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Published on: November 9, 2020
Structure-based artificial intelligence-aided design of MYC-targeting degradation drugs for cancer therapy
Donghua Liu1, Yize Jiang1, Bohan Ma1
1Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
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.
Insights
Researchers developed Se-MYC-LYSO, a novel drug targeting the MYC oncoprotein. This innovative agent effectively degrades MYC, inhibits cancer cell growth, and induces apoptosis, offering a new cancer therapy strategy.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The MYC protein is a critical oncoprotein implicated in numerous cancers.
- Despite its known role, developing effective MYC-targeting drugs has been challenging.
- Targeting MYC degradation presents a promising therapeutic avenue.
Purpose of the Study:
- To design and develop a novel peptide inhibitor targeting the MYC/MAX dimer.
- To engineer a MYC-targeted degradation drug incorporating a chaperone-mediated autophagy signal (MYC-LYSO).
- To formulate an enhanced MYC degradation agent using nano-selenium delivery (Se-MYC-LYSO).
Main Methods:
- Utilized artificial intelligence-assisted peptide drug design based on the MYC/MAX dimer structure.
- Incorporated a chaperone-mediated autophagy signal to create MYC-LYSO.
- Employed nano-selenium for drug delivery to formulate Se-MYC-LYSO.
Main Results:
- Se-MYC-LYSO effectively induced MYC degradation in cancer cells.
- The agent demonstrated significant inhibition of tumor cell proliferation.
- Se-MYC-LYSO promoted cancer cell apoptosis, with efficacy dependent on the autophagy pathway.
Conclusions:
- Se-MYC-LYSO represents a potent MYC degradation agent with therapeutic potential in cancer.
- The study highlights the importance of the autophagy pathway in mediating the drug's efficacy.
- This work provides a novel strategy for targeting MYC in cancer treatment through targeted degradation.
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