2. Academic Validation
  3. Structure-based artificial intelligence-aided design of MYC-targeting degradation drugs for cancer therapy

Structure-based artificial intelligence-aided design of MYC-targeting degradation drugs for cancer therapy

  • Biochem Biophys Res Commun. 2025 Jun 20:766:151870. doi: 10.1016/j.bbrc.2025.151870.
Donghua Liu 1,  Yize Jiang 1,  Bohan Ma 2,  Lei Li 3
Affiliations

Affiliations

  • 1 Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
  • 2 Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China. Electronic address: mabohan2009@sina.com.
  • 3 Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China. Electronic address: lilydr@163.com.
PMID: 40288261 DOI: 10.1016/j.bbrc.2025.151870
Abstract

The MYC protein is an oncoprotein that plays a crucial role in various cancers. Although its significance has been well recognized in research, the development of drugs targeting MYC remains relatively slow. In this study, we developed a novel MYC peptide inhibitor based on the MYC/MAX dimer structure, integrating artificial intelligence-assisted peptide drug design. Additionally, we introduced a chaperone-mediated Autophagy signal to construct a MYC-targeted degradation drug, MYC-LYSO. By incorporating nano-selenium delivery, we further formulated an enhanced MYC degradation agent, Se-MYC-LYSO. Se-MYC-LYSO demonstrated potent efficacy in inducing MYC degradation, inhibiting tumor cell proliferation, and promoting Apoptosis. Moreover, our findings indicate that the efficacy of Se-MYC-LYSO is dependent on the Autophagy pathway. These results provide a novel strategy for targeting MYC in Cancer therapy.

Keywords

Artificial intelligence-assisted; Chaperone-mediated autophagy; MYC; Peptide drug; Prostate cancer.

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