Posters
Presenting Author Academic/Professional Position
Fellow
Academic Level (Author 1)
Fellow
Discipline/Specialty (Author 1)
Immunology and Microbiology
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Metarrestin (ML246) is an orally bioavailable synthetic molecule that selectively disrupts the perinucleolar compartment (PNC) structure, and it has showed promise in preclinical studies for metastatic cancer therapy. However, the precise molecular mechanism of ML246 remains poorly understood. We investigated the topological and protein interaction network (PIN) analyses of ML246 to determine the molecular mechanism of ML246. To determine the regulatory effect of ML246 on the rewired PIN of ML246, an intercom was constructed using 25 oncogenic key proteins. These proteins were selected using the reverse pharmacophore matching approach (based on a fit score > 0.502) using the STRING database and Cytoscape tool.ML246-rewired PIN exhibited a scale-free topology and demonstrated substantial connectivity with the biological system. After modularization, the rewired PIN yielded 10 sub- clusters from which the MCODE plugin was able to identify the most critical seed proteins in the intercom; 14 enriched signaling pathways were obtained by using the ClueGO plugin for pathway enrichment. Most of the pathways were associated with human disease groups, like cancer. Finally, identifying major regulatory proteins of the ML246-rewired PIN was finalized by examining topological properties, including bottleneck analysis, GO term/pathways analysis, degree analysis, molecular docking, and dynamics studies. This study suggests a proficient approach to exploring ML246's potential mechanistic actions and paves the way for novel drug development prospects in clinical settings.
Recommended Citation
Sharma, Bhuvnesh P.; Singh, Himanshu N.; Singh, Bhupesh; Parashar, Deepak; Roy, Kuldeep K.; Yallapu, Murali M.; Chauhan, Subhash C.; and Kashyap, Vivek K., "Using network pharmacology to systematically deduce the molecular mechanism of the selective perinucleolar compartment inhibitor ML246" (2025). Research Symposium. 34.
https://scholarworks.utrgv.edu/somrs/2025/posters/34
Included in
Bioinformatics Commons, Biotechnology Commons, Medicine and Health Sciences Commons, Microbiology Commons
Using network pharmacology to systematically deduce the molecular mechanism of the selective perinucleolar compartment inhibitor ML246
Metarrestin (ML246) is an orally bioavailable synthetic molecule that selectively disrupts the perinucleolar compartment (PNC) structure, and it has showed promise in preclinical studies for metastatic cancer therapy. However, the precise molecular mechanism of ML246 remains poorly understood. We investigated the topological and protein interaction network (PIN) analyses of ML246 to determine the molecular mechanism of ML246. To determine the regulatory effect of ML246 on the rewired PIN of ML246, an intercom was constructed using 25 oncogenic key proteins. These proteins were selected using the reverse pharmacophore matching approach (based on a fit score > 0.502) using the STRING database and Cytoscape tool.ML246-rewired PIN exhibited a scale-free topology and demonstrated substantial connectivity with the biological system. After modularization, the rewired PIN yielded 10 sub- clusters from which the MCODE plugin was able to identify the most critical seed proteins in the intercom; 14 enriched signaling pathways were obtained by using the ClueGO plugin for pathway enrichment. Most of the pathways were associated with human disease groups, like cancer. Finally, identifying major regulatory proteins of the ML246-rewired PIN was finalized by examining topological properties, including bottleneck analysis, GO term/pathways analysis, degree analysis, molecular docking, and dynamics studies. This study suggests a proficient approach to exploring ML246's potential mechanistic actions and paves the way for novel drug development prospects in clinical settings.
