Small molecule drug discovery for glioblastoma treatment based on bioinformatics and cheminformatics approaches

Liya Feng; Sha Zhu; Jian Ma; Jing Huang; Xiaoyan Hou; Qian Qiu; Tingting Zhang; Meixia Wan; Juan Li

doi:10.3389/fphar.2024.1389440

Small molecule drug discovery for glioblastoma treatment based on bioinformatics and cheminformatics approaches

Front Pharmacol. 2024 Apr 12:15:1389440. doi: 10.3389/fphar.2024.1389440. eCollection 2024.

Authors

Liya Feng¹, Sha Zhu², Jian Ma³, Jing Huang¹, Xiaoyan Hou¹, Qian Qiu¹, Tingting Zhang¹, Meixia Wan¹, Juan Li¹

Affiliations

¹ Department of Basic Medical Sciences, College of Medicine, Longdong University, Qingyang, China.
² Gansu Province Medical Genetics Center, Gansu Provincial Maternal and Child Health Hospital, Lanzhou, China.
³ Key Lab of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Abstract

Background: Glioblastoma (GBM) is a common and highly aggressive brain tumor with a poor prognosis for patients. It is urgently needed to identify potential small molecule drugs that specifically target key genes associated with GBM development and prognosis. Methods: Differentially expressed genes (DEGs) between GBM and normal tissues were obtained by data mining the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene function annotation was performed to investigate the potential functions of the DEGs. A protein-protein interaction (PPI) network was constructed to explore hub genes associated with GBM. Bioinformatics analysis was used to screen the potential therapeutic and prognostic genes. Finally, potential small molecule drugs were predicted using the DGIdb database and verified using chemical informatics methods including absorption, distribution, metabolism, excretion, toxicity (ADMET), and molecular docking studies. Results: A total of 429 DEGs were identified, of which 19 hub genes were obtained through PPI analysis. The hub genes were confirmed as potential therapeutic targets by functional enrichment and mRNA expression. Survival analysis and protein expression confirmed centromere protein A (CENPA) as a prognostic target in GBM. Four small molecule drugs were predicted for the treatment of GBM. Conclusion: Our study suggests some promising potential therapeutic targets and small molecule drugs for the treatment of GBM, providing new ideas for further research and targeted drug development.

Keywords: ADMET; bioinformatics; glioblastoma; molecular docking; multi-omics data; therapeutic agents.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was partially supported by the Project of the Natural Science Foundation of Gansu Province, China (21JR11RM043 and 22JR5RM208). This work was also supported by the Innovation Fund Project of the Education Department of Gansu Province, China (2023B-212), and the Ph.D. Foundation Program of Longdong University, China (XYBYZK2310).