System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson’s disease: a network pharmacology and in-silico evaluation.

System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson’s disease: a network pharmacology and in-silico evaluation.

Publication date: Oct 08, 2024

IMPHY000797 derivatives have been well known for their efficacy in various diseases. Moreover, IMPHY000797 derivatives have been found to modulate such genes involved in multiple neurological disorders. Hence, this study seeks to identify such genes and the probable molecular mechanism that could be involved in the pathogenesis of Parkinson’s disease. The study utilized various biological tools such as DisGeNET, STRING, Swiss target predictor, Cytoscape, AutoDock 4. 2, Schrodinger suite, ClueGo, and GUSAR. All the reported genes were obtained using DisGeNET, and further, the common genes were incorporated into the STRING to get the KEGG pathway, and all the data was converted to a protein/pathway network via Cytoscape. The clustering of the genes was performed for the gene-enriched data using two-sided hypergeometrics (p-value). The binding affinity of the IMPHY000797 was verified with the highest regulated 25 proteins via utilizing the “Monte Carlo iterated search technique” and the “Emodel and Glide score” function. Three thousand five hundred eighty-three genes were identified for Parkinson’s disease and 31 genes for IMPHY000797 compound, among which 25 common genes were identified. Further, the “FOXO-signaling pathway” was identified to be a modulated pathway. Among the 25 proteins, the highest modulated genes and highest binding affinity were exhibited by SIRT3, FOXO1, and PPARGC1A with the compound IMPHY000797. Further, rat toxicity analysis provided the efficacy and safety of the compound. The study was required to identify the probable molecular mechanism, which needs more confirmation from other studies, which is still a significant hit-back.

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Concepts Keywords
Biology Animals
Parkinson Computer Simulation
Pathogenesis Gene Regulatory Networks
Pharmacology Humans
Swiss IMPHY000797
In-silico studies
Network Pharmacology
Network pharmacology
Neuroprotection
Parkinson Disease
Parkinson’s disease
Protein Interaction Maps
Rats
Signal Transduction
Systems Biology

Semantics

Type Source Name
disease MESH Parkinson’s disease
disease MESH neurological disorders
disease MESH pathogenesis
pathway KEGG FoxO signaling pathway
drug DRUGBANK Oxygen
disease MESH oxidative stress
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH Alzheimer’s disease
drug DRUGBANK Coenzyme M
drug DRUGBANK Water
drug DRUGBANK Amino acids
drug DRUGBANK Nadide
pathway KEGG Longevity regulating pathway
pathway KEGG Thyroid hormone signaling pathway
drug DRUGBANK Serine
drug DRUGBANK Alpha-Linolenic Acid
drug DRUGBANK L-Aspartic Acid
drug DRUGBANK L-Threonine
drug DRUGBANK L-Asparagine
drug DRUGBANK L-Isoleucine
drug DRUGBANK L-Tryptophan
drug DRUGBANK L-Leucine
drug DRUGBANK Glycine
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Glutamic Acid
drug DRUGBANK L-Lysine
drug DRUGBANK L-Valine
drug DRUGBANK L-Tyrosine
drug DRUGBANK L-Arginine
disease MESH death
disease MESH Parkinsonism
drug DRUGBANK Sertraline
pathway REACTOME Methylation
drug DRUGBANK Scutellaria baicalensis root
disease MESH neuroinflammation
drug DRUGBANK Diethylstilbestrol
pathway REACTOME Metabolism
disease MESH brain diseases
disease MESH Mitochondrial dysfunction
disease MESH Lifestyle
disease MESH Chronic diseases
drug DRUGBANK Angiotensin II
disease MESH clinical significance
pathway REACTOME Reproduction
pathway KEGG Parkinson disease
pathway REACTOME Signal Transduction

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