2. Academic Validation
  3. Disrupted target binding with acryloyl group as potential Bcr-Abl/C-Src dual kinase inhibitor optimization strategies with maintained antitumor activity

Disrupted target binding with acryloyl group as potential Bcr-Abl/C-Src dual kinase inhibitor optimization strategies with maintained antitumor activity

  • Bioorg Med Chem Lett. 2025 Jan 13:119:130105. doi: 10.1016/j.bmcl.2025.130105.
Ching Lin 1,  Hsin-Yi Chiang 1,  Grace Shiahuy Chen 2,  Ji-Wang Chern 1,  Chao-Wu Yu 3
Affiliations

Affiliations

  • 1 National Taiwan University, School of Pharmacy, College of Medicine, Taipei 100 Taiwan.
  • 2 Department of Applied Chemistry, Providence University, Taichung 43301 Taiwan.
  • 3 National Taiwan University, School of Pharmacy, College of Medicine, Taipei 100 Taiwan. Electronic address: stifenyu@ntu.edu.tw.
PMID: 39814085 DOI: 10.1016/j.bmcl.2025.130105
Abstract

Current CML treatments often suffer from undesired side effects. Herein we report the computation-assisted optimization of Bcr-Abl/C-Src dual kinase inhibitor. We surmised the improved toxicity profile was achieved via disrupted ligand-target binding. The development of compound 21b highlighted our strategy with ∼1000-fold weaker Bcr-Abl/C-Src inhibition but same level of antiproliferation compared to that of bosutinib. We demonstrated that the introduction of acryloyl group could serves as a potential strategy to maintain antitumor activity.

Keywords

Acryloyl group; Anticancer; Kinase inhibitor; Quinolone.

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