Molecular Docking and Fingerprint -based Vertual Screning Reveal the Anticancer Drug Ribociclibas a Promising Drug Jak1 Inhibitor in Rheumatoid Arthritis
Year: 2025
Type: article
Abstract: Dysregulated cytokine signalling via the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway is the main cause of rheumatoid arthritis (RA), a chronic autoimmune disease marked by ongoing synovial inflammation and joint damage. JAK1 is a prospective therapeutic target because it is one of the JAK family members that is essential in mediating pro-inflammatory responses. In order to find new JAK1 inhibitors among FDA-approved medications, the current work used a computational drug repurposing strategy that combined molecular docking and virtual screening based on Morgan fingerprints. Nineteen structurally comparable candidates were obtained from the DrugBank database using tofacitinib as a reference molecule. The anticancer medication Ribociclib had the highest binding affinity (–9.1 kcal/mol) against JAK1, outperforming Tofacitinib (–8.8 kcal/mol), according to docking tests conducted using CB-Dock2.Strong target engagement was confirmed by interaction analysis, which showed robust hydrogen bonding and hydrophobic interactions with important active site residues such as Leu959, Glu966, and Asp1003. The PDB-REDO model refinement enhanced structural precision, boosting the trustworthiness of docking results. Additionally, Ribociclib's pharmacokinetic profile as a systemically active medication is consistent with its strong gastrointestinal absorption and restricted blood–brain barrier permeability, according to the BOILED-Egg model analysis. All of these results point to Ribociclib as a viable repurposing option for JAK1 inhibition in rheumatoid arthritis, deserving of additional in vitro and in vivo validation to investigate its safety and therapeutic efficacy in inflammatory conditions.
Author: Mr. Jagdish S. Belekar*, Mr. Avdhut K. Dukandar, Ms. Sanika S. kokane, Ms. Shruti A. Ambale, Ms.Vaishnavi P. Atigre
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7091443919
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