In Silico Identification of 2,4-Diaminopyrimidine-Based Compounds as Potential CK1ε Inhibitors
Abstract
:1. Introduction
2. Results
2.1. Identification of Compounds Matching the Pharmacophore Model
2.2. Cheminformatic Analysis
2.3. Framework-Based Clustering
2.4. MD Simulations for Representative Compounds
2.5. Binding Free Energy for the CK1ε/Candidate Complexes
2.6. Analysis of the Binding Behavior
2.7. Assessment of the Group 5 Members
3. Discussion
4. Materials and Methods
4.1. Preparation of the CK1ε/REF 1–3 Complexes
4.2. Virtual Screening
4.3. MD Simulations
4.4. MD Analysis
4.5. MM/PBSA Calculation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CK1 | Casein kinase 1 |
CK1ε | Casein kinase 1 epsilon |
CK1δ | Casein kinase 1 delta |
IC50 | Half maximal inhibitory concentration |
FDA | Food and Drug Administration |
Ro5 | Lipinski’s rule of five |
ATP | Adenosine triphosphate |
PI3Kδ | Phosphoinositide 3-kinase-δ |
RMSD | Root-mean-square deviation |
HBD | Hydrogen bond donor |
HBA | Hydrogen bond acceptor |
B&M | Bemis and Murcko |
MD | Molecular dynamics |
RMSF | Root-mean-square fluctuation |
ns | Nanosecond |
MM/PBSA | Molecular Mechanics Poisson–Boltzmann Surface Area |
IE | Interaction entropy |
SMILES | Simplified Molecular Input Line Entry System |
ΔG | Change in Gibbs free energy |
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Sánchez-Álvarez, A.A.; Velasco-Velázquez, M.A.; Cordova-Bahena, L. In Silico Identification of 2,4-Diaminopyrimidine-Based Compounds as Potential CK1ε Inhibitors. Pharmaceuticals 2025, 18, 741. https://doi.org/10.3390/ph18050741
Sánchez-Álvarez AA, Velasco-Velázquez MA, Cordova-Bahena L. In Silico Identification of 2,4-Diaminopyrimidine-Based Compounds as Potential CK1ε Inhibitors. Pharmaceuticals. 2025; 18(5):741. https://doi.org/10.3390/ph18050741
Chicago/Turabian StyleSánchez-Álvarez, Axel A., Marco A. Velasco-Velázquez, and Luis Cordova-Bahena. 2025. "In Silico Identification of 2,4-Diaminopyrimidine-Based Compounds as Potential CK1ε Inhibitors" Pharmaceuticals 18, no. 5: 741. https://doi.org/10.3390/ph18050741
APA StyleSánchez-Álvarez, A. A., Velasco-Velázquez, M. A., & Cordova-Bahena, L. (2025). In Silico Identification of 2,4-Diaminopyrimidine-Based Compounds as Potential CK1ε Inhibitors. Pharmaceuticals, 18(5), 741. https://doi.org/10.3390/ph18050741