Multiscale Computational and Pharmacophore-Based Screening of ALK Inhibitors with Experimental Validation
Abstract
1. Introduction
2. Results
2.1. Pharmacophore Modeling Results
2.2. Optimal Pharmacophore Model Validation Results
2.3. Screening Results Based on the Optimal Pharmacophore Model
2.4. PAINS Filtering and ADMET Prediction Results
2.5. Activity Validation Results
2.6. Molecular Docking Results
2.7. Molecular Dynamics Simulation Results
3. Discussion
4. Materials and Methods
4.1. Database Selection and Ligand Conformation Optimization
4.2. Pharmacophore Modeling
4.3. Pharmacophore Model Validation
4.4. PAINS Filtering and ADMET Prediction
4.5. Molecular Docking
4.6. Activity Validation
4.7. Molecular Dynamics Simulation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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NO | IC50 Values (μM) |
---|---|
A549 | |
F1739-0081 | 261.7 |
F2571-0016 | >500 |
Ceritinib | 33.85 |
Lorlatinib | 265.6 |
Energy Component | Native Ligand (kcal/mol) | F1739-0081 (kcal/mol) | F2571-0016 (kcal/mol) |
---|---|---|---|
ΔEvdW | −61.25 | −52.01 | −50.50 |
ΔEele | −29.06 | −6.80 | −15.55 |
ΔEpolar | 50.82 | 22.36 | 37.66 |
ΔEnonpolar | −7.56 | −6.23 | −6.87 |
ΔGgas | −90.31 | −58.81 | −66.05 |
ΔGsolv | 43.26 | 16.13 | 30.80 |
ΔGMMGBSA | −47.05 | −42.68 | −35.26 |
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Zhang, Y.-K.; Tong, J.-B.; Sun, Y.; Zeng, Y.-R. Multiscale Computational and Pharmacophore-Based Screening of ALK Inhibitors with Experimental Validation. Pharmaceuticals 2025, 18, 1207. https://doi.org/10.3390/ph18081207
Zhang Y-K, Tong J-B, Sun Y, Zeng Y-R. Multiscale Computational and Pharmacophore-Based Screening of ALK Inhibitors with Experimental Validation. Pharmaceuticals. 2025; 18(8):1207. https://doi.org/10.3390/ph18081207
Chicago/Turabian StyleZhang, Ya-Kun, Jian-Bo Tong, Yue Sun, and Yan-Rong Zeng. 2025. "Multiscale Computational and Pharmacophore-Based Screening of ALK Inhibitors with Experimental Validation" Pharmaceuticals 18, no. 8: 1207. https://doi.org/10.3390/ph18081207
APA StyleZhang, Y.-K., Tong, J.-B., Sun, Y., & Zeng, Y.-R. (2025). Multiscale Computational and Pharmacophore-Based Screening of ALK Inhibitors with Experimental Validation. Pharmaceuticals, 18(8), 1207. https://doi.org/10.3390/ph18081207