Association of temozolomide with progressive multifocal leukoencephalopathy: a disproportionality analysis integrated with network pharmacology

ABSTRACT

Background

Temozolomide (TMZ) is an alkylating agent approved for the management of glioblastoma. The TMZ is not known for progressive multifocal leukoencephalopathy (PML). The main objective of the current study is to find out the association of TMZ with PML using disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data integrated with network pharmacological approaches.

Research design and methods

OpenVigil tool was used to query the FAERS database. The disproportionality measures were calculated. The network has been constructed using Cytoscape. Finally, the possible binding interactions were studied using Glide, Schrödinger Inc.

Results

A total number of 3502 cases of PML were reported in the FAERS database. Out of these, 10 cases were found with TMZ. The subgroup analysis results have shown a greater number of cases in females. The network has indicated the involvement of human mitogen-activated protein kinase, 3-phosphoinositide-dependent protein kinase 1 protein, human mTOR complex protein, phosphatidylinositol 4,5-bisphosphate 3-kinase protein, and glycogen synthase kinase-3 beta protein. The docking results have indicated good interactions of TMZ with active site of glycogen synthase kinase-3 beta and mitogen-activated protein kinase 1 as compared to other identified targets.

Conclusion

The PML is identified as novel signal with temozolomide.

KEYWORDS:

• Temozolomide
• progressive multifocal leukoencephalopathy
• OpenVigil 2.1
• disproportionality analysis
• network pharmacology
• docking study

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The author would like to acknowledge Vice-chancellor of Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi-110017, for his continuous support, motivation, and providing necessary facilities to carry out this work.

Authors’ contributions

V Bhati has conducted a study and prepared the first draft; V Lather has performed docking studies; R Sharma revision of manuscript; D Pandita revision of the manuscript; A Kumar have designed and revised the manuscript. All authors reviewed the manuscript.

Ethics

The data is available publicly in FAERS database. Therefore, permission is not required.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2278682

Additional information

Funding

This paper was not funded.