SHP2 Inhibition Reveals Compensatory PI3K-AKT Activation in KRAS-Driven Pancreatic Cancer: Discovery of <b>SDUY104</b> and Rational Approaches for Combination Therapy
with BKM-120 exhibited superior antitumor activity compared to either monotherapy. Collectively, this study identifies a potent SHP2 allosteric inhibitor and delineates a critical compensatory signaling mechanism underlying resistance to SHP2-targeted therapy, providing proof-of-concept support for pancreatic cancer treatment.
Authors
- Zhiyi Yu (ORCID: https://orcid.org/0000-0001-6227-0610)
- Ruirong Tan (ORCID: https://orcid.org/0000-0003-1719-1416)
- Yu Zhang (ORCID: https://orcid.org/0000-0002-2358-0904)
- Chengchun Zhu
- Naining Zhang
- Yijie Zhu
- Li Yang
- Yaran Jin
- Chen Wang
- Zongrui Yu
- Kai Chen
- Xiaohan Ye
- Jinbo Yue
- Xiaoyu Liu
Institutions
- Academy of Medical Sciences (GB)
- Center for Drug Evaluation and Research (US)
- Shandong University of Traditional Chinese Medicine (CN)
- Shandong University (CN)
- Xuzhou Medical College (CN)
- State Administration of Traditional Chinese Medicine of the People's Republic of China (CN)
- Shandong Tumor Hospital (CN)
- Sichuan Academy of Traditional Chinese Medicine (CN)
- Shandong Academy of Pharmaceutical Sciences (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2026-06-09
- DOI
- https://doi.org/10.1021/acs.jmedchem.6c00836
- Primary Topic
- Protein Tyrosine Phosphatases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Shandong University
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province