2. Academic Validation
  3. Structure-based drug design of small-molecule c-Myc G-quadruplex binders

Structure-based drug design of small-molecule c-Myc G-quadruplex binders

  • J Comput Aided Mol Des. 2026 Jan 12;40(1):46. doi: 10.1007/s10822-025-00760-8.
Jian Gao 1 2,  Chenxi Xu 3 4,  Renjie Hong 3 4,  Guanghui Cheng 3 4,  Pingting Jia 3 4
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People's Hospital), Huainan, China. [email protected].
  • 2 School of Medicine, Anhui University of Science and Technology, Huainan, China. [email protected].
  • 3 The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People's Hospital), Huainan, China.
  • 4 School of Medicine, Anhui University of Science and Technology, Huainan, China.
PMID: 41524758 DOI: 10.1007/s10822-025-00760-8
Abstract

The c-Myc oncogene is crucial in tumorigenesis. Although it is a promising therapeutic target, its protein lacks a conventional drug-binding pocket, making it traditionally "undruggable". Recent studies show that the c-Myc promoter can form a G-quadruplex (G4) structure, which suppresses transcription and offers a new strategy for indirect inhibition. In this study, structure-based virtual screening was performed using the c-Myc G4 crystal structure to screen the ChemDiv compound library, aiming to identify small molecules that bind to the G4 structure. Candidate compounds were evaluated in preliminary in vitro assays for biological activity. The results showed that Y502-3888 binds to the c-Myc G4 and downregulates c-Myc expression at both mRNA and protein levels. Collectively, these findings support the potential of Y502-3888 as a c-Myc G4 binder for the treatment of multiple myeloma (MM), providing a foundation for future development of Anticancer agents targeting the c-Myc G4.

Keywords

G-quadruplex; Multiple myeloma; Virtual screening; c-Myc.

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