRC797S Mutant Inhibitor with In Vivo Monodrug Efficacy

Discovery of JND3229 as a New EGFRC797S Mutant Inhibitor with In Vivo Monodrug Efficacy

  • ACS Med Chem Lett. 2018 Oct 8;9(11):1123-1127. doi: 10.1021/acsmedchemlett.8b00373.
Xiaoyun Lu 1,  Tao Zhang 2 3 4,  Su-Jie Zhu 5,  Qiuju Xun 6,  Lingjiang Tong 2,  Xianglong Hu 1,  Yan Li 2,  Shingpan Chan 1,  Yi Su 2,  Yiming Sun 2,  Yi Chen 2,  Jian Ding 2,  Cai-Hong Yun 5,  Hua Xie 2,  Ke Ding 1
Affiliations

Affiliations

  • 1 International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.
  • 2 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
  • 3 School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China.
  • 4 School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
  • 5 Department of Biophysics and Peking University Institute of Systems Biomedicine, Peking University Health Science Center, Beijing 100191, China.
  • 6 Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.
PMID: 30429956 DOI: 10.1021/acsmedchemlett.8b00373
Abstract

EGFRC797S mutation inducing resistance against third generation EGFR inhibitor drugs is an emerging "unmet clinical need" for nonsmall cell lung Cancer patients. The pyrimidopyrimidinone derivative JND3229 was identified as a new highly potent EGFRC797S inhibitor with single digit nM potency. It also exhibited good in vitro and in vivo monodrug Anticancer efficacy in a xenograft mouse model of BaF3/EGFR19D/T790M/C797S cells. A high-resolution X-ray crystallographic structure was also determined to elucidate the interactions between JND3229 and EGFRT790M/C797S. Our study provides an important structural and chemical basis for future development of new generation EGFRC797S inhibitors as Anticancer drugs.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-119944
    99.78%, EGFRC797S Inhibitor