Structure-Based Design and Evaluation of Coumarin-Derived CDK4 Inhibitors for Non-Small Cell Lung Cancer: An Integrated Computational Study.

An Integrated Computational Workflow for Discovering Alkaloid-Derived Ligands of Cyclin-Dependent Kinase 2

Background/Objectives: Cyclin-dependent kinase 2 (CDK2) is a key regulator of cell-cycle progression and a potential anticancer target. This study aimed to identify alkaloid-derived CDK2 ligands using an integrated computational workflow and to obtain preliminary evidence of their effects on cancer-cell viability. Methods: Molecular docking with mVina and fast pulling of ligand (FPL) simulations were benchmarked using 20 experimentally characterized CDK2 inhibitors. A library of 2692 PubChem-derived alkaloids was screened, followed by ADMET evaluation, 100 ns molecular dynamics simulations, and FPL-based relative-affinity re-ranking. The three prioritized compounds were evaluated in HepG2 and HGC-27 cells using an MTT assay after 48 h of exposure. Results: Docking and FPL showed correlations with experimental affinity data of RDock = 0.549 ± 0.180 and RW = −0.676 ± 0.119, respectively. CID 636885, CID 46184320, and CID 101691758 were prioritized for detailed evaluation. All three compounds reduced cell viability, with lower IC50 values observed in HepG2 cells than in HGC-27 cells. CID 101691758 exhibited the highest growth-inhibitory activity among the tested compounds, with IC50 values of 15.37 ± 0.46 µg mL−1 in HepG2 cells and 52.64 ± 1.33 µg mL−1 in HGC-27 cells. Conclusions: The workflow identified three preliminary alkaloid hits, with CID 101691758 showing the most favorable combined computational and cell-viability profile. However, the MTT assay does not establish direct CDK2 inhibition or kinase selectivity. Biochemical CDK2 inhibition, target-engagement, and kinase-panel studies are therefore required.

Tetrazole–imidazole hybrid derivatives as potential EGFR tyrosine kinase inhibitors: design, synthesis and in silico evaluation with preliminary antiproliferative assessment

Comparative Structure-Based Molecular Docking Analysis of Clinically Approved CDK4/6 Inhibitors Targeting CDK6

Comparison in silico analysis provides structural insights into the binding behavior of clinical CDK4/6 inhibitors and may contribute to future optimization and development of CDK-targeted therapies.

Structure-Based In Silico Screening of PubChem Compounds for Potential Anti-Inflammatory and Anticancer Targets

C25, the pyrazolin derivative represents a novel multi-target ligand with potential applications as an anti-inflammatory, analgesic, and anti-neoplastic agent and highlights its promise as a lead scaffold for future drug development.

A multistage computational pipeline integrating ligand-based and structure-based screening with ADMET evaluation, molecular dynamic simulation and free energy calculations for the discovery of potential TNIK inhibitors.

This LBVS-SBVS-ADMET-MD pipeline effectively identified three promising TNIK inhibitors, providing a solid foundation for future experimental validation and potential development of targeted therapies for Wnt-driven malignancies.

Exploration of Natural Anti-Hepatocellular Carcinoma Compounds Targeting XIAP-BIR3 Using Molecular Docking, Conventional, and PaCS Molecular Dynamics

Mangostanol and 9-hydroxycalabaxanthone will be prioritized for in vitro/in vivo testing, underscoring the importance of a stepwise, structure-based approach to identify plant-based natural compounds targeting XIAP-BIR3.