Unveiling the Adjuvant Therapeutic Potential of Dabrafenib Derivatives in Lung Adenocarcinoma via in Silico Multi-Targeting of B-RAF, NEK11, AND S1K1

Abstract
The most prevalent subtype of non-small cell lung cancer (NSCLC) is
lung adenocarcinoma (LUAD), which is distinguished by a high
prevalence, a high death rate, and few available treatment choices.
Because of its intricate signalling network, LUAD necessitates
multiple-targeted therapy. Here, we evaluate Dabrafenib's
effectiveness as a novel B-RAF, NEK11, and S1K1 target drug in
LUAD, exploring a repurposing possibility for this selective B-RAF
inhibitor,
already
approved
for
malignant
melanoma.
Pharmacokinetic characteristics, molecular interactions, and toxicity
profiles of dabrafenib were evaluated using in silico methods.
SwissADME confirmed favourable drug-likeness, including
compliance with Lipinski's Rule of Five. Dabrafenib derivatives
showed high binding affinities against all three target proteins,
according to CB-Dock simulations. The OH-derivative had the highest
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Concepts and Statistical Approaches (2025)
binding affinity for NEK11 (−11.0 kcal/mol). ProTox-II predicted
minimal cytotoxicity and mutagenicity, along with moderate organ
specific toxicities. These findings support the hypothesis that
dabrafenib may serve as a novel adjuvant therapy to inhibit multiple
LUAD-related kinases.
Keywords: Molecular Docking; Dabrafenib; B-Raf; SIK1; NEK11; Lung
Adenocarcinoma