Open AccessComputational design of phosphoinositide 3-kinase gamma (PI3Kg) inhibitors as a newer therapy for rheumatoid arthritis
Author(s) -
Haiyan Tang,
Kai Ren,
Guanjie Wang,
Rong Zhang,
Long Zhang
Publication year - 2022
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v20i4.17
Subject(s) - rheumatoid arthritis , docking (animal) , virtual screening , pharmacology , medicine , toxicity , phosphoinositide 3 kinase , computational biology , bioinformatics , chemistry , signal transduction , pi3k/akt/mtor pathway , drug discovery , biology , immunology , biochemistry , nursing
Purpose: To develop a potential therapy for rheumatoid arthritis (RA) by altering factors involved in the pathogenesis of the disease.
Methods: Molecular docking simulation-based virtual screening was performed against phosphoinositide-3-kinase gamma (PI3Kg) to identify potential leads that may serve as anti-rheumatoid arthritic agents through their interactions and binding energies with the target receptor, followed by their optimization for improvement of their pharmacokinetics and toxicity profiles.
Results: Molecular docking simulation-based virtual screening and computational toxicity profiling predicted that the lead compounds ZINC04376856, ZINC01729526, ZINC01045089, ZINC03954520, ZINC01738764, and ZINC01163259 were potent PI3Kg inhibitors.
Conclusion: These lead compounds exert potent inhibitory effects on human PI3Kg receptor. Thus, they need to be experimentally validated for use in the development of novel drugs for treating RA in humans.